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. In June 2024, the CDC’s ACIP committee revised their RSV vaccine guidance and recommended that adults 60 through 74 years considered at high-risk for severe RSV illness and all adults 75 years and older receive a single dose of RSV vaccine.
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.
