Explore FREE downloadable educational materials.
What is the history of COVID-19 vaccine use in America?
Immediately after the January 30, 2020 WHO declaration that a novel coronavirus (SARS-CoV-2) outbreak in China posed a “public health emergency of international concern,” the Gates Foundation and World Health Organization (WHO) issued press releases informing the world that experimental coronavirus vaccines already in development would be put on a fast track to licensure for global use.
A research and development plan published by WHO stated there was an “urgent need” to fill in scientific knowledge gaps about the “basic biology” of COVID-19 illness and clinical evolution of COVID-19 and its epidemiology, as well as the need to develop appropriate animal models for research because some previous SARS and MERS vaccine studies in animals showed enhanced respiratory disease can occur in vaccinated animals after exposure to the live virus.
For the past two decades, coronavirus vaccine research has been hampered by one consistent vaccine adverse outcome in particular - paradoxical immune enhancement or disease enhancement. This outcome has not only been observed in SARS-CoV-1 and MERS-CoV vaccines, but also with vaccines using formalin-inactivation for measles (this vaccine was withdrawn in 1967) and respiratory syncytial virus (RSV) vaccines. Disease enhancement has also been observed with the live tetravalent dengue vaccine, Dengvaxia.
Vaccine induced disease enhancement occurs when the vaccine primes detrimental T cell response or antibodies in the recipient and increases the risk for infection or severe disease. This means that a vaccinated person may seem fine until they contract the illness, but the excess non-neutralizing antibodies not only fail to protect the person from infection but actually make it easier for the virus to infect cells and cause damage and, as a result, the disease is much more severe than it would have otherwise been.
By mid-March and early April 2020, the WHO, National Institutes of Health universities, and global pharmaceutical corporations had announced development of more than 50 experimental COVID-19 vaccines.
Responding to the call by public health officials to lockdown the U.S. with in-home quarantines, Congress passed the CARES Act signed into law on March 27, 2020 that would cost American taxpayers over two trillion dollars. This federal legislation included $27 billion for development of COVID-19 vaccines, drug therapies and purchase of pandemic medical supplies. The legislation, however, did not include a cap placed on how much money drug companies could charge and profits they could make on the COVID-19 vaccines and drug therapies they develop with the use of money from the government.
On March 30, 2020, the HHS Assistant Secretary of Preparedness and Response announced that the government was taking steps to “speed the development and manufacturing of vaccines to prevent COVID-19.”
The Biomedical Advanced Research and Development Authority (BARDA) was created by Congress in 2006 under the Pandemic and All Hazards Preparedness Act, legislation that has given billions of dollars to DHHS since then to develop “bioterrorism” and pandemic influenza vaccines. That federal legislation also removed all civil liability from pharmaceutical companies for injuries and deaths caused by vaccines and drugs manufactured in response to declared public health emergencies, such as pandemics.
Johnson & Johnson issued a press release on March 30, 2020, stating that BARDA had awarded Janssen Pharmaceutical Companies $1 billion to establish new U.S. vaccine manufacturing capabilities and additional production capacity outside the U.S to produce a global supply of more than 1 billion doses of the COVID-19 vaccine.
According to a March 30, 2020 Reuters report, Moderna, Inc. “also signed a deal with the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services. The arrangements were part of the federal government’s effort to encourage drugmakers to be able to produce massive amounts of COVID-19 vaccines even before any are proven to work.”
In May 2020, former President Donald Trump formally announced the framework and leadership of “Operation Warp Speed”, a private-public partnership aimed at making a COVID-19 vaccine available to the public by January of 2021. Trump appointed venture capitalist and former Chairman of Global Research and Development and Chairman of Global Vaccines at GlaxoSmithKline Dr. Moncef Slaoui as chief advisor on vaccine development. General Gustave F. Perna, the U.S. army’s four-star general responsible for global supply chain and materiel and installation readiness for the U.S. Army, was selected as chief operating officer and charged with COVID-19 vaccine distribution.
"President Trump's vision for a vaccine by January 2021 will be one of the greatest scientific and humanitarian accomplishments in history, and this is the team that can get it done," said HHS Secretary Alex Azar. "Dr. Slaoui and General Perna are ideal leaders for this unprecedented effort to get vaccines, therapeutics, and diagnostics to American patients much faster than ever before. Since January, America's scientists and innovators have been working day and night on this national effort. President Trump has refused to accept business-as-usual timelines for vaccines and other essential tools, and instead has insisted that America, and the world, needs answers faster. Under the President's leadership, his administration and American industry will squeeze every last inefficiency out of the process and pour every resource we can into this effort."
On June 30, 2020, the U.S. Food and Drug Administration (FDA) announced that a COVID-19 vaccine would only receive approval if it were at least 50 percent more effective than a placebo at either preventing infection or reducing illness severity.
The FDA released its guidance for industry regarding EUA approval for COVID-19 vaccines on October 6, 2020, and stated that they would be requiring that at least half of all Phase 3 clinical trial participants be followed for at least two months following administration of the second vaccine dose. The FDA also requested that vaccine makers submit information on a minimum of five cases of severe COVID-19 disease among individuals who received the placebo.
Under EUA authority, the FDA Commissioner may permit “unapproved medical products or unapproved uses of approved medical products to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by CBRN (CBRN = chemical, biological, radiological, nuclear) threat agents when there are no adequate, approved, and available alternatives.”
On October 22, 2020, the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) met to discuss COVID-19 vaccine safety and efficacy, and included groups representing ethnic and racial minorities. VRBPAC is comprised of non-FDA “experts” whose charge is to provide “advice to the Agency regarding the safety and efficacy of the vaccine for the proposed indication.”
Safety concerns dominated much of the meeting and several committee members expressed worry that the median two-month safety monitoring period appeared to be “arbitrary”. Additionally, if EUA approval was granted, there was concern that placebo control groups and blinding of the Phase 3 trials would be halted immediately and additional vital data would be lost.
A presentation on vaccine hesitancy by the Reagan-Udall Foundation for the Food and Drug Administration, a nonprofit established by Congress to advance the FDA’s overall mission, reported on the public’s concern over the speed of vaccine development and their overall distrust of the healthcare system and of government. Several committee members stated that allowing a COVID-19 vaccine to be approved under EUA would only increase vaccine safety concerns.
Concerns that minority populations were under-represented in clinical trials were discussed, however, Dr. Doran Fink of the FDA's Office of Vaccines Research and Review stated that while under-representation was not ideal, this would not cause the vaccine to be restricted for use in this demographic. Vaccine hesitancy among racial and ethnic minorities was also highlighted and attributed to past historical experiments that have resulted in mistrust of government and health officials.
COVID-19 vaccine efficacy discussions included a presentation by Dr. Hilary Marston, of the National Institutes of Health, who recommended that the FDA require at least a 60 percent efficacy rate for any approved COVID-19 vaccine.
Several committee members expressed concern that the FDA had allowed vaccine manufacturers to use broad definitions of COVID-19 disease as their primary endpoint criteria. Concerns included the potential that a vaccine that showed protection against mild disease could be licensed even though the product did not reduce hospitalizations or deaths.
VRBPAC Committee members also did not unanimously support the idea of allowing data from adult vaccine trials to be used to measure vaccine efficacy for children. VRBPAC Chair, Dr. Arnold Monto cautioned that due to differing immune responses and the potential risk of Multisystem Inflammatory Syndrome in Children (MIS-C), standard bridging of data may be inappropriate.
Additional VRBPAC meetings for each vaccine candidate approval or EUA was promised by the FDA, however, the FDA is not required to follow any recommendations made by their federal committee.
Despite previously stating that they were “committed to use an advisory committee composed of independent experts to ensure deliberations about authorization or licensure are transparent for the public” the FDA declined to hold a VRBPAC meeting prior to granting a license to BioNTech for its mRNA COVID-19 vaccine. In the Summary Basis for Regulatory Action Document published to support approval of Comirnaty, the Pfizer-BioNTech mRNA COVID-19 vaccine, the FDA reported that it “did not refer this application to the VRBPAC because our review of the information submitted to this BLA did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.”
Drug companies and government agencies racing to be the first to license a COVID-19 vaccine, began using different technology platforms to create experimental vaccines: inactivated virus, attenuated virus, recombinant protein subunit, virus-like particle, DNA, RNA and replicating and non-replicating viral vector. Traditional viral vaccines contain attenuated or inactivated viruses or protein subunits in addition to adjuvants, such as aluminum, to stimulate an immune response that produces artificial immunity. For the past two decades, researchers have been experimenting with new technology platforms, notably ones that introduce foreign DNA and RNA directly into the body’s cells for the purpose of developing experimental vaccines for SARS, MERS, HIV and other diseases.
Gene-based vaccines, which include DNA and mRNA types, encode for a specific viral protein from a pathogen - such as the spike protein for the SARS-CoV-2 virus. The genetic encoding instructs cells in the vaccine recipient to produce antigens that stimulate the immune system to produce antibodies specific to the antigen, without the recipient becoming infected by the pathogen that causes the disease. Compared to traditional vaccines, nucleic acid (genetic) vaccines are inexpensive and easier to manufacture because they consist only of DNA or RNA, which is taken up and translated into protein by host cells.
Messenger RNA (mRNA) vaccines inject human cells with mRNA, usually within lipid nanoparticles, to stimulate cells in the body to become manufacturers of viral proteins. In March 2020, a virologist at Imperial College London told Chemistry World that one advantage of using mRNA technology to make vaccines for humans is that, “Rather than generating proteins in a manufacturing plant and purifying them, you are getting the muscle to do the job and make the protein itself.”
While traditional vaccines typically work with a person’s acquired immune system (immunity gained from exposure to pathogens), COVID-19 mRNA vaccines also have the potential to trigger an immune response from a person’s innate immune system, or the immunity we are born with. However, there are many unknowns, such as length of immunity provided by COVID-19 mRNA vaccines, whether or not the correct viral proteins have been chosen, and the frequency and severity of vaccine reactions and disease enhancement.
Moderna COVID-19 Vaccine
The National Institute of Allergy and Infectious Diseases (NIAID) headed by Dr. Anthony Fauci issued a press release on March 16, 2020 announcing that a Phase 1 human clinical trial conducted by Kaiser Permanente Washington Health Research Institute in Seattle had begun to evaluate an experimental mRNA vaccine for COVID-19 (mRNA-1273) co-developed by NIAID scientists and scientists at Moderna, Inc, based in Cambridge, Massachusetts. The Coalition for Epidemic Preparedness (CEPI) helped fund the manufacturing of the vaccine for the Phase 1 clinical trial.
Moderna and NIAID began conducting human trials of the experimental mRNA-1273 COVID-19 vaccine prior to first conducting pre-clinical animal trials, which has been an important and customary part of vaccine development and testing process. On March 30, 2020, Moderna stated that its COVID-19 vaccine might be ready for emergency use in certain individuals, including healthcare workers, by the fall of 2020.
“The Company further reported that while a commercially-available vaccine is not likely to be available for at least 12-18 months, it is possible that under emergency use, a vaccine could be available to some people, possibly including healthcare professionals, in the fall of 2020. Any emergency use would be subject to authorization by the appropriate regulatory agencies, based on the emergence of clinical data for mRNA-1273 that would support use of the vaccine prior to licensure.”
Although neither DNA or mRNA vaccines had been tested in large-scale clinical trials, an April 3, 2020 article in Chemical and Engineering News highlighted the breakneck speed at which COVID-19 vaccines “are moving new technologies from the computer and into the clinic at an unprecedented rate.” What should be separate pre-licensure phases for proving safety and effectiveness - preclinical animal models, clinical testing, and manufacturing – were now “happening all at once.”
Moderna announced on May 18, 2020, that Phase 1 human clinical trials of its experimental COVID-19 vaccine showed positive results, with eight of the 45 healthy adult volunteer trial subjects developing antibodies that may provide protection against the SARS-CoV-2 virus.
The company also reported that four participants suffered Grade 3 vaccine reactions. Of the four participants who experienced Grade 3 reactions, three had received the 250-µg dose level and one had received the 100-µg dose level. The U.S. Department of Health and Human Services (HHS) describes a Grade 3 adverse event as
“severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care” such as “bathing, dressing and undressing, feeding self, using the toilet, taking medications.”
On July 27, 2020, National Institute of Allergy and Infectious Diseases (NIAID) announced that Phase 3 clinical trials of the Moderna COVID-19 vaccine had begun. The vaccine, a joint venture between Moderna, Inc., and the NIAID, part of the National Institutes of Health (NIH), was expected to enroll 30,000 healthy COVID-19-negative adults at 89 clinical test sites.
According to NIAID, study participants would be randomly assigned 1:1 to receive either two doses of the 100- µg experimental mRNA COVID-19 vaccine or two normal saline placebo doses. NIAID officials reported that the study’s primary goal was to evaluate vaccine safety and whether two vaccine doses could prevent symptoms of COVID-19. Additional secondary goals included evaluation of the vaccine’s ability to prevent severe COVID-19 disease or death, and the effectiveness of a single vaccine dose in preventing symptomatic COVID-19.
Moderna COVID-19 Vaccine EUA
In the U.S., Moderna’s mRNA COVID-19 vaccine Phase 3 clinical trials initially stalled due to the inability by company officials to recruit enough minority volunteers – a requirement of the FDA for any vaccine maker seeking Emergency Use Authorization (EUA) for its product. Health officials blamed past unethical and immoral medical experiments that targeted minority populations and not employing people of color to recruit minority clinical trial volunteers. However, on October 22, 2020, Moderna reported that it had completed enrollment of trial participants and had recruited 11,000 participants from ethnically diverse communities and participants between 18 and 65 years of age with underlying conditions.
On November 16, 2020, Moderna announced, that its experimental mRNA vaccine candidate showed a 94.5 percent efficacy against COVID-19. Company officials reported that their first interim results found a total of 95 COVID-19 cases among trial participants, with 90 cases in the placebo group and five in the vaccine group. According to Moderna, no severe cases of COVID-19 occurred among the vaccine recipients while 11 severe cases occurred in the placebo cases.
On December 18, 2020, the FDA issued an EUA for Moderna’s mRNA COVID-19 Vaccine for use in persons 18 years of age and older.
Anaphylaxis following vaccination with Moderna’s COVID-19 vaccine were also reported within days of the EUA approval. According to a report published by the CDC, between December 21, 2020 and January 10, 2021, 108 adverse events reports were identified as possible cases of severe allergic reaction to the vaccine. However, health officials considered only 10 cases to be anaphylaxis and reported that anaphylaxis occurred at a rate of 2.5 cases per million doses of Moderna COVID-19 vaccine administered.
Deaths following Moderna’s COVID-19 vaccination were also reported. On Jan. 5, 2021, baseball Hall of Famer Hank Aaron was administered the Moderna vaccine in an event that appeared to encourage others, especially African-Americans, to receive the vaccine. Seventeen days later, on January 22, 2021, Aaron died. Health officials have denied that the COVID-19 vaccine played a role in his death, and report that it was purely coincidental.
According to the federal vaccine adverse event reporting system (VAERS), as of the October 8, 2021 CDC data release there were a total of 309,258 reports submitted to VAERS associated with the experimental Moderna COVID-19 vaccine. Noted within these reports were 4,144 deaths; 5,498 permanent disabilities; 19,514 hospitalizations, 28,865 emergency room visits; and 4,585 life threatening events. Of the deaths reported in CDC’s October 8, 2021 data release, over 71 percent of overall reported deaths occurred in persons 65 years of age and older. Click for the most recent information on reports submitted to VAERS.
In early April 2021, Moderna CEO Stéphane Bancel reported that a third vaccine dose would be needed within one year. In an interview with Business Insider, Bancel stated that "I hope this summer to get the vaccine authorized for a boost so that we can help people getting boosted before the fall, so that we all have a normal fall and not a fall and winter like we just saw in the last 6 months." Moderna officials have reported that the vaccine is 90 percent effective six months after the second vaccine dose.
On July 8, 2021, the CDC and FDA announced that booster doses of COVID-19 vaccines were not required at this time and they, along with the National Institutes of Health (NIH), were actively engaged “in a science-based, rigorous process to consider whether or when a booster might be necessary.”
One month later, however, the FDA authorized use of a third dose of the Moderna COVID-19 vaccine in persons with certain immunosuppressive conditions, such as solid organ transplant recipients and individuals with similar conditions.
On August 18, 2021, Health and Human Services (HHS) announced a plan to begin administration of COVID-19 mRNA booster doses beginning the week of September 20, 2021. Public health officials recommended that the third dose be administered eight months following receipt of the second COVID-19 booster dose. Leading health officials, however, have reported that review of the application to support the use of a third Moderna vaccine dose would likely not be completed prior to the White House’s September 20th timeline to begin administration of the additional dose. According to health officials, data submitted to the FDA as of September 1, 2021 was “found inadequate and needs strengthening.”
In early May 2021, Moderna reported that the vaccine was 96 percent effective in adolescents between 12 and 17 years of age and that the company was planning to submit data for full FDA approval by the end of the month. As of October 16, 2021, the vaccine is only authorized for use in persons 18 years of age and older.
Moderna Vaccine Contamination Concerns
In late August 2021, Japanese health officials announced that it had suspended the use of 1.63 million Moderna mRNA vaccine doses after contaminants were noted in certain vials. These contaminants were reported to be stainless steel particles that were attributed to the manufacturing process. Company officials from Moderna along with representatives from Takeda Pharmaceuticals, the company that distributes the vaccine for use in Japan, reported that they did not believe that the stainless-steel contaminants would cause adverse health problems. Company officials reported that the particles were likely caused by friction between metal in the machinery used to place the stoppers on the vaccine vials.
Three deaths following receipt of the contaminated vaccines have been reported by Japanese health officials as of September 7, 2021. The deaths, however, are currently considered coincidental and unrelated to vaccination.
On September 7, 2021, Japan has stopped use of the Moderna vaccine and have announced plans to begin use of the Novavax COVID-19 vaccine.
Profits from Moderna COVID-19 Vaccines
Profits from sales of the Moderna COVID-19 vaccine are expected to earn the company approximately $19.2 Billion dollars in 2021.
Another experimental mRNA COVID-19 vaccine developed in a partnership between U.S. based pharmaceutical giant Pfizer, and German drug maker BioNTech, began human trials in late April 2020 in Germany. In early May 2020, Phase 1 and Phase 2 clinical U.S. trials evaluated the safety, tolerability, immunogenicity and potential efficacy of four different SARS-CoV-2 mRNA vaccine candidates using a two-dose or single-dose schedule, at up to three different dose levels and in three age groups (18 to 55 years old, 65 to 85 years old and 18 to 85 years old).
Trial participants were expected to receive one of four vaccine candidates—BNT162a1, BNT162b1, BNT162b2, BNT162c2 or a placebo. Each vaccine candidate represented a different mRNA formulation and target antigen. Albert Bourla, CEO of Pfizer, stated that if one or two variations of the vaccine candidates appeared successful, human trials would expand to include thousands of participants by September 2020. Additionally, Bourla stated:
“If things go well, and we feel that the product is safe and efficacious, and the FDA [Food and Drug Administration and EMA [European Medicines Agency and other regulatory agencies feel the same, we will be able to deliver millions of doses in the October time frame.”
The Phase 1/2 trials involved 45 healthy adults between the ages of 18 and 55 years and over 50 percent of participants experienced adverse reactions. Two participants suffered severe reactions. A Grade 3 fever of over 101.3°F two days after vaccination was experienced by one adult and sleep disturbance one day after vaccination was experienced by another.
On July 27, 2020, Pfizer and BioNTech announced the beginning of Phase 2/3 global trials (except China) of their BNT162b2 vaccine candidate. This experimental vaccine would be a 30µg level dose administered in a 2-dose regimen. Company officials reported that trials would include up to 30,000 adults between 18 and 85 years of age and if successful, they would pursue regulatory approval of some form by October 2020. If approved, their plan was to supply up to 100 million doses globally by the end of 2020, and 1.3 billion doses by the end of 2021.
In mid-September, Pfizer and BioNTech reported that they had submitted an amended plan to the FDA to increase the number of trial participants to 44,000 and permit inclusion of individuals with chronic and stable Hepatitis B, Hepatitis C, and HIV as well as adolescents as young as 16 years of age. They also reported that trial participants were reporting mild-to-moderate adverse reactions which included headache, fatigue, chills, and muscle pain. Fevers, including high fevers, were also reported. Pfizer’s head of vaccine research and development stated that the data was being monitored by an independent monitoring committee that "has access to unblinded data so they would notify us if they have any safety concerns and have not done so to date."
Pfizer-BioNTech COVID-19 Vaccine EUA
On November 9, 2020, Pfizer-BioNTech issued a press release reporting that their experimental COVID-19 vaccine had an efficacy rate of over 90 percent “at 7 days after the second dose” in trial participants who had no prior history of SARS-CoV-2 infection. Pfizer-BioNTech applied for Emergency Use Authorization (EUA) approval from the FDA on November 20, 2020 and received EUA approval on December 11, 2020 for use in persons 16 years of age and older.
The experimental vaccine was previously granted EUA status in the U.K. on December 2, 2020 and within days of the vaccine’s initial roll-out, reports of anaphylaxis following vaccination began to surface. This prompted U.K. health officials to issue a warning against administration of the vaccine in persons with a previous history of anaphylaxis to any medicine or food.
Immediately following the FDA issuance of an EUA for Pfizer-BioNTech’s COVID-19 vaccines, reports of anaphylaxis began to appear in the U.S. media. Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, suggested that a chemical ingredient called polyethylene glycol (PEG)—a polymer derived from petroleum used as an excipient (a diluting agent) in both the BNT162b2 vaccine and Moderna’s COVID-19 vaccine known as mRNA-1273, was likely responsible for the severe reactions.
Between December 14 and 23, 2020, 21 cases of anaphylaxis were reported to the federal Vaccine Adverse Events Reporting System (VAERS), with 71 percent occurring within 15 minutes of vaccine administration. Of these cases, 17 reports were in persons with a past history of allergic reaction, including seven who had previously reported a history of anaphylaxis. Public health officials reported that anaphylaxis following Pfizer-BioNTech’s COVID-19 vaccine occurred at a rate of 11.1 cases per million doses administered.
In addition to reports of anaphylaxis, deaths following Pfizer-BioNTech’s vaccine administration were also reported to VAERS. In January 2021, a 56-year-old obstetrician developed a bleeding disorder within 72 hours of vaccination, and died 16 days later of a stroke.
As of the October 8, 2021 CDC release of data, reports submitted to VAERS for the Pfizer-BioNTech’s experimental COVID-19 vaccine for serious vaccine adverse events were 426,948. Noted within these reports were 11,350 deaths; 17,699 permanent disabilities; 54,335 hospitalizations; 52,875 emergency room visits; and 12,143 life threatening events. Of the reported deaths for this release of data, 50 percent of the deaths did not denote an age, with 40 percent occurring in persons 65 years of age and older. Click for the most recent information on reports submitted to VAERS.
In January 2021, health officials in Norway reported that they were investigating the deaths of 23 elderly individuals following vaccination with the Pfizer-BioNTech COVID-19 vaccine. The Norwegian Medicines Agency (NOMA) concluded that in 13 of the 23 deaths, common mRNA vaccine adverse reactions, such as diarrhea, fever, and nausea may have contributed to the deaths in the frail patients. Deaths following the Pfizer-BioNTech COVID-19 vaccine were also reported in Israel, Germany, Portugal and Switzerland.
In mid-December 2020, pharmacists administering the Pfizer-BioNTech COVID-19 vaccine discovered that vials contained six or even seven vaccine doses, instead of five – the amount listed on the product vial. The extra doses were attributed to overfill of the vials and dependent on the type of needle and syringe used to administer the vaccines. In January 2021, the FDA officially granted Pfizer’s request to update the EUA Fact Sheet to clarify that each vial contained six doses.
In order for all six vaccine doses to be extracted from the vial, special syringes known as low dead space syringes are required, which are in short supply. The lack of proper syringes caused controversy in Europe in January 2021 when it was revealed that Pfizer would be paid for six vaccine doses of the vaccine even though it was only possible to extract five doses from the vial. The U.S. government finalized a contract with Pfizer that would permit government officials to track which vaccine shipments came with dead space syringes and which did not. Shipments accompanied by dead space syringes would be counted as having six doses per vial, while those with regular syringes would count as having only five.
On May 10, 2021, the FDA expanded the EUA granted Pfizer/BioNTech to distribute its experimental mRNA vaccine in the U.S. to include administration to children as young as 12 years old and the CDC’s ACIP voted to approve its use in this population on May 12, 2021.
The approval for use in adolescents 12 to 15 years was based on a small clinical trial involving 2,260 teens, of which 1,131 received the vaccine and 1,129 received a saline placebo. According to the FDA’s Fact Sheet for Healthcare Providers Administering Vaccine:
“In a clinical study, adverse reaction in adolescents 12 through 15 years of age included pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), injection site redness (8.6%), lymphadenopathy (0.8%), and nausea (0.4%).”
During the clinical trial, nearly 11 percent of 12- to 15-year-olds experienced a severe or Grade 3 vaccine reaction, with one study participant experiencing a Grade 4 reaction of a fever of 40.4°C. Five adolescents who received the Pfizer vaccine experienced a serious adverse event (SAE) during the trial, however, none of these events were considered by clinical trial investigators to be related to vaccination.
On July 16, 2021, the FDA announced that it had accepted the Biologics License Application (BLA) from Pfizer requesting full licensure and had granted a priority review of the application. In early August 2021, the FDA announced that it was aiming to fully approve the Pfizer-BioNTech COVID-19 vaccine by Labor Day.
Pfizer-BioNTech COVID-19 Vaccine Approval
On August 23, 2021 the FDA licensed and granted EUA status to Comirnaty COVID-19 vaccine, an mRNA vaccine developed BioNTech, for use in persons 16 years of age and older. The FDA also stated that use of Comirnaty and the experimental Pfizer-BioNTech mRNA COVID-19 vaccine are interchangeable due to having the same formulation.
The FDA also stated that use of Comirnaty and the experimental Pfizer-BioNTech mRNA COVID-19 vaccine are interchangeable due to having the same formulation. However, the FDA also stated that the Pfizer-BioNTech experimental vaccine and the BLA approved Comirnaty were legally distinct, but did not disclose how and why the two vaccines are legally distinct. As of October 20, 2021 the FDA has now stated that the “vaccine has been known as the Pfizer-BioNTech COVID-19 Vaccine, and will now be marketed as Comirnaty”.
Following FDA approval, the CDC’s Advisory Committee on Immunization Practices (ACIP) recommended use of the 2-dose vaccine series in persons 16 years of age and older.
When a product receives a priority review designation by the FDA, the decision to take action on the application is usually done within 6 months. In the case of the Pfizer – BioNTech vaccine, the decision to grant full approval was completed in less than four months.
Prior to granting approval of Comirnaty, the FDA declined to hold a Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting despite previously stating that they were “committed to use an advisory committee composed of independent experts to ensure deliberations about authorization or licensure are transparent for the public.”
In June 2021, a group comprised of international scientists, clinicians, and patient advocate organizations formally submitted a Citizen Petition with the FDA and requested that the regulatory agency delay full approval of COVID-19 vaccines. In their petition, the Coalition Advocating for Adequately Licensed Medicines (CAALM) appealed to the agency to slow down the approval process to ensure that the scientific data was thoroughly assessed. In their petition, the group detailed safety and efficacy criteria that the FDA needed to provide prior to full licensure. These included:
- Completion of a minimum follow-up for at least two years of individuals who participated in the clinical trials, including trials that are no longer placebo controlled;
- Ensuring that evidence is clear that the benefits of vaccination outweigh the risks in specific populations such as in persons with previous SARS-CoV-2 infection, pregnant women, nursing women, infants, children, adolescents as well as in older adults, persons with immunosuppressive disorders, blood disorders, and those with cancer:
- Requiring a complete safety review of the spike proteins being produced by the body after vaccination, as well as the spike proteins’ full distribution within the body, the pharmacokinetics, and tissue specific toxicity;
- Completion of vaccine distribution studies at the injection site and the impact of the mRNA technologies in the tissues of the body;
- A complete assessment and review of all severe adverse events and deaths reported to VAERS and other global vaccine safety monitoring systems following COVID-19 vaccination;
- Full assessment of the safety of the vaccine in persons receiving more than two vaccine doses;
- Include experts in gene therapy and delivery in VRBPAC meetings due to the significant differences between gene-based vaccines and traditional vaccines;
- Ensure that individuals involved in reviewing clinical data submitted to support full approval are free of conflicts of interest with vaccine makers.
The FDA, however, disregarded the request made by the petitioners, and granted full approval of the Pfizer-BioNTech mRNA COVID-19 vaccine in persons 16 years of age and older without addressing the concerns expressed by CAALM.
Additionally, in the Summary Basis for Regulatory Action Document published to support approval of Comirnaty, the FDA reported that it “did not refer this application to the VRBPAC because our review of the information submitted to this BLA did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.”
The FDA has also determined that Comirnaty is interchangeable with the Pfizer-BioNTech mRNA vaccine, which also has an EUA status. This means that both vaccines can be used interchangeably in individuals 12 years and older and as a third dose in persons who are immunocompromised. Following FDA approval, ACIP voted to recommend the 2-dose vaccine series for use in all persons 16 years of age and older.
Pfizer-BioNTech mRNA COVID-19 Booster doses
In the spring of 2021 Pfizer CEO Albert Bourla reported that a third vaccine dose would likely be needed within 12 months, and annual shots might also be necessary. On July 8, 2021, the FDA and CDC announced that they were not recommending booster doses, but reported that they were monitoring data. The Federal agencies also stated that they “are prepared for booster doses if and when the science demonstrates that they are needed.”
One month later, however, the FDA authorized use of a third dose of the Pfizer-BioNTech COVID-19 vaccine in persons with certain immunosuppressive conditions, such as solid organ transplant recipients and individuals with similar conditions.
On August 18, 2021, Health and Human Services (HHS) announced a plan to begin administration of COVID-19 mRNA booster doses beginning the week of September 20, 2021. Public health officials stated that they would be recommending that the third dose be administered eight months following receipt of the second COVID-19 booster dose.
Not all public health officials agreed with the booster dose recommendation. Following the White House’s announcement on booster doses, two senior FDA vaccine officials announced their resignations. Their decision to leave the agency was reported to be related to the White House’s announcement on booster doses ahead of the FDA’s completion of review on the data to support this recommendation.
On September 13, 2021, the Lancet published a report authored by 18 scientists, including several from the World Health Organization and the FDA, against a broad recommendation of mRNA booster doses in the general population. The authors expressed concerns that the introduction of booster doses too soon or too frequently could result in serious immune-related adverse events and may deter acceptance of the use of COVID-19 and other vaccines. While the authors reported that certain populations, such as those with immunosuppressive conditions, may benefit from a booster dose, they indicated that ensuring a primary vaccine series in previously unvaccinated individuals would save more lives than boosting previously vaccinated populations.
On September 17, 2021, the FDA’s Vaccine and Related Biological Products Advisory Committee (VRBPAC) voted to authorize use of a third booster dose of the Pfizer-BioNTech mRNA COVID-19 vaccine under EUA in persons 65 years of age and older as well as those who are at high risk of severe illness. The booster dose for this population is recommended at 6 months following administration of the second dose.
The FDA amended the Pfizer-BioNTech EUA on September 22, 2021 and authorized a booster dose in all persons 65 years and older, in individuals 50 through 64 years at high risk for COVID-19, and in persons 18 through 64 “whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.”
While the CDC’s ACIP voted on September 23, 2021 to recommend booster doses in all persons 65 and older, in persons 50 through 64 years with pre-existing health conditions that put them at increased risk from COVID-19 infection, and in persons 18 through 49 who are at risk of infection due to pre-existing health conditions if the individual believes that they need one, they voted against recommending a booster dose for all persons 18 through 64 years whose living or employment situation places them at high risk for COVID-19 infection. CDC Director Dr. Rochelle Walensky, however, overruled ACIP and went ahead and issued a recommendation for a booster dose of Pfizer-BioNTech COVID-19 vaccine in all persons 18 and older who work or live in high-risk settings.
Pfizer-BioNTech mRNA COVID-19 Vaccine Profits
In February 2021, Pfizer reported that their expected 2021 earnings from COVID-19 sales were estimated at $15 billion dollars. However, as of late July 2021, Pfizer had increased its earnings estimate from sales of its COVID-19 vaccine to $33.5 Billion. The company also increased the price per dose of the vaccine from $19.50 to $24.00.
Pfizer-BioNTech mRNA COVID-19 Vaccine Contamination Concerns
In early September 2021, Japanese health officials reported that “floating matter” was found in five unused vials of COVID-19 vaccines belonging to the same vaccine lot. Vaccines from the same lot continued to be administered after being visually inspected. Pfizer company officials responded by stating that the material was probably undissolved vaccine ingredients and would not impact the safety or efficacy of the product. Additionally, Pfizer also reported that as of September 5, 2021, floating matter had been reported in at least 95 vials.
Heart Inflammation following mRNA vaccination
In May 2021, Israeli health officials reported a possible link between the Pfizer COVID-19 vaccine and myocarditis after reporting that 62 cases had been reported following vaccination. Of these cases, 56 had occurred following the second shot, and most had involved persons 30 years of age and younger. A Pfizer spokesperson, however, stated that a causal link had not been established and that they had not observed a higher rate of myocarditis post-vaccination then what would have been expected in the overall population.
On May 17, 2021, the Advisory Committee on Immunization Practices (ACIP) COVID-19 Vaccine Safety Technical (VaST) Work Group met and reviewed information on myocarditis following mRNA vaccines. VaST reported that most of the cases had occurred in teens and young adults, and more cases had occurred in males. Additionally, there were more cases reported after the second vaccine dose, and most occurred on average within four days of vaccination. Members of VaST reported that few cases had been reported but that information on myocarditis following COVID-19 vaccination should be given to vaccine providers.
Reports of myocarditis and pericarditis following mRNA vaccines continued to increase and on June 11, 2021, the CDC scheduled an emergency ACIP meeting for June 18, 2021 to discuss the higher than expected number of cases. A total of 301 cases following Moderna vaccination and 488 cases following Pfizer vaccination had been reported at the time the meeting was scheduled.
The meeting, however, was postponed due to the newly created Juneteenth National Independence Day holiday, with the CDC announcing that it would discuss concerns the following week at the regularly scheduled June ACIP meeting. By the June 23, 2021 meeting, CDC officials reported that through June 11, 2021, 1,226 cases of myocarditis/pericarditis had been reported to VAERS, with 791 occurring after Pfizer vaccination and 435 after Moderna vaccination. Most cases were reported in males, and most occurred following the second dose.
In the data presented during the June 23, 2021, the CDC reported that in females between the age of 12 and 17 years, after the second dose, the case rate of myocarditis/ pericarditis was 9.1 per million doses administered. In males 12 to 17 years of age, however, the rate after the second vaccine dose was 66.7 per million doses. Cases among females 18 to 24 years old after dose two were reported at 5.5 per million, while after dose two, males of the same age range were affected at a rate of 56.3 per million doses. Most cases of myocarditis/pericarditis resulted in hospitalization, and while most were reported as being resolved, the long-term health outcomes were reported to be unknown.
The CDC, however, declined to pause use or make changes to the vaccine recommendations, as they reported the benefits to vaccination outweighed the risk. Additionally, they stated that persons with a history of myocarditis and pericarditis could still receive an mRNA vaccine and persons who developed pericarditis after the first mRNA vaccine dose could receive the second dose after symptoms resolved. The CDC also advised that individuals who developed myocarditis after the first dose could consider receiving a second dose under certain circumstances. No data to support this recommendation was provided.
The FDA reported that the Moderna and Pfizer Fact Sheets would be updated to include a warning of the risk of myocarditis/pericarditis.
A study of myocarditis after mRNA vaccines on members of the military has found a higher than expected number of cases following vaccination. Additional studies have also associated mRNA vaccines with heart inflammation, with researchers reporting the need for further investigation.
A real-world study on the Pfizer-BioNTech vaccine conducted by Israeli scientists found that vaccination most likely caused myocarditis in one to five individuals per 100,000 who would not have developed the condition. Their study also found that young males were at highest risk for developing the condition.
A preprint study posted on September 8, 2021 on MedRxiv found that teenage boys were most likely to be hospitalized for heart inflammation from mRNA COVID-19 vaccines than from COVID-19 disease. This study was based on filed reports to the Vaccine Adverse Events Reporting System (VAERS) between January 1 and June 18, 2021 in teens between the ages of 12 and 17 years of age. Researchers concluded that:
“For boys with no underlying health conditions, the chance of either cardiac adverse event (CAE), or hospitalization for CAE, after their second dose of mRNA vaccination are considerably higher than their 120-day risk of COVID-19 hospitalization, even at times of peak disease prevalence. The long-term consequences of this vaccine-associated cardiac inflammation are not yet fully defined and should be studied.”
Study authors suggested that the U.S. could consider a policy change that would delay vaccination in healthy children who have a low risk of developing severe COVID-19 illness or recommend only a single vaccine dose of mRNA vaccine.
According to the CDC, as of October 6, 2021, 1,640 reports of myocarditis and pericarditis following COVID-19 mRNA vaccines had been reported to VAERS among persons 30 years of age and younger. Most cases have occurred in teenage boys.
Both mRNA COVID-19 vaccines are authorized to be given intramuscularly(IM) in a two-dose series. Doses of the Pfizer-BioNTech vaccine should be administered 21 days apart, while doses of the Moderna vaccine are to be given 28 days apart. In early January 2021, following reports in the media of alternative vaccine schedules which included giving a single vaccine dose, giving half doses, and using vaccine brands interchangeably, the FDA issued a press release to emphasize the need for clinicians to follow the authorized EUA dosing schedules. Agency officials reported that without clinical data to support alternative dosing schedules, the public could be put at risk and might ultimately undermine efforts to protect people against COVID-19.
In contrast, U.K. health officials announced in early January 2021 that it was prioritizing first dose administration to as many people as possible, and delaying the booster dose until more vaccines became available. The U.K. Joint Committee on Vaccination and Immunization (JCVI) stated that:
“Given the high level of protection afforded by the first dose, models suggest that initially vaccinating a greater number of people with a single dose will prevent more deaths and hospitalizations than vaccinating a smaller number of people with two doses.”
The University of Oxford is currently studying the use of different combinations of COVID-19 vaccines in persons 50 years of age and older. As of October 16, 2021, studies were ongoing to evaluate the safety and effectiveness of using a different COVID-19 vaccine as the second vaccine dose. Vaccines involved in the clinical trials included Pfizer-BioNTech, Moderna, AstraZeneca, and Novavax. Preliminary results are expected by early summer 2021 but the study is expected to continue for at least one year.
According to a study published in The Lancet on May 12, 2021, adults 50 years and older who received a mixed dose combination of the Pfizer-BioNTech vaccine and the AstraZeneca COVID-19 vaccines experienced more mild and moderate side effects than those administered only one type of vaccine. Systemic reactions, especially fever, were significantly higher after the second vaccine dose in persons who received the AstraZeneca vaccine followed by a dose of the Pfizer-BioNTech vaccine when compared to persons who received two doses of the Pfizer-BioNTech vaccine. There were also more reports of joint and muscle pain, chills, malaise, fatigue, and headache after the second vaccine dose in person who received a mixed dose schedule.
In March 2020, Janssen/Johnson & Johnson announced that it had expanded its partnership with BARDA to reach its goal of providing one billion COVID-19 vaccine doses. Company officials reported that human trials of an experimental COVID-19 vaccine utilizing its AdVac® and PER.C6® technologies would likely begin in September 2020. The AdVac technology uses an adaptation of human Adenovirus 26 to transport the genetic code of the SARS-CoV-2 spike protein into the body to trigger an immune response. PER.C6 are proprietary cells owned by Janssen Pharmaceutical that were developed in 1985 from retinal cells of an 18-week-old aborted fetus.
The Janssen/Johnson & Johnson experimental COVID-19 vaccine entered Phase 2 trials in Spain in mid-September 2020. Clinical trials, however, were halted on October 12, 2020 after a participant developed an “unexplained illness.” Sources familiar with the event reported that a male in his 20’s had a stroke after receiving the experimental vaccine. Clinical trials in the U.S resumed in late October 2020.
On January 29, 2021, company officials reported that overall, their COVID-19 vaccine was 66 percent effective at preventing moderate to severe symptoms, 85 percent effective at severe illness, and 100 percent effective at preventing COVID-19-related hospitalizations and deaths.
Janssen/Johnson & Johnson COVID-19 Vaccine EUA
On February 27, 2021, the FDA issued an EUA for Janssen/Johnson & Johnson’s experimental vaccine for use in persons 18 years of age and older.
Common side effects reported after vaccine administration with the Janssen COVID-19 in clinical trials included injection site pain, headache, fatigue, myalgia, nausea, fever, injection site redness and swelling.
Serious adverse events reported after vaccine administration included severe pain in the injected arm, hives, hypersensitivity, deep vein thrombosis, pulmonary embolism, transverse sinus thrombosis, severe generalized weakness with fever and headache, tinnitus (ringing or buzzing noises in the ears) and seizures.
On April 13, 2021, the FDA and CDC paused use of the vaccine after serious blood clots were reported in women between the ages of 18 and 49. By April 23, 2021, 15 cases and 3 deaths had been associated with the rare blood clot disorder, now referred to by health officials as thrombosis with thrombocytopenia syndrome (TTS). All cases were reported in women, with 2 occurring in women over 50 years of age. The CDC’s Advisory Committee on Immunization Practices (ACIP) voted to resume full use of the vaccine in all persons 18 years of age and older on April 23, 2021, by a vote of 10 to 4 (with one voting member abstaining due to a conflict of interest). Those who voted against the recommendation expressed concern regarding the lack of warning on the risk of TTS in women under 50 years of age.
On April 23, 2021, the FDA updated the Janssen/Johnson & Johnson’s COVID-19 Fact Sheet and acknowledged that:
“Reports of adverse events following use of the Janssen COVID-19 Vaccine under emergency use authorization suggest an increased risk of thrombosis involving the cerebral venous sinuses and other sites (including but not limited to the large blood vessels of the abdomen and the veins of the lower extremities) combined with thrombocytopenia and with onset of symptoms approximately one to two weeks after vaccination. Most cases of thrombosis with thrombocytopenia reported following the Janssen COVID-19 Vaccine have occurred in females ages 18 through 49 years; some have been fatal. The clinical course of these events shares features with autoimmune heparin-induced thrombocytopenia. In individuals with suspected thrombosis with thrombocytopenia following the Janssen COVID-19 Vaccine, the use of heparin may be harmful and alternative treatments may be needed. Consultation with hematology specialists is strongly recommended.”
By May 7, 2021, there had been 28 cases of TTS and 3 deaths confirmed by the CDC to be related to the Johnson & Johnson/Janssen COVID-19 vaccine. Moreover, TTS has been reported in men and in women between 50 and 60, in addition to women between 18 and 49 years.
As of October 6, 2021, 47 cases of TTS following the Janssen/Johnson & Johnson COVID-19 vaccine had been confirmed by the CDC and FDA.
On July 12, 2021, the FDA announced that it would be issuing a warning that the Johnson & Johnson/Janssen COVID-19 vaccine could trigger Guillain-Barré syndrome (GBS). Health officials have reported 100 cases of GBS following vaccination, with 95 considered serious and requiring hospitalization, and one death. According to the FDA:
"Although the available evidence suggests an association between the Janssen vaccine and increased risk of GBS, it is insufficient to establish a causal relationship….Importantly, the FDA has evaluated the available information for the Janssen COVID-19 Vaccine and continues to find the known and potential benefits clearly outweigh the known and potential risks."
As of October 6, 2021, 228 cases of GBS following the Janssen/Johnson & Johnson COVID-19 had been identified in the VAERS data. According to the CDC, most cases occurred within 2 weeks of vaccination and among men, primarily those aged 50 and older.
In early September 2021, the European Medicines Agency reported that its Pharmacovigilance Risk Assessment Committee (PRAC) was investigating a link between the Johnson & Johnson/Janssen COVID-19 vaccine and venous thromboembolism (blood clots in the veins). According to PRAC, in the initial clinical trials of the vaccine, a higher rate of venous thromboembolism was noted in the vaccine group when compared to the placebo group. Additional data collected from two larger clinical trials were expected to be submitted to PRAC in advance of vaccine marketing authorization, to determine whether the condition was linked to vaccination.
In clinical trials, the vaccine was reported to be 66.9 percent effective in preventing moderate to severe COVID-19 occurring at least 14 days after vaccination and 66.1 percent effective in preventing moderate to severe COVID-19 occurring at least 28 days after vaccination.
Data is currently not available to determine how long the vaccine will provide protection, and there is no evidence that the vaccine prevents transmission of SARS-CoV-2 from person to person.
As of the October 8, 2021 CDC release of data, vaccine adverse events submitted to VAERS associated with the Johnson & Johnson/Janssen vaccine totaled 61,939, with 7,982 reports noted as serious. Included in these reports were 1,228 deaths; 1,574 permanent disabilities; 7,948 emergency room visits; and 5,659 hospitalizations. Click for the most current VAERS release data.
Johnson & Johnson/Janssen COVID-19 Vaccine Production Concerns
On March 31, 2021, The New York Times reported that vaccine ingredients were mixed up by employees at an Emergent BioSolutions plant in Baltimore, resulting in up to 15 million ruined Johnson & Johnson vaccine doses. The mistake, which was determined by federal investigators to be the result of “human error”, was caught before any doses were released for distribution. The Baltimore plant was enlisted by the federal government in 2020 to manufacture vaccines developed by both Johnson & Johnson and AstraZeneca. While these vaccines use similar technologies, their ingredients and manufacturing processes are not interchangeable. According to The New York Times, in February 2021, one or more workers erred in the production process that was not discovered by Johnson & Johnson quality control checks for several days.
This was not the first time that the Emergent BioSolutions Baltimore plant had been cited for errors. In April 2020, an FDA investigator had discovered that employees at the plant lacked adequate training, testing protocols were not being followed, records were not properly secured, and policies to ensure that mix-ups or contaminations would not occur were found to be inadequate. Despite these safety issues, the plant was awarded $628 million by the U.S. government and also secured deals worth more than $740 million with AstraZeneca and Johnson & Johnson to manufacture COVID-19 vaccines for both companies at the Baltimore site.
On April 20, 2021, the FDA cited the Baltimore Emergent BioSolutions plant for multiple quality control and sanitary issues, including their failure to adequately review and investigate the events that resulted in the manufacturing of 15 million botched Johnson & Johnson vaccine doses. Additionally, the FDA reported that they were not confident that previously released batches of the vaccines were not subject to cross-contamination. Unsanitary conditions at the plant included chipping paint from the walls in the hallways surrounding the manufacturing rooms, “brown residue” on walls, “black residue” and debris on the floor, and congested work areas. Plant employees were noted to be carrying unsealed bags containing medical waste and even “throwing unsealed bags of special medical waste into the service elevator accessing the warehouse corridor.”
Johnson & Johnson/Janssen COVID-19 Vaccine Profits
In mid-April 2021, Johnson & Johnson reported $100 million in first quarter earnings from its COVID-19 vaccine. Company officials have reported that annual vaccine doses will likely be needed for several years.
Johnson & Johnson/Janssen Booster Doses
On July 8, 2021, the CDC and FDA report that vaccine booster doses were not currently needed but they were continuing to review the data. However, one month later, in August 2021, a third dose of mRNA COVID-19 vaccine was recommended by the FDA in persons with immunosuppressive conditions such as solid organ transplant recipients. The recommendation did not include the use of a booster dose in immunocompromised individuals who received the Johnson & Johnson/Janssen COVID-19 vaccine.
As of September 27, 2021, the CDC is reporting that a booster dose of the Johnson & Johnson/Janssen COVID-19 vaccine will likely be needed and that more data on the safety and effectiveness of a booster dose is expected in the near future.
AstraZeneca-University of Oxford COVID-19 vaccine
A vaccine development team from the University of Oxford in the United Kingdom endeavored to make an experimental COVID-19 vaccine candidate by the end of the summer of 2020. On April 23, 2020, human trials of the ChAdOx1 nCoV-19 experimental vaccine using a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein began.
The University of Oxford reported that the initial clinical trials of ChAdOx1 nCoV-19 would involve 800 individuals. Half would receive the experimental vaccine while the other half would serve as the control group and receive a meningitis vaccine (MenACWY).
Preliminary results of the AstraZeneca’s Phase 1 and Phase 2 trials were published in July 2020 in The Lancet. This study involved 1,077 healthy adults between 18 and 55 years of age who were randomly given either the ChAdOx1 nCoV-19 vaccine (AZD1222) or the meningococcal conjugate (MenACWY) vaccine. Systemic and local reactions were more common in the trial group given the experimental COVID-19 vaccine, and a selection of participants from both groups received prophylactic paracetamol (acetaminophen) before vaccinations were administered.
In April 2020, Oxford University partnered with AstraZeneca to develop, manufacture, and distribute the ChAdOx1 nCoV-19 vaccine (now referred to as AZD1222) and U.S. Phase 3 clinical trials began in late August 2020. Their goal was to enroll 30,000 vaccine participants through 62 sites. On September 8, 2020, the pharmaceutical company announced that it was putting the trial on hold after a female participant in the U.K. developed transverse myelitis, a rare but serious neurological disorder, which causes inflammation of the spinal cord. This was the second time that AZD1222 vaccine trials were placed on hold. In July 2020, trials were paused after a woman developed multiple sclerosis; however, company officials reported that her diagnosis was not related to vaccination.
While clinical trials resumed quickly in several countries including Great Britain, Japan, South Africa, India, and Canada, trials in the U.S. remained on hold until October 23, 2020.
On October 1, 2020, the European Medicines Agency (EMA) stated that it had started reviewing AstraZeneca’s COVID-19 clinical trial data in real time, and anticipated that following approval, all adults in Britain could receive at least one vaccine dose within 6 months.
At the January 27, 2021 advisory committee meeting of the U.S. Centers for Disease Control (CDC), company officials from AstraZeneca reported that across the four studies, serious adverse events occurred in 168 participants, with 79 occurring among persons who received the experimental COVID-19 vaccine, and 89 among persons who received either the MenACWY vaccine or saline control. In total, 175 serious adverse events were reported; however, only four events were considered as possibly related to vaccination by clinical trial investigators. Company officials also reported that most solicited adverse events were mild to moderate and the majority resolved within a few days of vaccination.
The European Union approved the vaccine for use in individuals 18 years and older on January 29, 2021, despite limited data to support its effectiveness in adults over the age 55 years. The University of Oxford and AstraZeneca’s COVID-19 vaccine is estimated to have an efficacy of about 60 percent.
Health officials in South Africa have halted use of the AstraZeneca COVID-19 vaccine after it was found to be less than 25 percent effective against the B.1.351 variant, which is most common SARS-CoV-2 virus variant circulating in South Africa.
On March 12, 2021, CNN reported that while AstraZeneca, and UK and European regulators stated there was no evidence of this experimental COVID-19 vaccine causing blot clots, a number of countries had already suspended use of the vaccine. These countries included Denmark, Norway, Iceland, and Thailand. Other countries, like Austria and Italy chose instead to suspend specific batches of the vaccine, while Spain delayed rollout of the AstraZeneca vaccine.
The World Health Organization (WHO) issued a statement on March 19, 2021 stating that their Global Advisory Committee on Vaccine Safety reviewed data on the vaccine in relation to blood clots and low platelets after vaccination and concluded that the rates of these events are fewer than when they occur naturally in the generalized population. The WHO added and that these events would continue to be monitored.
Soon thereafter, Canadian health officials joined France and limited the vaccine’s use in persons under 55 years of age, stating “From what is known at this time, there is substantial uncertainty about the benefit of providing AstraZeneca COVID-19 vaccine to adults under 55 years of age,” and had requested a new risk analysis on the vaccine’s risks and benefits broken down by age and gender. On March 30, 2021, Germany limited its use to persons over the age of 60.
On April 7, 2021, the European Medicines Agency (EMA) safety committee (PRAC) concluded that “unusual blood clots with low blood platelets should be listed as very rare side effects of Vaxzevria (formerly COVID-19 Vaccine AstraZeneca).” In their report, PRAC reminded health care professionals and vaccine recipients to be aware of the possibility of “blood clots combined with low levels of blood platelets occurring within 2 weeks of vaccination.” PRAC reports that the blood clots occurred in the abdomen (splanchnic vein thrombosis), brain (cerebral venous sinus thrombosis or CVST), and arteries, in conjunction with low levels of blood platelets and at times with bleeding.
According to PRAC, “One plausible explanation for the combination of blood clots and low blood platelets is an immune response, leading to a condition similar to one seen sometimes in patients treated with heparin (heparin induced thrombocytopenia, HIT).” New studies and revised protocols to ongoing clinical trials have been requested by safety officials.
In a preprint study pending peer review released on April 20, 2021, German researchers describe what they believe to be the two-step mechanism responsible for the serious clotting reaction following the AstraZeneca COVID-19 vaccine. According to the scientists, the first step involves the activation of blood platelets when they come into contact with the adenovirus outer shell and the proteins from the cells where the vaccine grows. When this occurs in large numbers, a signal wakes up B-cells that then produces an enormous number of antibodies against the platelet factor 4 protein, which is what assists to coordinate blood clotting. The body then believes that it is responding to a huge number of pathogens in the body, and causes antibodies to bind to the platelets, pull in white blood cells, and cause a systemic disruption. The second step involves the calcium-binder and stabilizer, EDTA, that is an ingredient in the AstraZeneca vaccine. EDTA causes the blood vessel walls to open up and permit entry of the protein and platelet complexes to begin circulation in the blood stream which triggers the syndrome.
While many cases of the serious blood clotting disorder have occurred in women, lead author Dr. Andreas Greinacher reported that this disorder was not specific to one gender. Greinacher noted that since most health-care workers are women and part of the initial group of people to receive the vaccine, the tendency for cases to be reported among females was significantly higher.
An in-depth review of 24 cases of splanchnic vein thrombosis and 62 cases of cerebral venous sinus thrombosis reported to the EU drug safety database, EudraVigilance, as of March 22, 2021 was completed by the committee. Of these cases, 18 were reported as fatal. The committee, however, continues to recommend the vaccine, stating that “The reported combination of blood clots and low blood platelets is very rare, and the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.”
Vaccine use has resumed in many countries; however, some countries have restricted use of the product to persons over the age of 60 or 65 years of age. As of April 19, 2021, the vaccine remained suspended in Cameroon, Norway, and Denmark. On April 14, 2021, Danish health officials announced that it was halting use of the vaccine after studies had noted that blood clots occurred at a rate of one in 40,000 people.
As of April 22, 2021, more than 220 cases of blood clots in conjunction with low platelets had been reported by European regulators following AstraZeneca vaccination.
The AstraZeneca COVID-19 vaccine has also been linked to Guillain-Barré Syndrome (GBS). GBS, a serious neurological disorder where the body’s immune system attacks the peripheral nervous system, can cause muscle weakness, paralysis, and even death. On September 8, 2021, the EMA stated that GBS should be listed as a potential adverse event following vaccination. According to the EMA, as of July 31, 2021, 833 cases of GBS had been reported after AstraZeneca COVID-19 vaccination.
Inovio Pharmaceuticals INO-4800 DNA vaccine candidate
In early April 2020, Inovio pharmaceuticals began Phase 1 clinical trials of its experimental COVID-19 DNA vaccine, INO-4800. Inovio’s COVID-19 vaccine research has been funded by a $9 million grant from the Norway-based Coalition for Epidemic Preparedness Innovations (CEPI) and a $5 million grant from the Bill and Melinda Gates Foundation. It also has a partnership with Philadelphia’s Wistar Institute and Beijing Advaccine Biotechnology Co. in China to develop the vaccine in addition to a $11.9 million contract with the U.S. Department of Defense to provide the experimental DNA coronavirus vaccine for upcoming clinical trials and potential manufacturing of the vaccine for military personnel in the future.
Inovio’s INO-4800 vaccine injects a small piece of circular DNA, called a plasmid (pGX9501), that encodes for the entire length of the Spike glycoprotein of SARS-CoV-2 to provoke the vaccine recipient’s cells into producing antibodies. The biggest challenge for DNA/RNA vaccines is getting patients’ cells to accept the introduced genetic material. At this point, the most effective technique appears to be electroporation, which is the delivering short pulses of electrical current to the patient to open cell pores and allow the plasmids to enter. This vaccine, unlike many of its counterparts, is stable at room temperature for over a year.
On June 30, 2020, Inovio Pharmaceutical announced positive results from its Phase 1 clinical trials. Participants received either a 1.0mg or 2.0mg dose administered using INOVIO's CELLECTRA® 2000 device. According to company officials, all 10 reported adverse events were considered Grade 1 and involved localized injection site redness.
INOVIO’s CELLECTRA® 2000 electroporation device delivers short pulses of electrical current to the patient in addition to the vaccine. The electricity creates temporary pores in a patient’s cell membranes and this process enables the DNA/RNA to enter. The device is also associated with higher rates of injection site pain in comparison to standard injections.
In late September 2020, the U.S. Food and Drug Administration (FDA) placed the INO-4800 experimental vaccine trials on partial hold and requested more information on the clinical trials and the device used to deliver the vaccine. While the Phase 3 clinical trials remain on hold as of December 9, 2020, the FDA has permitted Inovio to proceed with Phase 2 clinical trials.
Inovio company officials report that they expect to provide regulators with the answers to any questions by the end of the second quarter of 2021. Vaccine trials, however, are progressing in China in partnership with Advaccine Biopharmaceuticals Suzhou Co Ltd.
In October 2020, it was reported that Inovio’s experimental COVID-19 vaccine neutralized SARS-CoV-2 viruses with the D614G mutation that had become globally dominate.
Inovio announced in November 2020 that their INNOVATE Phase 2/3 randomized, blinded, placebo-controlled safety and efficacy trial would be funded by the U.S. Department of Defense and by December of 2020 had published Phase 1 clinical trial data suggesting that the vaccine generated both humoral (neutralizing antibodies) and/or cellular responses in CD4 and CD8 T cells.
Maryland-based Novavax Inc, a biotechnology company which has never successfully delivered a product to market, has developed an experimental vaccine using recombinant nanoparticle technology. Referred to as a protein subunit vaccine, NVX‑CoV2373 contains Novavax’s patented saponin-based Matrix-M™ adjuvant designed to enhance the immune response and stimulate high levels of neutralizing antibodies.
Matrix-M1 contains nm (nanometers) of nanoparticles composed of Quillaja saponins, phospholipid and cholesterol. Quillaja saponins are chemical compounds extracted from the soapbox tree and are used as emulsifiers in food additives and beverages.
Phase 1/2 clinical trials involved 131 participants, with 83 administered the NVX-CoV2373 vaccine containing the Matrix-M1 adjuvant to help stimulate an immune response to produce a strong antibody response. Of the remaining trial participants, 25 were given the NVX-CoV2373 vaccine without the Matrix-M1 adjuvant and 23 participants were given a placebo of sterile 0.9 percent normal saline. Participant received two intramuscular injections in the deltoid muscle administered three weeks apart.
According to the results of the clinical trial, two of the 83 participants (one each in groups D and E) suffered “severe adverse events” (fatigue, headache, and malaise) after the first dose. Two participants—one each in groups A and E—had “reactogenicity events” (malaise, fatigue, and tenderness). Following administration of the second dose, one participant in group D had a “severe local event” (tenderness) and eight participants—one or two in each group—had “severe systemic events.” The most common of these severe systemic events were fatigue and joint pain. One participant in group D developed a fever greater than 100 °F.
Phase 3 clinical trials of NVX-CoV2373 began in the United Kingdom in late September 2020. This trial, a randomized, placebo-controlled, observer-blinded trial, was expected to enroll up to 10,000 volunteers. Half of the volunteers would be administered two intramuscular doses of the experimental vaccine candidate 21 days apart, while the remaining participants would receive a placebo.
On November 9, 2020, Novavax received “fast track” status from the U.S. Food and Drug Administration. This designation permitted the company to submit clinical data to the FDA when it became available rather than waiting for all results to be collected.
In late January 2021, company officials reported that the experimental vaccine was 89.3 percent effective at protecting individuals from illness. This data was based on interim results of late-stage clinical trials conducted in the U.K. The vaccine, however, was found to be only 49.4 percent effective in South African clinical trials, where the B.1.351(Beta) variant was most predominant.
By February 2021 Novavax had secured a memorandum of understanding with Canada and Takeda Pharmaceutical Company Ltd. (Japan) to produce the vaccine, while the European Medicines Agency (EMA) started their rolling reviews of the experimental vaccine. As Phase 3 trials continued in the United States and the United Kingdom, Novavax had secured advance commitments and purchase agreements totally over 1.2 billion doses of NVX-CoV2373 with GAVI, The Vaccine Alliance (formerly the Global Alliance for Vaccines and Immunization); Switzerland; Australia; New Zealand; and Canada.
On March 1, 2021, Novavax released pre-peer reviewed research results on their experimental NVX-CoV2373 vaccine. The Phase 2 component of their Phase 1/2 trial was a randomized placebo controlled trial to identify dosing regimen for the vaccine.
Vaccine arms of about 250 participants received one or two intramuscular doses at 5-μg or 25-μg or placebo, 21 days apart. Subsequent to randomization, 45 percent of participants were 50 to 84 years of age, and side effects were reported as mild and lasted about three days, with intensification after the second dose with the higher dosage of the vaccine.
The lower dose antibody response was reported as 100 percent for all age groups with neutralizing antibody rates exceeding those present in convalescent sera. The study concluded by stating that the two-dose regimen at the lower dose of 5-μg was suited for young and old alike and was highly protective.
In September 2021, Novavax company officials announced that it was initiating a Phase 1/2 study of a combination COVID-19-seasonal flu vaccine. The clinical trial will combine Novavax' recombinant protein-based NVX-CoV2373 COVID-19 vaccine and their NanoFlu™ vaccine candidates and patented saponin-based Matrix-M™ adjuvant in a single vaccine product.
Clinical trials will involve 640 healthy Australians between 50 and 70 years of age. Trial participants, however, must have previously been infected with SARS-CoV-2 or been vaccinated with an approved COVID-19 vaccine at least eight weeks prior to enrollment in the vaccine trial. Participants will be randomized to different cohorts to evaluate the safety and efficacy of different vaccine formulations and doses. Participants will receive two vaccine doses, spaced 56 days apart. Results from the clinical trial are expected to be available in the first part of 2022.
Convidicea. CanSino Biologics, Inc. of Tianjin, China, in partnership with China’s Academy of Military Medical Sciences’ Institute of Biotechnology, also began development of a COVID-19 vaccine, Convidicea (Ad5-nCoV), that employs a chimpanzee adenovirus vector using the HEK293 cell lines derived from tissue of an aborted fetus. Phase 1 clinical trials of the CanSino vaccine enrolled 108 participants, where 87 of whom (81 percent) experienced at least one adverse reaction within seven days of vaccination. The most common reactions included headache, pain, fever, and fatigue.
On May 12, 2020, the National Research Council of Canada (NRC) announced a collaborative agreement with the Chinese company to “advance bioprocessing and clinical development in Canada” of Convidicea vaccine. This agreement, however, was scrapped in late August due to shipping delays.
By December of 2020, Convidicea clinical trials had been launched in Saudi Arabia, Moscow, Mexico, and Chile, with advanced purchase agreements totaling 35 million doses.
Pakistan and Mexico approved Convidicea under emergency prior to approval by any international health organizations and completion of Phase 3 trials in early 2021.
CoronaVac. Beijing-based Sinovac Biotech Ltd began Phase 3 trials in July of CoronaVac, an inactivated coronavirus vaccine utilizing traditional vaccine manufacturing processes. To develop its vaccine, Sinovac obtained SARS-CoV-2 virus from patients globally, cultured and grew the virus in vero cells, which are derived from monkey kidneys. The virus was then inactivated with beta-propiolactone, a chemical derived from formaldehyde, and prepared and bottled as a vaccine.
In September 2020, reports indicated that health officials in China had already begun administering experimental COVID-19 vaccines under their emergency use laws to their citizens prior to completion of Phase 3 clinical trials. Frontline healthcare workers, public officials, border security personnel, persons considered high-risk for COVID-19 infection as well as pharmaceutical company officials and their families were first to be given the experimental vaccines. Persons receiving the vaccines were required to sign a “nondisclosure agreement” which would prevent them from sharing any details to the media.
On November 9, 2020, CoronaVac Phase 3 clinical trials were halted in Brazil due to a death that occurred in a vaccine trial recipient. Two days later, clinical trials resumed, and the death was reported as a suicide that was not related to vaccination.
As of December 16, 2020, CoronaVac was reported to be 50.65 percent effective against COVID-19 illness in Brazil among health care workers 18 years of age and older. Company officials reported the vaccine to be 91.25 percent effective in clinical trials conducted in Turkey; however, this data was based on a preliminary analysis of only 29 cases. The Indonesia trial reported a vaccine effectiveness of 65.3 percent. China approved the vaccine for use by the general public in early February 2021. As March 2021 began, CoronaVac is in use or scheduled for use in Tunisia, the Philippines, Mexico, Malaysia, Turkey, Indonesia. Brazil followed suit in March 2021, though a week earlier it was reported that a small study awaiting peer-review found that CoronaVac may not be as effective against the new COVID-19 Amazonian variant that is reported as aggressively spreading in Brazil.
In June 2021, China authorized CoronaVac vaccine for children between the age of 3 and 17 years. By July 2021, company officials announced that a non-peer reviewed study found that the use of a third vaccine dose invoked a strong immune response and that adverse events were lower than those seen following the initial 2-dose series.
A study published in the Lancet reported an increased risk of Bell’s Palsy following CoronaVac vaccine but that the benefits of vaccination outweighed the risk.
A COVID-19 vaccine using viral vector technology, Sputnik V, developed in partnership between the Russian research institution, the Gamaleya National Center of Epidemiology and Microbiology, and the Russian Direct Investment Fund, received approval for widespread use by Russian authorities in early August 2020. Sputnik V uses two different strains of adenovirus and requires a second vaccine dose after 21 days to boost the immune response. The Lancet published data on the vaccine’s Phase 1/2 trials on September 4, 2020. Concerns about the lack of transparency related to pre-licensing clinical trial results had been expressed by some in the scientific community.
On February 2, 2021, interim results from the Sputnik V (Gam-COVID-Vac) Phase 3 trials were published in The Lancet, which reported the vaccine to be 91.6 percent effective at 21 days following administration of the first vaccine dose (on the day that dose 2 was administered). Clinical trials of this vaccine included healthy adults 18 years of age and older who were negative for SARS-CoV-2 at baseline. Seventy serious adverse events were reported among 68 trial participants across both the vaccine group and the control group; however, trial investigators declared that none were related to vaccination. Four deaths occurred during the Phase 3 trials, three in vaccine recipients and one in the placebo group. No deaths were considered to be related to vaccination. Researchers report that the durability of vaccine acquired immunity is not known and it is not known whether the vaccine can halt transmission of SARS-CoV-2.
In early February 2021, Russian vaccine developers reported that they were in discussions with China’s CanSino Biologics to study whether the second dose of the Sputnik V vaccine could be replaced with the COVID-19 vaccine manufactured by the Chinese vaccine maker. Vaccine researchers are looking to find out if combining COVID-19 vaccines made by different pharmaceutical companies could still offer adequate vaccine acquired immunity, or even better protection against the emerging virus variants.
By March 2021, Sputnik V vaccine distribution agreements spanned more than 50 countries. On June 17, 2021, company officials reported that a booster dose targeting the Delta variant would soon be available.
Since the fall of 2020, multiple variants of the SARS-CoV-2 virus have emerged. U.S. public health officials report that while the current COVID-19 vaccines approved under EUA appear to be effective against the variants, they are in the process of developing guidance to help vaccine manufacturers adapt their products as needed. FDA officials report that:
“For authorized vaccines, our teams are currently deliberating and discussing the types of data needed to support changes in the composition of the vaccine, either through altering the existing vaccine or through the addition of new vaccine component(s), including how sponsors could demonstrate immune response to new variants through streamlined clinical programs that still gather the crucial data the FDA needs to demonstrate effectiveness, but can be executed quickly to gather this data.”
Pfizer-BioNTech reports its COVID-19 vaccine to be just as effective against the U.K.’s B.1.1.7 (Alpha) as the earlier variant of SARS-CoV-2 virus. The vaccine, however, appears to be less effective against the South African B.1.351 (Beta) variant. In April 2021, researchers from Tel Aviv University reported findings of a small study on the effectiveness of the Pfizer-BioNTech vaccine against the B.1.351 (Beta) variant. The study, which was released prior to peer review, found that vaccinated people were eight times more likely to become infected with this SARS-CoV-2 variant than unvaccinated individuals.
On February 25, 2021, Pfizer-BioNTech announced that they had begun evaluating the safety and effectiveness of a third dose of their COVID-19 vaccine. The study was designed to learn more about the effects of a booster dose on currently circulating and newly emerging SARS-CoV-2 variants. Specifically, Phase 1 clinical trial participants would be offered a 30µg booster dose of the current vaccine 6 to 12 months after completing the two-dose vaccine series.
Additionally, company officials reported that they were in discussions with the FDA and the European Medicines Agency regarding plans for a clinical study of variant specific vaccines, including a vaccine targeting the South African B.1.351 (Beta) variant.
Moderna reports that its COVID-19 vaccine appears to offer vaccine-acquired protection against the U.K’s B.1.1.7 (Alpha) variant. The vaccine, however, had a six-fold reduction against the South African B.1.351 (Beta) variant when compared to the initial SARS-CoV-2 virus.
On February 24, 2021, company officials announced that it had completed manufacturing of materials for a variant-specific vaccine targeting the South African B.1.351 (Beta) variant. Additionally, Moderna stated that they were planning to move forward with two unique study strategies.
First, Moderna reported planned to evaluate three approaches to boosters. These included: clinical trials of a booster dose of a vaccine targeting the South African B.1.351(Beta) variant; clinical trials of a multi-variant vaccine dose targeting the original SARS-CoV-2 virus and the South African B.1.351(Beta) variant; and clinical trials of a 50µg booster dose of the current vaccine. Second, company officials reported plans to begin studies on the use of the vaccine candidate targeting the South African B.1.351(Beta) variant dose and the experimental multi-variant vaccine dose as a primary vaccination series in persons who are seronegative for SARS-CoV-2.
Health officials in South Africa have halted use of the AstraZeneca COVID-19 vaccine after the vaccine was found to be less than 25 percent effective against the B.1.351 (Beta) variant, which is most common SARS-CoV-2 virus variant circulating in South Africa.
On May 4, 2021, the CDC classified the SARS-CoV-2 variant B.1.617 (Delta) and it’s three sub lineages, B.1.617.1, B.1.617.2, and B.1.617.3, as variants of interest. These variants, which originated in India, were declared variants of concern by the World Health Organization (WHO) on May 10, 2021. According to the WHO, these variants were associated with increased transmissibility and decreased neutralization. As a result, vaccinated individuals and persons who have previously recovered from a COVID-19 infection may be at risk for infection from this variant.
A technical briefing published by Public Health England on June 11, 2021 noted that almost one third of individuals who died from the COVID-19 Delta variant were fully vaccinated. In the June 18, 2021 Public Health England Technical report, the death rate in fully vaccinated individuals was 6.6 times higher than among unvaccinated people.
By the end of June 2021, almost 90 percent of COVID-19 cases in Israel were reported as being from the Delta variant, with 50 percent occurring in fully vaccinated adults. By late June 2021, Israeli officials report a 30 percent decrease in the vaccine’s ability to prevent infection and mild to moderate illness from COVID-19 disease caused by the Delta variant. The vaccine’s effective against the Delta variant continued to drop and by the end of July 2021, the vaccine was reported to be only 39 percent effective in Israel.
On July 27, 2021, the CDC issued a Health Alert Network health advisory regarding the increasing rates of COVID-19 infections related to the Delta variant. In this alert, the CDC noted that the Delta variant accounted for approximately 80 percent of all COVID-19 cases in the U.S. and that fully vaccinated individuals could still become infected and transmit the virus to others.
Pfizer company officials reported that they would be seeking approval for a third booster dose to target the Delta variant by August 2021.
On July 8, 2021, the CDC and FDA issued a joint press release stating that COVID-19 vaccine booster doses were not required at this time. They did, however, state that federal health officials were monitoring data and they would continue to inform the public. However, one month later, in August 2021, the FDA approved use of a third dose of mRNA vaccine in persons with certain immunosuppressive conditions such as solid organ transplant recipients. The CDC’s ACIP recommended use of the third vaccine dose on August 13, 2021.
One week later, on August 18, 2021, the U.S. Department of Health and Human Services (HHS) released a public statement on a plan for COVID-19 vaccine booster doses beginning September 20, 2021. Public health officials reported that booster doses should be given eight months following the receipt of the second dose of mRNA vaccine. Booster doses of the Johnson & Johnson/Janssen COVID-19 vaccine were also anticipated; however, health officials reported a lack of available data to advise the use of an additional dose. CDC Director Dr. Rochelle Walensky also reported that annual COVID-19 vaccine doses were not anticipated because health officials believe that a third dose will provide sufficient long-term protection.
Prior to the September 17, 2021 FDA Vaccine and Related Biological Products Advisory Committee (VRBPAC) meeting, Pfizer released data showing that the COVID-19 vaccine waned by 6 percent each month and reported that within 6 to 8 months, the vaccine offered limited protection. Company officials also acknowledged that the failure of the vaccine to protect individuals was related to waning vaccine effectiveness and not because of escaping protection from the Delta variant.
On September 17, 2021, VRBPAC voted to authorize use of a third booster dose of the Pfizer-BioNTech mRNA COVID-19 vaccine under EUA in persons 65 years of age and older as well as those who are at high risk of severe illness. The booster dose for this population is recommended at 6 months following administration of the second dose.
The FDA amended the Pfizer-BioNTech EUA on September 22, 2021 and authorized a booster dose in all persons 65 years and older, in individuals 50 through 64 years at high risk for COVID-19, and in persons 18 through 64 “whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of COVID-19 including severe COVID-19.”
While the CDC’s ACIP voted on September 23, 2021 to recommend booster doses in all persons 65 and older, in persons 50 through 64 years with pre-existing health conditions that put them at increased risk from COVID-19 infection, and in persons 18 through 49 who are at risk of infection due to pre-existing health conditions if the individual believes that they need one, they voted against recommending a booster dose for all persons 18 through 64 years whose living or employment situation places them at high risk for COVID-19 infection. CDC Director Dr. Rochelle Walensky, however, overruled ACIP and went ahead and issued a recommendation for a booster dose of Pfizer-BioNTech COVID-19 vaccine in all persons 18 and older who work or live in high-risk settings.
According to a pre-peer review study conducted by researchers from the Mayo Clinic and nference, a data analytics company, by July 2021, the Pfizer-BioNTech COVID-19 vaccine was reported to be only 42 percent, while the Moderna was reported to be 76 percent effective. This study was conducted during a time when approximately 70 percent of the case were reported as being of the Delta variant. A CDC study published in mid-August 2021 reported that among nursing care facility residents, mRNA vaccines were only 53.1 percent effective against the Delta variant.
On October 2, 2020, the National Academies of Sciences, Engineering, and Medicine released its final report which recommended a four-phase plan for the equitable allotment of a COVID-19 vaccine. According to the plan outlined by the Academies, during the time when vaccine supply is limited, the following phases of vaccine administration should be followed “to maximize societal benefit by reducing morbidity and mortality caused by the transmission of SARS-CoV-2.”
- Phase 1a – Front-line health care workers who are at risk of exposure to SARS- CoV-2 and of transmitting the virus to others.
- Phase 1b – Persons of all ages with underlying health conditions and comorbidities which places them at a high risk of severe illness or death from COVID-19. This also includes persons 65 years of age and older who are living in group settings which include nursing homes, jails, shelters, etc.
- Phase 2 – Essential workers, including childcare workers, school staff, and K-12 teachers. Persons considered at moderate risk of severe illness are also included in this group. Phase 2 also includes any persons 65 and older not included in Phase 1.
- Phase 3 – Children and young adults, as well as persons who work in areas considered to be at a moderate high risk of exposure but at low risk for severe illness.
- Phase 4 – Any remaining individuals.
Notably, the above recommended allocation plan would distribute COVID-19 vaccines to individuals with underlying health conditions and morbidities that had been identified by the National Academies of Sciences, Engineering, and Medicine as placing them at higher risk for severe complications from COVID-19, despite the fact that these vaccines were not tested on these at-risk populations. In real-world terms, because experimental COVID-19 vaccine clinical trials were conducted with healthy individuals, the potential for vaccine adverse events in at-risk populations are unknown.
On December 1, 2020, the CDC’s Advisory Committee on Immunization Practices (ACIP), which makes non-binding use recommendations that may be adopted by the CDC, recommended that both health care providers and residents of long-term care facilities be offered COVID-19 vaccination in the initial phase (Phase 1a) of vaccine distribution.
ACIP updated its COVID-19 vaccine allocation recommendations on December 20, 2020, and stated that in the second phase of the vaccine allocation (Phase 1b), persons 75 years of age and older and non-healthcare frontline workers should receive the vaccine. The third phase of vaccine allocation (Phase 1c) recommendations included persons aged 65 to 74, persons between 16 and 64 years with high-risk medical conditions, and essential workers who were not included in the Phase 1b rollout.
As of May 12, 2021, all persons 12 years of age and older were considered eligible for the COVID-19 vaccine and the CDC reports that vaccines are widely availability in the U.S.
A third dose of mRNA vaccine has also been authorized for use by the FDA and recommended by ACIP for use in persons with certain immunosuppressive conditions such as solid organ transplant recipients and in persons with similar immunocompromising conditions.
IMPORTANT NOTE: NVIC encourages you to become fully informed about covid-19 and the covid-19 vaccine by reading all sections in the Table of Contents, which contain many links and resources such as the manufacturer product information inserts, and to speak with one or more trusted health care professionals before making a vaccination decision for yourself or your child. This information is for educational purposes only and is not intended as medical advice.
Updated October 20, 2021
1 Gates Foundation. Bill & Melinda Gates Foundation Dedicates Additional Funding to the Novel Coronavirus Response. Gates Foundation Feb. 5, 2020.
2 World Health Organization. World experts and funders set priorities for COVID-19 research. Feb. 12, 2020.
3 Moran N. WHO releases COVID-19 roadmap funding efforts in progress. BioWorld Mar. 9, 2020.
7 National Institutes of Health. NIH clinical trial of investigational vaccine for COVID-19 begins. Mar. 16, 2020.
9 Inovio Pharmaceuticals. Ology Bioservices, Inovio Partner to Manufacture COVID-19 DNA Vaccine with $11.9 Million Department of Defense Grant. Inovio Bioservices, Inc. Mar. 24, 2020.
12 Mundy A. How Big Pharma is Getting Ready to Blackmail Americans. DC Report Apr. 5, 2020.
13 HHS Assistant Secretary for Preparedness and Response. HHS Accelerates Clinical Trials, Prepares for Manufacturing of COVID-19 Vaccines. Mar. 30, 2020.
14 HHS Assistant Secretary for Preparedness and Response. Pandemic and All Hazards Preparedness Act Progress Report. November 2007.
15 U.S. Department of Health & Human Services. ASPR 2020 Budget in Brief ($2.6B): Biomedical Advanced Research and Development Authority ($1.6B) – $256M for pandemic influenza. Feb. 13, 2020.
16 Fisher BL. Letter to Col. Robert Kadlec, MD (USAF, ret.), Staff Director, US Senate Subcomittee on Bioterrorism and Public Health Preparedness. Nov. 15, 2005. Also CNBC. Pandemic Flu Vaccine and Liability Protection Debate on “Closing Bell” with Barbara Loe Fisher and Christopher Paul Milne, PhD. Dec. 22, 2005.
17 Johnson & Johnson. Johnson & Johnson Announces a Lead Vaccine Candidate for COVID-19; Landmark New Partnership with U.S. Department of Health and Human Services; and Commitment to Supply One Billion Vaccines Worldwide for Emergency Pandemic Use. Mar. 20, 2020.
18 Steenhuysen J. J&J, Moderna sign deals with U.S. to produce huge quantity of possible coronavirus vaccines. Reuters Mar. 30, 2020.
19 U.S. Department of Health & Human Services. Trump Administration Announces Framework and Leadership for 'Operation Warp Speed'. May 15, 2020.
20 Weise E. FDA says a coronavirus vaccine would have to be at least 50% effective to be approved. USA Today July 1, 2020.
21 U.S. Food and Drug Administration. Emergency Use Authorization for Vaccines to Prevent COVID-19 - Guidance for Industry. July 26, 2021.
23 Walker M. FDA Panel Stresses Safety, Diversity, Efficacy for COVID-19 Vax. MedPage Today Oct. 23, 2020.
24 Walker M. FDA Panel Stresses Safety, Diversity, Efficacy for COVID-19 Vax. MedPage Today Oct. 23, 2020.
25 Cohen J. ‘There’s only one chance to do this right’—FDA panel wrestles with COVID-19 vaccine issues. American Association for the Advancement of Science Oct. 23, 2020.
26 Walker M. FDA Panel Stresses Safety, Diversity, Efficacy for COVID-19 Vax. MedPage Today Oct. 23, 2020.
27 Walker M. FDA Panel Stresses Safety, Diversity, Efficacy for COVID-19 Vax. MedPage Today Oct. 23, 2020.
28 Cohen J. ‘There’s only one chance to do this right’—FDA panel wrestles with COVID-19 vaccine issues. American Association for the Advancement of Science Oct. 23, 2020.
29 Walker M. FDA Panel Stresses Safety, Diversity, Efficacy for COVID-19 Vax. MedPage Today Oct. 23, 2020.
30 Walker M. FDA Panel Stresses Safety, Diversity, Efficacy for COVID-19 Vax. MedPage Today Oct. 23, 2020.
31 Walker M. FDA Panel Stresses Safety, Diversity, Efficacy for COVID-19 Vax. MedPage Today Oct. 23, 2020.
32 Walker M. FDA Panel Stresses Safety, Diversity, Efficacy for COVID-19 Vax. MedPage Today Oct. 23, 2020.
33 Shah A, Marks P, Hahn S. Ensuring the safety and effectiveness of a covid-19 vaccine. HealthAffairs Aug. 18, 2020.
34 U.S. Food and Drug Administration. August 23, 2021 Summary Basis for Regulatory Action – Comirnaty. Aug. 23, 2021.
36 Rauch S., Jasny E. et al. New Vaccine Technologies to Combat Outbreak Situations. Front Immunol 2018; 9:1963.
37 Fisher BL Raines K. Inovio COVID-19 Vaccine Uses Electricity to Drive DNA Into Body Cells. The Vaccine Reaction Apr. 18, 2020.
38 Cross R. Will the coronavirus help mRNA and DNA vaccines prove their worth? Chemical and Engineering News Apr. 3, 2020.
39 Cross R. Will the coronavirus help mRNA and DNA vaccines prove their worth? Chemical and Engineering News Apr. 3, 2020.
43 National Institutes of Health - National Institute of Allergy and Infectious Diseases (NIAID). NIH Clinical Trial of Investigational Vaccine for COVID-19 Begins Study Enrolling Seattle-Based Healthy Adult Volunteers. Mar. 16, 2020.
44 ABNewswire. Scientists Test Potential Coronavirus Vaccine Straight on Humans Skipping Mice Trials. Benzinga Mar. 31, 2020.
45 Moderna, Inc. Moderna’s Work on a Potential Vaccine Against COVID-19. Mar. 30, 2020.
46 Cross R. Will the coronavirus help mRNA and DNA vaccines prove their worth? Chemical and Engineering News Apr. 3, 2020.
47 Moderna Inc. Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. May 18, 2020.
48 U.S. Department of Health & Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Nov. 27, 2017.
49 National Institutes of Health - National Institute of Allergy and Infectious Diseases (NIAID). Phase 3 clinical trial of investigational vaccine for COVID-19 begins. July 27, 2020.
50 National Institutes of Health - National Institute of Allergy and Infectious Diseases (NIAID). Phase 3 clinical trial of investigational vaccine for COVID-19 begins. July 27, 2020.
51 CBS2’s Dr. Max Gomez Explains Why Moderna’s COVID Vaccine Trial Has Been Slowed. CBS2 New York Oct. 7, 2020.
52 Guzman J. Moderna completes enrollment for its COVID-19 vaccine trial. The Hill Oct. 22, 2020.
53 Moderna. Slide 4: © 2020 ModernaSlide4Risk factors for severe COVID-19 disease. In: Moderna Cove Study. Oct. 21, 2020.
54 Dall C. Early data show Moderna's COVID vaccine 94.5% effective. CIDRAP News Nov. 16, 2020.
55 U.S. Food and Drug Administration. FDA Takes Additional Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for Second COVID-19 Vaccine. Dec. 18, 2020.
56 U.S. Centers for Disease Control and Prevention. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Moderna COVID-19 Vaccine — United States, December 21, 2020–January 10, 2021. MMWR Jan. 29, 2021; 70(4):125–129.
57 Cáceres M. Hammerin’ Hank’s COVID-19 Vaccination: A “Double-Edged Sword”? The Vaccine Reaction Jan. 31, 2021.
58 Ellis R. Pfizer, Moderna Say Booster Shots Probably Needed. WebMD Brief April 16, 2021.
60 U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals. Aug. 12, 2021.
61 U.S. Centers for Disease Control and Prevention. Joint Statement from HHS Public Health and Medical Experts on COVID-19 Booster Shots. In: CDC Newsroom. Aug. 18, 2021.
62 Pettypiece S, Strickler L. Moderna expected to miss Sept. 20 deadline for booster approval. NBC News Sept. 3, 2021.
63 Holzberg M. Moderna Says Covid-19 Vaccine Is 96% Effective In Teenagers, Will File For Full FDA Approval. Forbes May 6, 2021.
65 Swift R. O’donnell C. Moderna to recall COVID-19 doses in Japan after stainless steel contaminants found. Reuters Sept. 1, 2021.
66 Hackett DW. Japan Drops Moderna For Un-Authorized COVID-19 Vaccine. Precision Vaccinations Sept. 9, 2021.
67 Hackett DW. Japan Drops Moderna For Un-Authorized COVID-19 Vaccine. Precision Vaccinations Sept. 9, 2021.
68 Williams S. COVID-19 Vaccines: How Much Revenue Will Each Drugmaker Generate in 2021? The Motley Fool July 13, 2021.
69 TVR Staff. Pfizer and BioNTech Begin Human Clinical Trials of COVID-19 Vaccine in U.S. The Vaccine Reaction May 25, 2020.
70 TVR Staff. Pfizer and BioNTech Begin Human Clinical Trials of COVID-19 Vaccine in U.S. The Vaccine Reaction May 25, 2020.
71 TVR Staff. Pfizer/BioNTech’s COVID-19 Vaccine Causes Adverse Reactions in Over Half of Clinical Trial Volunteers. The Vaccine Reaction July 18, 2020.
72 BusinessWire. Pfizer and BioNTech Choose Lead mRNA Vaccine Candidate Against COVID-19 and Commence Pivotal Phase 2/3 Global Study. July 27, 2020.
73 BusinessWire. Pfizer and BioNTech Propose Expansion of Pivotal COVID-19 Vaccine Trial. Press Release Sept. 12, 2020.
74 Reuters. Coronavirus vaccine study by Pfizer shows mild-to-moderate side effects. Fox Business Sept. 15, 2020.
76 Chander V. Pfizer files COVID-19 vaccine application to U.S. FDA. Reuters Nov. 20, 2020.
77 U.S. Food and Drug Administration FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine. Dec. 11, 2020.
78 Reynolds E, Halasz S, Pleitgen F, Isaac L. UK becomes first country to authorize Pfizer/BioNTech's Covid-19 vaccine, first shots roll out next week. CNN Dec. 3, 2020.
79 Smout A UK issues anaphylaxis warning on Pfizer vaccine after adverse reactions. Reuters Dec. 9, 2020.
80 TVR Staff Patient in Georgia, Health Worker in New York Suffer Anaphylaxis After Getting Pfizer/BioNTech COVID-19 Vaccine. The Vaccine Reaction Dec. 28, 2020.
81 U.S. Centers for Disease Control and Prevention. Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine — United States, December 14–23, 2020. MMWR Jan. 15, 2021; 70(2):46–51
82 Fisher BL. Miami Obstetrician Develops Bleeding Disorder, Dies After Getting COVID-19 Vaccine. The Vaccine Reaction Jan. 11, 2021.
83 Torjesen I. Covid-19: Norway investigates 23 deaths in frail elderly patients after vaccination. BMJ 2021, Jan.15; 372.
84 TVR Staff. Two Elderly Men Die Hours After Getting COVID-19 Vaccines in Israel. The Vaccine Reaction Jan. 1, 2021.
85 Torjesen I. Covid-19: Norway investigates 23 deaths in frail elderly patients after vaccination. BMJ 2021, Jan.15; 372.
86 TVR Staff. Four Persons Die Days After COVID-19 Vaccinations in Portugal, Switzerland and Norway. The Vaccine Reaction Jan. 11, 2021.
87 Schmidt AW. Pfizer vaccine vials hold extra doses, could expand US supply. New York Post Dec. 16, 2020.
88 Elizalde E. Pfizer to ship fewer vials of COVID vaccine to US after extra doses discovered. New York Post Jan. 22, 2021.
89 Rowland C. Biden wants to squeeze an extra shot of vaccine out of every Pfizer vial. It won’t be easy. The Washington Post Jan. 22, 2021.
90 U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Adolescents in Another Important Action in Fight Against Pandemic. May 10, 2021.
91 Soucheray S. CDC advisers green-light COVID vaccine in young teens. CIDRAP News May 12, 2021.
92 U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Pfizer-BioNTech COVID-19 Vaccine for Emergency Use in Adolescents in Another Important Action in Fight Against Pandemic. May 10, 2021.
93 U.S. Food and Drug Administration. Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers): Emergency Use Authorization (EUA) of the Pfizer-BioNTech COVID-19 Vaccine to Prevent Coronavirus Disease 2019 (COVID-19). June 25, 2021.
94 Wallace M. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Pfizer-BioNTech COVID-19 Vaccine. Centers for Disease Control May 12, 2021.
96 Lonas L. FDA aims to give full approval to Pfizer vaccine by Labor Day: report. The Hill Aug. 4, 2021.
100 Hendler C, Wrangham T, Cáceres M. FDA Approves BioNTech’s Comirnaty. Pfizer COVID Shot Remains Experimental. The Vaccine Reaction Sept. 4, 2021.
101 Hendler C, Wrangham T, Cáceres M. FDA Approves BioNTech’s Comirnaty. Pfizer COVID Shot Remains Experimental. The Vaccine Reaction Sept. 4, 2021.
102 Fisher BL, Pebsworth V, Wrangham T, et al. NVIC letter – FDA RADM Hinton for Clarifications on FDA August 23, 2021 EUA Reissue Letter to Pfizer. National Vaccine Information Center Aug. 30, 2021.
104 Jenco M. CDC panel OKs COVID-19 vaccines; discusses myocarditis, boosters. AAP News Aug. 30, 2021.
106 Lardieri A. Pfizer Applies for Full FDA Approval of Coronavirus Vaccine. U.S. News and World Report May 7, 2021.
107 Iacobucci G. Covid-19: FDA set to grant full approval to Pfizer vaccine without public discussion of data. BMJ 2021; 374
108 Shah A, Marks P, Hahn S. Ensuring the safety and effectiveness of a covid-19 vaccine. HealthAffairs Aug. 18, 2020.
109 Wastila L, Doshi P, Merchant M, Witczak K. Why we petitioned the FDA to refrain from fully approving any covid-19 vaccine this year. BMJ Opinion. 8 June 2021.
110 Iacobucci G. Covid-19: FDA set to grant full approval to Pfizer vaccine without public discussion of data. BMJ 2021; 374
111 U.S. Food and Drug Administration. August 23, 2021 Summary Basis for Regulatory Action – Comirnaty. Aug. 23, 2021.
112 U.S. Food and Drug Administration. Comirnaty and Pfizer-BioNTech COVID-19 Vaccine – Fact Sheet for Healthcare Providers Administering Vaccine. Aug. 23, 2021.
113 Goodman B. CDC Panel Unanimously Backs Pfizer Vaccine After FDA Approval. WebMD Aug. 31, 2021.
114 Ellis R. Pfizer, Moderna Say Booster Shots Probably Needed. WebMD News Brief Apr. 16, 2021.
116 U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals. Aug. 12, 2021.
117 U.S. Centers for Disease Control and Prevention. Joint Statement from HHS Public Health and Medical Experts on COVID-19 Booster Shots. In: CDC Newsroom. Aug. 18, 2021.
118 Mandavilli A. In a new review, some F.D.A. scientists and others say boosters aren’t needed for the general population. The New York Times Sept. 13, 2021.
119 Krause PR, Fleming TR, Peto R, et al. Considerations in boosting COVID-19 vaccine immune responses. Lancet Sept. 13, 2020.
120 Schnirring L. FDA advisors OK Pfizer COVID booster for seniors, high-risk groups. CIDRAP News Sept. 17, 2021.
121 U.S. Food and Drug Administration. FDA Authorizes Booster Dose of Pfizer-BioNTech COVID-19 Vaccine for Certain Populations. Sept. 22, 2021.
122 Goodman B. CDC Chief Overrules Panel, OKs Boosters for Healthcare Workers. Medscape Sept. 23, 2021.
123 Lovelace Jr. B. Pfizer expects about $15 billion in 2021 sales from Covid vaccine. CNBC Feb. 2, 2021.
124 Parpia R. Pfizer Raises Sales Forecast for COVID-19 Biologic to $33.5 Billion in 2021. The Vaccine Reaction Aug. 16, 2021.
125 Dunleavy K. Floating material found in Pfizer COVID-19 vaccine vials in Japan, but company says it's not contamination. Fierce Pharma Sept. 15, 2021.
126 TVR Staff. Israel Studying Possible Link Between Heart Inflammation and Pfizer/BioNTech COVID-19 Shot. The Vaccine Reaction May 17, 2021.
127 U.S. Centers for Disease Control and Prevention. COVID-19 VaST Work Group Technical Report – May 17, 2021. In: Advisory Committee on Immunization Practices (ACIP). May 20, 2021.
128 Fonrouge G. ‘We clearly have an imbalance’: CDC holding emergency meeting over COVID vax concern. New York Post June 11, 2021.
129 Woolfolk J. CDC delays meeting on kids’ COVID vaccine heart risk - New federal Juneteenth holiday prompts rescheduling. The Mercury News June 18, 2021.
132 Wallace M, Oliver S. COVID-19 mRNA vaccines in adolescents and young adults: Benefit-risk discussion. U.S. Centers for Disease Control and Prevention June 23, 2021.
133 Soucheray S. Experts: mRNA COVID-19 vaccines likely tied to heart inflammation. CIDRAP News June 23, 2021.
134 Montgomery J, Ryan M, Engler R. et al. Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military. JAMA Cardiol. Jun 29, 2021; Epub ahead of print. PMID: 34185045.
135 Kim HW, Jenista ER, Wendell DC. et al. Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination. JAMA Cardiol. 2021 Jun 29, 2021; Epub ahead of print. PMID: 34185046.
136 Barda N, Dagan N, Ben-Shlomo Y. et al. Safety of the BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Setting. N Engl J Med. Aug 25, Epub ahead of print. PMID: 34432976.
137 Hoeg TB, Krug A, Stevenson J. et al. SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis. medRxiv Sept. 8, 2021.
138 Hoeg TB, Krug A, Stevenson J. et al. SARS-CoV-2 mRNA Vaccination-Associated Myocarditis in Children Ages 12-17: A Stratified National Database Analysis. medRxiv Sept. 8, 2021.
139 U.S. Centers for Disease Control and Prevention. Selected Adverse Events Reported after COVID-19 Vaccination. In COVID-19. Oct. 13, 2021.
140 U.S. Food and Drug Administration. FDA Statement on Following the Authorized Dosing Schedules for COVID-19 Vaccines. Jan. 4, 2021.
141 Drillinger M. U.K. OKs Delaying COVID-19 Vaccine Booster Despite Lack of Evidence. Healthline Jan. 12, 2021.
142 University of Oxford. Com-COV – Comparing COVID-19 Vaccine Schedule Combinations. No Date. Accessed Oct. 16, 2021.
144 Shaw RH, Stuart A, Greenland M. et al. Heterologous prime-boost COVID-19 vaccination: initial reactogenicity data. Lancet. May 2021:S0140-6736(21)01115-6.
145 Johnson & Johnson. Johnson & Johnson Announces a Lead Vaccine Candidate for COVID-19; Landmark New Partnership with U.S. Department of Health and Human Services; and Commitment to Supply One Billion Vaccines Worldwide for Emergency Pandemic Use. Mar. 20, 2020.
146 Levine H. The 5 Stages of COVID-19 Vaccine Development: What You Need to Know About How a Clinical Trial Works. Johnson & Johnson Sept. 23, 2020.
147 Weintraub A. J&J COVID-19 vaccine candidate protects monkeys after single dose. Fierce Biotech July 30, 2020.
149 Mahaney B. Johnson & Johnson Kicks Off Phase 2 Covid-19 Vaccine Trial In Spain – Report. Yahoo Finance Sept. 14, 2020.
150 Wamsley L., Harris R., Romo V. Johnson & Johnson, Eli Lilly Pause COVID-19 Drug Trials. National Public Radio Oct. 13, 2020.
151 Herper M. Covid-19 vaccine trials from AstraZeneca, Johnson & Johnson to restart. Stat News Oct. 23, 2020.
152 Steenhuysen J., O’Donnell C., Chander V. AstraZeneca resumes U.S. COVID-19 vaccine trial and next week J&J prepares to do same. Reuters Oct. 23, 2020.
153 Soucheray S. J&J vaccine shown to prevent 85% of severe COVID-19 disease. CIDRAP News Jan. 29, 2021.
154 U.S. Food and Drug Administration. FDA Issues Emergency Use Authorization for Third COVID-19 Vaccine. Feb. 27, 2021.
155 U.S Food and Drug Administration. Janssen COVID-19 Vaccine - Fact Sheet for Healthcare Providers Administering Vaccine. Aug. 27, 2021.
156 U.S Food and Drug Administration. Janssen COVID-19 Vaccine - Fact Sheet for Healthcare Providers Administering Vaccine. Aug. 27, 2021.
157 Soucheray S. US halts J&J COVID vaccine after reports of blood clots. CIDRAP News Apr. 13, 2021.
158 Soucheray S. ACIP opts to lift pause on Johnson & Johnson vaccine. CIDRAP News Apr. 23, 2021.
159 Lee M. Pause on Johnson & Johnson COVID-19 Vaccine Lifted: CDC Vaccine Advisory Committee. The Epoch Times. Apr. 23, 2021.
160 U.S. Food and Drug Administration. Janssen COVID-19 Vaccine - Fact Sheet for Healthcare Providers Administering Vaccine. Aug. 27, 2021.
161 Shimabukuro T. Update: Thrombosis with thrombocytopenia syndrome (TTS) following COVID-19 vaccination. U.S. Centers for Disease Control and Prevention May 12, 2021.
162 U.S. Centers for Disease Control and Prevention. Selected Adverse Events Reported after COVID-19 Vaccination. In: COVID-19. Oct. 13, 2021.
163 George J. FDA To Warn About Post-COVID Vax Guillain-Barré Syndrome — Cases seen in people who received Johnson & Johnson's vaccine. MedPage Today July 12, 2021.
164 U.S. Centers for Disease Control and Prevention. Selected Adverse Events Reported after COVID-19 Vaccination. In: COVID-19. Oct. 13, 2021.
165 European Medicines Agency. Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 30 August – 2 September 2021. Sept. 3, 2021.
166 Phillips J. Reports of Rare Body Inflammation After COVID-19 Vaccinations Being Investigated by EU Watchdog. The Epoch Times Sept. 3, 2021.
167 U.S. Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee February 26, 2021 Meeting Briefing Document- FDA. Feb. 26, 2021.
168 U.S. Food and Drug Administration. FDA Issues Emergency Use Authorization for Third COVID-19 Vaccine. Feb. 27, 2021.
169 LaFraniere S, Weiland N. Johnson & Johnson’s vaccine is delayed by a U.S. factory mixup. The New York Times Mar. 31, 2021.
170 Swaine J, Rowland C. Emergent plant that ruined Johnson & Johnson vaccine doses had prior FDA violations. The Washington Post Apr. 1, 2021.
171 Kansteiner F. FDA blasts troubled COVID-19 vaccine producer Emergent for quality control and cleanliness issues. Fierce Pharma Apr. 21, 2021.
172 Lovelace Jr. B. Johnson & Johnson reports $100 million in quarterly sales from Covid vaccine. CNBC Apr. 20, 2021.
173 Lovelace Jr. B. J&J CEO says people may need annual Covid vaccine shots for the next several years. CNBC Feb. 9, 2021.
175 Soucheray S. CDC, FDA recommend 3rd COVID vaccine dose for immune-compromised. CIDRAP News Aug. 13, 2021.
177 TVR Staff. Oxford Begins COVID-19 Vaccine Trials to Meet September Deadline. The Vaccine Reaction Apr. 27, 2020.
178 TVR Staff. Oxford Begins COVID-19 Vaccine Trials to Meet September Deadline. The Vaccine Reaction Apr. 27, 2020.
179 Folegatti PM., Ewer KJ. Aley PK., et.al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS CoV-2: a preliminary report of a phase 1/2 single-blind, randomized, controlled trial. The Lancet Aug 2020;396(10249):467-478.
180 Cáceres B. AstraZeneca Halts, Resumes COVID-19 Vaccine Trial After Serious Neurological Event. The Vaccine Reaction Sept. 14, 2020.
181 Cáceres B. AstraZeneca Halts, Resumes COVID-19 Vaccine Trial After Serious Neurological Event. The Vaccine Reaction Sept. 14, 2020.
182 Reuters. AstraZeneca's Japanese COVID-19 vaccine trial back up, U.S. still paused. MSN Oct. 2, 2020.
183 Scherer S. Canada joins countries in real-time AstraZeneca COVID vaccine review. Yahoo News Oct. 2, 2020.
184 Burton TM., Loftus P. Pivotal Studies of Covid-19 Vaccines From AstraZeneca, J&J Resuming. The Wall Street Journal Oct. 23, 2020.
185 Reuters. COVID-19 vaccine roll-out expected in less than 3 months in UK: The Times. Yahoo News Oct. 2, 2020.
186 Villafana T. ACIP Presentation: AstraZeneca COVID-19 vaccine (AZD1222). U.S. Centers for Disease Control & Prevention Jan. 27, 2021.
187 Burger L, Aripaka P. European regulator gives green light for Astra-Oxford COVID-19 vaccine. Reuters Jan. 29, 2021.
188 Cohen J. South Africa suspends use of AstraZeneca’s COVID-19 vaccine after it fails to clearly stop virus variant. Science Feb. 8, 2021.
189 Picheta R. AstraZeneca says “no evidence” of bloodclot risk from vaccine as countries suspend its use. CNN March 12, 2021.
190 World Health Organization. Statement of the WHO Global Advisory Committee on Vaccine Safety (GACVS) COVID-19 subcommittee on safety signals related to the AstraZeneca COVID-19 vaccine. Mar. 19, 2021.
191 Ljunggren D, Martell A. Canada pauses AstraZeneca COVID-19 vaccine use for those under 55, wants new risk analysis. Reuters Mar. 29, 2021.
192 Halasz S, Isaac L, Kappeler I, Woodyatt A. Germany will limit AstraZeneca vaccine to people over 60. CNN Mar. 30, 2021.
193 European Medicines Agency. AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets. Apr. 7, 2021.
194 European Medicines Agency. AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets. Apr. 7, 2021.
195 Greinacher A, Selleng K, Wesche J. et al. Towards Understanding ChAdOx1 nCov-19 Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT). Research Square Apr. 20, 2021.
196 Goodman B. Scientists Find How AstraZeneca Vaccine Causes Clots. WebMD Apr. 22, 2021.
197 European Medicines Agency. AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets. Apr. 7, 2021.
198 Reuters. Factbox-Some Countries Limit AstraZeneca Vaccine Use, U.S. Pauses J&J Shot. U.S. News & World Reports Apr. 19, 2021.
199 AstraZeneca vaccine: Denmark stops rollout completely. BBC News Apr. 14, 2021.
200 Goodman B. Scientists Find How AstraZeneca Vaccine Causes Clots. WebMD Apr. 22, 2021.
201 European Medicines Agency. COVID-19 vaccine safety update VAXZEVRIA AstraZeneca AB. Sept. 8, 2021.
202 Fisher BL, Raines K. Inovio COVID-19 Vaccine Uses Electricity to Drive DNA Into Body Cells. The Vaccine Reaction Apr. 18, 2020.
204 Fisher BL., Raines K. Inovio COVID-19 Vaccine Uses Electricity to Drive DNA Into Body Cells. The Vaccine Reaction Apr. 18, 2020.
206 INOVIO. Announces Positive Interim Phase 1 Data For INO-4800 Vaccine for COVID-19. June 30, 2020.
207 INOVIO. Announces Positive Interim Phase 1 Data For INO-4800 Vaccine for COVID-19. June 30, 2020.
208 Fisher BL., Raines K. Inovio COVID-19 Vaccine Uses Electricity to Drive DNA Into Body Cells. The Vaccine Reaction Apr. 18, 2020.
209 Clinical Trials. FDA places partial hold on Inovio’s Phase II/III Covid-19 vaccine trial. Sept. 29, 2020.
210 Roy M. Inovio expects to begin late-stage COVID-19 vaccine study in second quarter. Reuters Jan. 4, 2021.
211 McAuley AJ, Kuiper MJ, Durr PA, et al. Experimental and in silico evidence suggests vaccines are unlikely to be affected by D614G mutation in SARS-CoV-2 spike protein. npj Vaccines October 2020; 5: 96.
212 Tebas P, Yang SP, Boyer JD, et al. Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial. EClinicalMedicine January 2021; 31: 100689.
213 Carchidi A. Does Novavax Have What It Takes to Win the COVID-19 Vaccine Race? The Motley Fool May 24, 2020.
214 Goldman MC. Novavax Gains Following Promising Covid-19 Vaccine Trials. The Street Sept. 3, 2020.
215 Cáceres M. Novavax’s Adjuvanted COVID-19 Vaccine Caused Severe Adverse Reactions in Clinical Trials. The Vaccine Reaction Sept. 14, 2020.
216 Cáceres M. Novavax’s Adjuvanted COVID-19 Vaccine Caused Severe Adverse Reactions in Clinical Trials. The Vaccine Reaction Sept. 14, 2020.
217 Cáceres M. Novavax’s Adjuvanted COVID-19 Vaccine Caused Severe Adverse Reactions in Clinical Trials. The Vaccine Reaction Sept. 14, 2020.
218 Cáceres M. Novavax’s Adjuvanted COVID-19 Vaccine Caused Severe Adverse Reactions in Clinical Trials. The Vaccine Reaction Sept. 14, 2020.
219 Cáceres M. Novavax’s Adjuvanted COVID-19 Vaccine Caused Severe Adverse Reactions in Clinical Trials. The Vaccine Reaction Sept. 14, 2020.
220 Clinical Trials. Novavax launches Phase III trial of Covid-19 vaccine in UK. Sept. 25, 2020.
221 Manskar N Novavax COVID vaccine gets ‘fast track’ status from FDA. New York Post Nov. 9, 2020.
222 Loftus P. Novavax Vaccine Is 89% Effective Against Covid-19 in U.K. Study. The Wall Street Journal Jan. 28, 2021.
223 Novavax. Novavax Announces Memorandum of Understanding to Produce COVID-19 Vaccine Made in Canada. Feb. 2, 2021.
224 Takeda. Novavax and Takeda Announce Collaboration for Novavax’ COVID-19 Vaccine Candidate in Japan. Aug. 7, 2020.
225 European Medicines Agency. EMA starts rolling review of Novavax’s COVID-19 vaccine (NVX-CoV2373). Mar. 2, 2021.
227 Novavax. Novavax and Government of Switzerland Announce Agreement in Principle to Supply COVID-19 Vaccine. Feb. 3, 2021.
228 Novavax. Novavax Finalizes Agreement with Commonwealth of Australia for 51 Million Doses of COVID-19 Vaccine. Jan. 07, 2021.
229 Novavax. Novavax Announces Agreement with Government of New Zealand for 10.7 Million Doses of COVID-19 Vaccine. Dec. 16, 2020.
230 Novavax. Novavax and Government of Canada Finalize Advance Purchase Agreement for COVID-19 Vaccine. Jan. 22, 2021.
231 Formica N, Mallory R, Albert G, et al. Evaluation of a SARS-CoV-2 Vaccine NVX-CoV2373 in Younger and Older Adults. medRxiv Mar. 1, 2021.
233 Cáceres M., Fisher BL. 81 Percent of Clinical Trial Volunteers Suffer Reactions to CanSino Biologics’ COVID-19 Vaccine That Uses HEK293 Human Fetal Cell Lines. The Vaccine Reaction July 6, 2020.
234 Cáceres M., Fisher BL. 81 Percent of Clinical Trial Volunteers Suffer Reactions to CanSino Biologics’ COVID-19 Vaccine That Uses HEK293 Human Fetal Cell Lines. The Vaccine Reaction July 6, 2020.
235 Ma J. Coronavirus: Canada confirms planned Chinese vaccine trial has been scrapped after shipments delayed. South China Morning Post Aug 29, 2020.
236 Reuters Staff. CanSino to start Phase III trial of COVID-19 vaccine in Saudi. Reuters Aug. 9, 2020.
237 Ren D. CanSino gets Russia’s approval to start Covid-19 vaccine trials on humans after snubbing Canada. South China Morning Post Sept. 2, 2020.
239 Aguirre FA. CanSino, the Chinese vaccine that nobody talks about, begins its tests in southern Chile this Wednesday. LaTercera Dec. 15, 2020.
240 Drugs.com. CanSinoBIO Announces a Supply Agreement with Mexico on the Advance Purchase for COVID-19 Vaccine. Oct 15, 2020.
241 Margolis T. Mexico Approves Use of Unproven Chinese Covid Vaccine. Pulse News Mexico Feb. 11, 2021.
242 CTGN. Pakistan approves Chinese Sinopharm COVID-19 vaccine for emergency use. Jan. 20, 2021.
243 Paton J., Lyu D., Lauerman J. China’s Vaccine Front-Runner Aims to Beat Covid the Old-Fashioned Way. Bloomberg Businessweek Aug. 24, 2020.
244 Parpia R. China Administers Unlicensed Experimental COVID-19 Vaccines to Its Citizens. The Vaccine Reaction Oct. 5, 2020.
245 Hendler C. Brazil Halts and Re-Starts Phase 3 Clinical Trials of Chinese COVID-19 Vaccine. The Vaccine Reaction Nov. 24, 2020.
246 Reuters Staff. China approves Sinovac Biotech COVID-19 vaccine for general public use Reuters. Feb. 6, 2021.
248 AFP News. Brazil's Lula Receives First Dose Of Coronavirus Vaccine. International Business Times Mar. 13, 2021.
249 Pearson S, Magalhaes L. Study of Aggressive Covid-19 Strain in Brazil Suggests Limits of China Vaccine. The Wall Street Journal Times Mar. 6, 2021.
250 Precision Vaccinations. CoronaVac (Sinovac) COVID-19 Vaccine for Children. In: CoronaVac COVID-19 Vaccine. Sept. 27, 2021.
251 Precision Vaccinations. CoronaVac (Sinovac) COVID-19 Vaccine Side Effects. In: CoronaVac COVID-19 Vaccine. Sept. 27, 2021.
253 Logunov DY, Dolzhikova IV, Shcheblyakov DV et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia. Lancet 2021 Feb 20;397(10275):671-681.
254 Fedorinova Y, Kravchenko S. Russian Vaccine Team in Talks With China on Combination Trial. Bloomberg Feb. 5, 2021.
257 U.S. Food and Drug Administration. Coronavirus (COVID-19) Update: FDA Continues Important Work to Support Medical Product Development to Address New Virus Variants. Feb. 4, 2021.
258 Joseph A. Pfizer-BioNTech Covid-19 vaccine works just as well against variant first detected in U.K., study indicates. STAT News Jan. 20, 2021.
259 Kelland K. Study Suggests Pfizer's COVID-19 Vaccine Less Effective Against South African Variant. Reuters Feb. 3, 2021.
260 Attkisson S. STUDY: Vaccinated people more likely to be infected with Covid-19 variant. Apr. 16, 2021.
261 Lubell M. South African variant may evade protection from Pfizer vaccine, Israeli study says. Reuters Apr. 12, 2021.
264 Joseph A. Moderna’s vaccine is less potent against one coronavirus variant but still protective, company says. STAT News Jan. 25, 2021.
267 Cohen J. South Africa suspends use of AstraZeneca’s COVID-19 vaccine after it fails to clearly stop virus variant. Science Feb. 8, 2021.
268 U.S. Centers for Disease Control and Prevention. 05/05/2021: Lab Advisory: SARS-CoV-2 Variants B.1.617, B.1.617.1, B.1.617.2, and B.1.617.3 Classified as Variants of Interest. In: Division of Laboratory Systems (DLS). Apr. 12, 2021.
269 Dillon N. Highly contagious COVID B.1.617 variant first identified in India re-classified as ‘global concern,’ WHO says. New York Daily News May 10, 2021.
270 Public Health England. SARS-CoV-2 variants of concern and variants under investigation in England. Technical Briefing 15. June 11, 2021.
271 McGovern C. Death rate from variant COVID virus six times higher for vaccinated than unvaccinated, UK health data show. LifeSite News June 18, 2021.
272 Papenfuss M. Dangerous Delta COVID-19 Variant Infecting Vaccinated Adults In Israel. HuffPost June 25, 2021.
273 McNamara D. Pfizer to Seek OK for COVID Vaccine Booster Targeting Delta. WebMD July 8, 2021.
274 Lovelace Jr. B. Israel says Pfizer Covid vaccine is just 39% effective as delta spreads, but still prevents severe illness. CNBC July. 23, 2021.
275 U.S. Centers for Disease Control and Prevention. Vaccination to Prevent COVID-19 Outbreaks with Current and Emergent Variants — United States, 2021. In: Emergency Preparedness and Response. July 27, 2021.
276 McNamara D. Pfizer to Seek OK for COVID Vaccine Booster Targeting Delta. WebMD July 8, 2021.
278 Soucheray S. CDC, FDA recommend 3rd COVID vaccine dose for immune-compromised. CIDRAP Aug. 13, 2021.
279 U.S. Centers for Disease Control and Prevention. Joint Statement from HHS Public Health and Medical Experts on COVID-19 Booster Shots. In: CDC Newsroom. Aug. 18, 2021.
280 Phillips J. CDC Director: Annual COVID-19 Shots After Booster Not Expected. The Epoch Times Aug. 19, 2021.
281 Soucheray S. FDA signals apprehension about COVID-19 vaccine booster shots. CIDRAP News Sept. 16, 2021.
282 Schnirring L. FDA advisors OK Pfizer COVID booster for seniors, high-risk groups. CIDRAP News Sept. 17, 2021.
283 U.S. Food and Drug Administration. FDA Authorizes Booster Dose of Pfizer-BioNTech COVID-19 Vaccine for Certain Populations. Sept. 22, 2021.
284 Goodman B. CDC Chief Overrules Panel, OKs Boosters for Healthcare Workers. Medscape Sept. 23, 2021.
285 Stieber Z. Effectiveness of Some COVID-19 Vaccines Has Dropped Significantly: Study. The Epoch Times Aug. 12, 2021.
286 Nanduri S, Pilishvili T, Derado G, et al. Effectiveness of Pfizer-BioNTech and Moderna Vaccines in Preventing SARS-CoV-2 Infection Among Nursing Home Residents Before and During Widespread Circulation of the SARS-CoV-2 B.1.617.2 (Delta) Variant — National Healthcare Safety Network, March 1–August 1, 2021. MMWR ePub: Aug. 18, 2021.
287 The National Academies of Sciences, Engineering, and Medicine. National Academies Release Framework for Equitable Allocation of a COVID-19 Vaccine for Adoption by HHS, State, Tribal, Local, and Territorial Authorities. News Release Oct. 2, 2020.
288 Cáceres M. How Will Unhealthy Americans React to COVID-19 Vaccines? The Vaccine Reaction Oct. 5, 2020.
289 Dooling K, McClung N, Chamberland M, et al. The Advisory Committee on Immunization Practices’ Interim Recommendation for Allocating Initial Supplies of COVID-19 Vaccine — United States, 2020. MMWR Dec. 11, 2020; 69(49):1857-1859.
290 Dooling K, Marin M, Wallace M, et al. The Advisory Committee on Immunization Practices’ Updated Interim Recommendation for Allocation of COVID-19 Vaccine — United States, December 2020. MMWR Jan. 1, 2021; 69(5152):1657-1660.
292 Soucheray S. CDC, FDA recommend 3rd COVID vaccine dose for immune-compromised. CIDRAP Aug. 13, 2021.