Read and report vaccine reactions, harassment and failures.
What is the history of Respiratory Syncytial Virus (RSV) vaccine in America?
In 1966, the first vaccine for Respiratory Syncytial Virus (RSV), a formalin-inactivated RSV vaccine, was administered to U.S. infants and children participating in four clinical trials. The vaccinated children were subsequently exposed to RSV in the community and those who had no antibodies against RSV infection prior to vaccination experienced more frequent and severe RSV infection, a condition known as enhanced respiratory disease. The affected infants and children presented with wheezing, bronchopneumonia and fever, with approximately 80 percent requiring hospitalization. Additionally, two toddlers who were vaccinated as infants died as a result of their enhanced illness.
As a result of the failed vaccine and harms caused to those who received this experimental vaccine, development of further vaccines to prevent RSV infection stalled for several decades. However, in recent years, several pharmaceutical companies have employed new strategies to develop a vaccine without the risk of enhanced disease.
One approach has been the development of a vaccine to target pregnant women in the hopes that maternal antibodies would be transferred to the infant and offer protection from illness. Strategies has also included the use of novel vaccine technologies such as gene-based vaccines, adjuvanted subunit vaccines, and more. RSV vaccines intended for older adults were also developed and put through clinical trials.
GlaxoSmithKline (GSK) RSV Vaccine
In October 2022, GlaxoSmithKline (GSK) pharmaceutical issued a press release that reported their RSV vaccine reduced severe RSV illness by 94.1 percent in persons 60 years and older. GSK also reported that the vaccine had an overall efficacy of 82.6 percent in their Phase 3 clinical trial. This vaccine combines a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) with GSK’s proprietary AS01E adjuvant. This adjuvant is a liposome-based adjuvant that contains two ingredients, 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and saponin QS-21, which stimulates the immune system. This adjuvant is also used in the Shingrix herpes zoster (shingles) vaccine, a vaccine that has been associated with an increased risk of Guillain-Barré syndrome (GBS).
While GSK reported their vaccine to be highly efficacious in reducing severe RSV illness in persons 60 years and older, the clinical trials were not sufficiently powered to estimate its efficacy against hospitalization and/or death. In the clinical trials, there were less than five cases of RSV infection and no associated deaths. Additionally, the clinical trial took place during a shift in the seasonal patterns of RSV infections attributed to the COVID-19 pandemic.
The initial clinical trials for GSK’s RSV vaccine were intended for pregnant women, however, trials were permanently halted due to an undisclosed safety signal with the vaccine product.
During the FDA’s Vaccines and Biologics Products Advisory Committee convened on March 1, 2023 to review GSK’s application for licensure, it was reported that one case of Guillain Barre Syndrome (GBS), a rare neurological disorder that causes inflammation of the peripheral nerves with complications that can include temporary or chronic paralysis, including full body paralysis, and may lead to death, had occurred among the 15,400 clinical trial participants. Additionally, there was a higher rate of vaccine recipients who experienced atrial fibrillation, a serious heart disorder that may lead to complications such as stroke, heart attack, or heart failure, in comparison to those who received the placebo.
GSK also reported that in one clinical trial, Study 007, which studied the use of the experimental RSV shot when given at the same time as the quadrivalent influenza vaccine, of the 442 participants, two cases of Acute Disseminating Encephalomyelitis (ADEM) had occurred, with one case resulting in death.
Despite the safety risks, most committee members voted to recommend the product for licensure. Those who voted against the vaccine expressed concerns regarding the case of GBS, as well as the ADEM safety signal when administered along with the flu vaccine. All committee members, however, voted to recommend the experimental RSV shot based on the vaccine’s effectiveness at preventing RSV acute respiratory illness and lower respiratory tract infection.
On May 3, 2023, the FDA licensed use of GSK’s AREXVY RSV vaccine for use in adults 60 years of age and older. The CDC’s Advisory Committee on Immunization Practices (ACIP) voted on June 21, 2023 to recommend use of the vaccine in all persons 60 years and older, based on “shared clinical decision-making”. This recommendation means that eligible individuals may choose to receive the vaccine if they believe that the benefits of vaccination outweigh the risks.
Pfizer RSV Vaccine
In August 2022, Pfizer issued a press release announcing the success of their Phase 3 clinical trial of a bivalent RSV prefusion F vaccine candidate, RSVpreF, in persons 60 years of age and older. According to Pfizer, this vaccine is comprised of equal amounts of recombinant RSV prefusion F from subgroups A and B, and was reported to be highly efficacious at preventing severe RSV illness. Company official also reported that the vaccine was well tolerated by clinical trial participants, and had no safety issues.
Safety concerns with the vaccine, however, were revealed at the VRBPAC meeting held on February 28, 2023 to review the clinical data submitted by Pfizer. During this meeting, it was reported that two cases of GBS had occurred during the clinical trial, at a rate of approximately 1 in 9,000. Additionally, one clinical trial participant who received the experimental RSV vaccine experienced a delayed allergic reaction, with complications that included shortness of breath, chest pain, and loss of consciousness.
As with the GSK RSV vaccine, there was a higher number of clinical trial participants who experienced atrial fibrillation after receipt of the vaccine when compared to those who got the placebo.
During this meeting, the FDA also revealed that the placebo used in the clinical trial consisted of the excipients used in the RSV vaccine, without the RSV antigens, and not a saline solution.
Despite the safety risks associated with the vaccine, and the lack of data to show that the vaccine would prevent hospitalization and deaths from RSV, especially among individuals most at risk for the illness, most VRBPAC committee members voted in favor of recommending the vaccine. Those who voted against the vaccine expressed concerns regarding both the vaccine’s safety and effectiveness.
In November 2022, Pfizer announced that their bivalent RSV prefusion vaccine candidate RSVpreF or PF-06928316 targeting pregnant women had an 81.8 percent efficacy against severe RSV illness in infants up to three months. This vaccine candidate is reported to produce antibodies that block the F protein of both RSV subgroup A and B to prevent infection. Pfizer’s clinical trial involved the administration of the experimental vaccine to pregnant women in their third trimester with the goal of offering protection to their newborn infants through maternal antibodies. While the vaccine was reported by Pfizer to be highly efficacious, they also acknowledged that the vaccine failed to reduce the number of infant medical appointments for RSV, including visits for non-serious infection.
Clinical trials of Pfizer’s RSV vaccine candidate commenced in June 2020 and was reported to have been conducted in 18 countries in both the northern and southern hemispheres through several RSV seasons. Approximately 7,400 pregnant women under the age of 49 were randomized 1:1 to receive either Pfizer’s RSVpreF vaccine candidate or a placebo at the end of the second trimester or during the third trimester. The women in the study were reportedly followed for safety for six months while their infants were studied for at least one year for efficacy and safety, with some followed for up to two years.
According to data presented by Pfizer during the February 2023 ACIP meeting, 3,682 pregnant women were administered a dose of the experimental RSV vaccine between 24 and 36 weeks gestation, with nearly 14 percent experiencing a vaccine adverse event, 4.2 percent of which were reported as serious, 1.7 percent reported as severe, and 0.5 percent as life-threatening.
Pfizer also reported that 37.1 percent of infants whose mothers received the vaccine were noted to have experienced an adverse event within one month of birth, 15.5 percent of which were considered serious, 4.5 percent as severe, and 1 percent as life-threatening. Pfizer’s data also noted an increased risk of premature and low birth weight for infants born to vaccinated pregnant women. The data also noted the death of one pregnant woman, and 18 fetal deaths (10 in the RSV vaccine group and 8 in the placebo) and 17 infant deaths (5 in the RSV vaccinated and 12 in the placebo group). Pfizer stated that all deaths were unrelated to the vaccine.
While the FDA’s VRBPAC committee voted unanimously in favor of the efficacy of the Pfizer’s ABRYSVO’s RSV vaccine for the prevention of RSV infection in infants whose mothers received the vaccine during pregnancy, four committee members voted against the vaccine as it pertained to the safety data provided by the manufacturer. Those who voted against the use of the vaccine in pregnant women expressed concern over the safety signals found in the clinical trials.
On May 31, 2023, the FDA licensed the ABRYSVO RSV vaccine for use in adults 60 years of age and older, for the prevention of lower respiratory tract disease caused by RSV. This vaccine received a “shared clinical decision-making” recommendation by the CDC’s ACIP on June 21, 2023. A “shared clinical decision-making” recommendation means that individuals 60 years and older may consider receiving a dose of the vaccine if they believe that the potential benefits from the vaccine outweigh the risks.
Pfizer’s ABRYSVO RSV vaccine received FDA approval on August 21, 2023 for use in pregnant women for the prevention of RSV disease in their newborns, to be given between 32- and 36-weeks gestation. In their press release, the FDA acknowledged that pregnant women who received this vaccine experienced higher rates of pre-eclampsia, a serious hypertensive disorder during pregnancy, and pre-term deliveries compared to those who received the placebo. Infants born to vaccinated women had higher rates of jaundice and lower birth weights. The FDA, however, reported that they were requiring Pfizer to complete “postmarketing studies to assess the signal of serious risk of preterm birth and to assess hypertensive disorders of pregnancy, including pre-eclampsia.”
On September 22, 2023, the CDC’s ACIP voted in favor of recommending ABRYSVO RSV vaccine for use in all pregnant women, to be given between 32- and 36-weeks gestation during the season when RSV is actively circulating. The CDC, however, states that pregnant women can decline RSV vaccine if they are planning to have their newborn receive a dose of nirsevimab monoclonal antibody.
In the recommendation for the use the Pfizer RSV vaccine in pregnant women for the prevention of RSV illness in their newborn infants, the CDC’s Advisory Committee on Immunization Practices noted that:
“For the GRADE assessment of harms, results from the phase 2b and phase 3 trials were pooled¶¶ (9,16). The overall evidence certainty using GRADE criteria was rated as very low, driven by the uncertainty in the critical harm outcome of preterm birth (<37 weeks’ gestation).*** ACIP judged the benefits of maternal RSVpreF vaccination at 32–36 weeks’ gestation to outweigh the potential risks for preterm birth and hypertensive disorders of pregnancy.”
GRADE (Grading of Recommendations Assessment, Development and Evaluation) is an evidence-based framework used by the CDC’s ACIP to assess the type or quality of evidence about a vaccine's expected health impacts and the balance of health benefits and risks, along with the values and preferences of persons affected, and health economic analyses.
According to the GRADE system used by the ACIP for evaluating evidence, very low certainty evidence means that confidence in the evidence is lacking and that The true effect is likely to be substantially different from the estimate of effect.
RSV Monoclonal Antibodies
On July 17, 2023 the FDA approved the drug nirsevimab under the trade name Beyfortus, a monoclonal antibody, for the prevention of RSV. Though the CDC has determined that it can define nirsevimab as a vaccine for their purposes, nirsevimab is not classified as a vaccine by the FDA, American Medical Association or the World Health Organization. On August 3, 2023, the CDC recommended that all infants under eight months of age born during, or entering their first RSV season (late fall through early spring, receive a single dose of Nirsevimab. Infants and young children ages 8 through 19 months who are considered to be at an elevated risk of severe RSV illness are also recommended to receive a dose during their second RSV season.
Nirsevimab is not routinely recommended for use in infants whose mothers received a dose of RSV vaccine during pregnancy. However, infants whose mothers received RSV vaccine during pregnancy may be given a dose under certain circumstances, at the discretion of their health care provider. These circumstances include infants born with congenital conditions that place them at high risk for severe RSV illness (congenital health disease, receipt of intensive care services, oxygen supplementation), those who underwent cardiopulmonary bypass, those born to mothers with immunocompromising conditions, and those born within two weeks of maternal RSV vaccination. No safety or effectiveness data exists on the use of Nirsevimab in infants whose mothers received RSV vaccination during pregnancy. To learn about nirsevimab, visit NVIC’s RSV Prevention and Treatment page.
IMPORTANT NOTE: NVIC encourages you to become fully informed about Respiratory Syncytial Virus (RSV) and the Respiratory Syncytial Virus (RSV) 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.