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 Foundation1 and World Health Organization (WHO)2 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.3
Vaccine Development Hampered by Enhanced Respiratory Disease
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in SARS-CoV-1 and MERS-CoV vaccines, but also with vaccines using formalin-inactivation for measles (this vaccine was withdrawn in 1967) and respiratory syncytial virus (RSV) vaccines.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.4
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.5 6
COVID-19 Vaccine Development Efforts
By mid-March and early April 2020, the WHO, National Institutes of Health7 universities,8 and global pharmaceutical corporations9 had announced development of more than 50 experimental COVID-19 vaccines.10 11
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.12
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.”13
The Biomedical Advanced Research and Development Authority (BARDA) was created by Congress in 2006 under the Pandemic and All Hazards Preparedness Act,14 legislation that has given billions of dollars to DHHS since then to develop “bioterrorism” and pandemic influenza vaccines.15 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.16
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.17
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.”18
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.19
"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."
U.S. Food and Drug Administration Vaccine Approval process
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.20
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.21
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.”22
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.23 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.”24
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.25
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.26
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.27 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.28
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.29
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.30
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.31
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.32
Gene-Based Vaccines and Traditional Vaccines
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.33 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.34
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.35 36
COVID-19 mRNA Vaccine Development
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.37 38 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.” 39
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.40
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.41
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.42 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.” 43
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.”44
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.45
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.”46
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.47
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-19.48
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.49 However, on October 22, 2020, Moderna reported that it had completed enrollment of trial participants and had recruited 11,000 participants from ethnically diverse communities50 and participants between 18 and 65 years of age with underlying conditions.51
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.52
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.53
Reports of 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.54
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.55
According to the federal vaccine adverse event reporting system (VAERS), as of April 23, 2021 there were a total of 48,192 reports submitted to VAERS associated with the experimental Moderna COVID-19 vaccines. Noted within these reports were 1,701 deaths, 668 permanent disabilities, 3,577 hospitalizations, 5,996 emergency room visits, and 998 life threatening events.56 Of the deaths reported to VAERS, 352 were noted as senior living administration settings,57 with 78 percent of overall reported deaths occurring in persons 65 years of age and older.58
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.59
Moderna has announced that it is anticipating $18.4 billion in sales from its COVID-19 vaccine in 2021.60
Pfizer-BioNTech COVID-19 Vaccine
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).61
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.”62
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.63
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 2021.64
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.65 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.67 Pfizer-BioNTech applied for Emergency Use Authorization (EUA) approval from the FDA on November 20, 202068 and received EUA approval on December 11, 2020 for use in persons 16 years of age and older.69
The experimental vaccine was previously granted EUA status in the U.K. on December 2, 202070 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.71
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.72
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.73
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.74
By April 23, 2021, reports submitted to VAERS for the Pfizer-BioNTech’s experimental COVID-19 vaccine for serious vaccine adverse events were over 5,653. Noted within these reports were 1,611 deaths, 738 permanent disabilities, 3,601 hospitalizations, 2,289 emergency room visits, and 898 life threatening events.75 Also noted in these reports were 359 deaths categorized as senior living administration,76 with 71 percent of reported deaths occurring in persons 65 years of age and older.77
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.78 Deaths following the Pfizer-BioNTech COVID-19 vaccine were also reported in Israel,79 Germany,80 Portugal and Switzerland.81
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.82 In January 2021, the FDA officially granted Pfizer’s request to update the EUA Fact Sheet to clarify that each vial contained six doses.83
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.84
In April 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. Pfizer has also reported that studies have reported the vaccine to be 93.1 percent effective six months after the second dose is administered.85
Pfizer has reported that their expected 2021 earnings from COVID-19 sales are estimated at $15 billion dollars.86
Dosing Schedules for mRNA COVID-19 vaccines
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-19.87
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:88
“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 April 24, 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.89 Preliminary results are expected by early summer 2021 but the study is expected to continue for at least one year.90
Janssen/Johnson & Johnson COVID-19 Vaccine
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 2020.91 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.92 93 PER.C6 are proprietary cells owned by Janssen Pharmaceutical that were developed in 1985 from retinal cells of an 18-week-old aborted fetus.94
The Janssen/Johnson & Johnson experimental COVID-19 vaccine entered Phase 2 trials in Spain in mid-September 2020.95 Clinical trials, however, were halted on October 12, 2020 after a participant developed an “unexplained illness.”96 Sources familiar with the event reported that a male in his 20’s had a stroke after receiving the experimental vaccine.97 Clinical trials in the U.S resumed in late October 2020.98
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.99
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.100
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.101
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.102
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 49.103 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.104 105
On April 23, 2021, the FDA updated the Janssen/Johnson & Johnson’s COVID-19 Fact Sheet and acknowledged that:106
“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.”
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.107
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.108
As of April 23, 2021 vaccine adverse events submitted to VAERS totaled 25,084, with 14,481noted as serious. Included in these reports were 214 deaths, 186 permanent disabilities, 2,896 emergency room visits, and 936 hospitalizations.109
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.110
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.111
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.”112
On April 20, 2021, Johnson & Johnson reported $100 million in first quarter earnings from its COVID-19 vaccine.113 Company officials have reported that annual vaccine doses will likely be needed for several years.114
Ongoing Vaccine Development
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.115
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).116
Preliminary results of the AstraZeneca’s Phase 1 and Phase 2 trials were published in July 2020 in The Lancet.117 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.118 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.119
While clinical trials resumed quickly in several countries including Great Britain, Japan, South Africa, India,120 and Canada, 121 trials in the U.S. remained on hold until October 23, 2020. 122
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.123
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.124
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.125
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.126
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.127
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.128
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.129 On March 30, 2021, Germany limited its use to persons over the age of 60.130
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.131
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.132
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.”133
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.134 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.135
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.136
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.137
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-2138 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. 139 140
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.141
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.142 143 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.144 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.145
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.146
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.147
Novavax COVID-19 Vaccine
Maryland-based Novavax Inc, a biotechnology company which has never successfully delivered a product to market,148 has developed an experimental vaccine using recombinant nanoparticle technology. Referred to as a protein subunit vaccine,149 NVX‑CoV2373 contains Novavax’s patented saponin-based Matrix-M™ adjuvant designed to enhance the immune response and stimulate high levels of neutralizing antibodies.150
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.151
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.152 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.153
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.154
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.155
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.156
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 variant was most predominant.157
By February 2021 Novavax had secured a memorandum of understanding with Canada158 and Takeda Pharmaceutical Company Ltd.159 (Japan) to produce the vaccine, while the European Medicines Agency (EMA) started their rolling reviews of the experimental vaccine.160 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);161 Switzerland;162 Australia;163 New Zealand;164 and Canada.165
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.166 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.167
COVID-19 Vaccine Development in China
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.168
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.169 This agreement, however, was scrapped in late August due to shipping delays.170
By December of 2020, Convidicea clinical trials had been launched in Saudi Arabia,171 Moscow,172 Mexico,173 and Chile,174 with advanced purchase agreements totaling 35 million doses.175
Pakistan and Mexico approved Convidicea under emergency prior to approval by any international health organizations and completion of Phase 3 trials in early 2021.176 177
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.178
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.179
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.180
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 2021.181 As March 2021 began, CoronaVac is in use or scheduled for use in Tunisia, the Philippines, Mexico, Malaysia, Turkey, Indonesia.182 Brazil followed suit in March 2020,183 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.184
Russian COVID-19 Vaccine Development
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.185
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-2.186
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.187
By March 2021, Sputnik V vaccine distribution agreements spanned more than 50 countries.188
COVID-19 Variants and Vaccines
Since the fall of 2020, multiple variants of the SARS-CoV-2 virus have emerged.189 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.”190
Pfizer-BioNTech reports its COVID-19 vaccine to be just as effective against the U.K.’s B.1.1.7 as the earlier variant of SARS-CoV-2 virus.191 The vaccine, however, appears to be less effective against the South African B.1.351 variant.192 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 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.193 194
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 is aimed at learning more on 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.195
Additionally, company officials reported that they were in discussions with the FDA and the European Medicines regarding plans for a clinical study of variant specific vaccines, including a vaccine targeting the South African B.1.351 variant.196
Moderna reports that its COVID-19 vaccine appears to offer vaccine-acquired protection against the U.K’s B.1.1.7 variant. The vaccine, however, had a six-fold reduction against the South African B.1.351 variant when compared to the initial SARS-CoV-2 virus.197
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 variant. Additionally, Moderna stated that they were planning to move forward with two unique study strategies.198
First, Moderna reportedly plans to evaluate three approaches to boosters. These include: clinical trials of a booster dose of a vaccine targeting the South African B.1.351 variant; clinical trials of a multi-variant vaccine dose targeting the original SARS-CoV-2 virus and the South African B.1.351 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 variant dose and the experimental multi-variant vaccine dose as a primary vaccination series in persons who are seronegative for SARS-CoV-2.199
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 variant, which is most common SARS-CoV-2 virus variant circulating in South Africa.200
COVID-19 Vaccine Allocation
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.”201
- 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 distributes COVID-19 vaccines to individuals with underlying health conditions and morbidities that have 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 are not being tested on these at risk populations. In real-world terms, because experimental COVID-19 vaccine clinical trials are not conducted with healthy individuals, the potential for vaccine adverse events in at-risk populations are unknown and not reported vaccines are in use in when generalized to for use in accordance with the allocation plan within the general population.202
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.203
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.204
On April 22, 2021, the CDC announced that COVID-19 vaccine availability was widely accessible and stated that all persons 16 years of age and older were now eligible to receive the vaccine.205
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.
« Return to Vaccines & Diseases Table of Contents
Updated April 28, 2021
1 Gates Foundation. Bill & Melinda Gates Foundation Dedicates Additional Funding to the Novel Coronavirus Response. Gates Foundation Press Release Feb. 5, 2020.
2 World Health Organization. World experts and funders set priorities for COVID-19 research. WHO Press Release Feb. 12, 2020.
3 Moran N. WHO releases COVID-19 roadmap funding efforts in progress. BioWorld Mar. 9, 2020.
4 Tregoning JS, Brown ES, et al. Vaccines for COVID-19. Clin Exp Immunol. 2020 Nov;202(2):162-192.
5 Mercola J. Will New COVID Vaccine Make You Transhuman? The Vaccine Reaction Sept. 29, 2020.
6 Tregoning JS, Brown ES, et al. Vaccines for COVID-19. Clin Exp Immunol. 2020 Nov;202(2):162-192.
7 National Institutes of Health. NIH clinical trial of investigational vaccine for COVID-19 begins. NIH Press Release Mar. 16, 2020.
8 University of Pittsburgh. COVID-19 Vaccine Candidate Shows Promise. Schools of the Health Sciences Press Release Apr. 2, 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. Press Release Mar. 24, 2020.
10 World Health Organization. Draft landscape of COVID-19 candidate vaccines. Feb. 26, 2021.
11 Cohen J. Vaccine designers take first shots at COVID-19. Science Magazine Apr. 3, 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'. Press Release 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. Nov. 18, 2020.
22 U.S. Food and Drug Administration. Emergency Use Authorization. Feb. 27, 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 Cohen J. Vaccine designers take first shots at COVID-19. Science Magazine Apr. 3, 2020.
34 Rauch S., Jasny E. et al. New Vaccine Technologies to Combat Outbreak Situations. Front Immunol 2018; 9:1963.
35 Fisher BL Raines K. Inovio COVID-19 Vaccine Uses Electricity to Drive DNA Into Body Cells. The Vaccine Reaction Apr. 18, 2020.
36 Cross R. Will the coronavirus help mRNA and DNA vaccines prove their worth? Chemical and Engineering News Apr. 3, 2020.
37 Cross R. Will the coronavirus help mRNA and DNA vaccines prove their worth? Chemical and Engineering News Apr. 3, 2020.
38 Horizon Magazine. Five things you need to know about mRNA vaccines. Apr. 1, 2020.
39 King A. RNA vaccines are coronavirus frontrunners. Chemistry World Mar. 11, 2020.
40 Horizon Magazine. Five things you need to know about mRNA vaccines. Apr. 1, 2020.
41 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.
42 ABNewswire. Scientists Test Potential Coronavirus Vaccine Straight on Humans Skipping Mice Trials. Benzinga Mar. 31, 2020.
43 Moderna, Inc. Moderna’s Work on a Potential Vaccine Against COVID-19. Mar. 30, 2020.
44 Cross R. Will the coronavirus help mRNA and DNA vaccines prove their worth? Chemical and Engineering News Apr. 3, 2020.
45 Moderna Inc. Moderna Announces Positive Interim Phase 1 Data for its mRNA Vaccine (mRNA-1273) Against Novel Coronavirus. Press Release May 18, 2020.
46 U.S. Department of Health & Human Services. Common Terminology Criteria for Adverse Events (CTCAE). Nov. 27, 2017.
47 National Institutes of Health - National Institute of Allergy and Infectious Diseases (NIAID). Phase 3 clinical trial of investigational vaccine for COVID-19 begins. News Release July 27, 2020.
48 National Institutes of Health - National Institute of Allergy and Infectious Diseases (NIAID). Phase 3 clinical trial of investigational vaccine for COVID-19 begins. News Release July 27, 2020.
49CBS2’s Dr. Max Gomez Explains Why Moderna’s COVID Vaccine Trial Has Been Slowed. CBS2 New York Oct. 7, 2020.
50 Guzman J. Moderna completes enrollment for its COVID-19 vaccine trial. The Hill Oct. 22, 2020.
51 Moderna. Slide 4: © 2020 ModernaSlide4Risk factors for severe COVID-19 disease. In: Moderna Cove Study. Oct. 21, 2020.
52 Dall C. Early data show Moderna's COVID vaccine 94.5% effective. CIDRAP News Nov. 16, 2020.
53 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. News Release Dec. 18, 2020.
54 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.
55 Cáceres M. Hammerin’ Hank’s COVID-19 Vaccination: A “Double-Edged Sword”? The Vaccine Reaction Jan. 31, 2021.
56 MedAlerts.org. COVID-19 Moderna serious vaccine adverse event reports – Feb. 28, 2021. In: VAERS data set 3/26/2021.
57 MedAlerts. Search Results: Apr 23, 2021 VAERS Dataset – Moderna COVID-19 Vaccine Serious Reports Submitted to VAERS on/before Mar. 31, 2021.
58 MedAlerts. Search Results: Apr. 23, 2021 VAERS Dataset – Moderna COVID-19 Cases Submitted to VAERS on/before Mar. 31, 2021.
59 Ellis R. Pfizer, Moderna Say Booster Shots Probably Needed. WebMD Brief. April 16, 2021.
60 Parpia R. Moderna Expects $18.4 Billion in Sales from Its COVID-19 Vaccine This Year. The Vaccine Reaction Mar. 21, 2021.
61 TVR Staff. Pfizer and BioNTech Begin Human Clinical Trials of COVID-19 Vaccine in U.S. The Vaccine Reaction May 25, 2020.
62 TVR Staff. Pfizer and BioNTech Begin Human Clinical Trials of COVID-19 Vaccine in U.S. The Vaccine Reaction. May 25, 2020.
63 TVR Staff. Pfizer/BioNTech’s COVID-19 Vaccine Causes Adverse Reactions in Over Half of Clinical Trial Volunteers. The Vaccine Reaction July 18, 2020.
64 BusinessWire. Pfizer and BioNTech Choose Lead mRNA Vaccine Candidate Against COVID-19 and Commence Pivotal Phase 2/3 Global Study. July 27, 2020.
65 BusinessWire. Pfizer and BioNTech Propose Expansion of Pivotal COVID-19 Vaccine Trial. Press Release Sept. 12, 2020.
66 Reuters. Coronavirus vaccine study by Pfizer shows mild-to-moderate side effects. Fox Business Sept. 15, 2020.
67 Pfizer. PFIZER AND BIONTECH ANNOUNCE VACCINE CANDIDATE AGAINST COVID-19 ACHIEVED SUCCESS IN FIRST INTERIM ANALYSIS FROM PHASE 3 STUDY. Nov. 9, 2020.
68 Chander V. Pfizer files COVID-19 vaccine application to U.S. FDA. Reuters Nov. 20, 2020.
69 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.
70 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.
71 Smout A UK issues anaphylaxis warning on Pfizer vaccine after adverse reactions. Reuters Dec. 9, 2020.
72 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.
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