Every year in the United States, respiratory syncytial virus (RSV) causes about 1.5 million outpatient visits, 500,000 emergency department visits, 70,000 hospitalizations, and 100-300 deaths in children less than 5 years of age. Most of the hospitalizations and deaths occur in children less than 6 months of age. For that reason, both Pfizer and GSK stepped forward to make an RSV vaccine for people during pregnancy. Antibodies generated during pregnancy would then be passively transferred to the baby, offering protection for infants during the time when they are most vulnerable to the disease.
The Pfizer and GSK programs were similar. Both inoculated pregnant people with a single dose of 120 micrograms of the RSV prefusion protein between roughly 24 and 36 weeks of gestation. Pfizer studied about 7,000 pregnant people and GSK about 10,000. Both RSV vaccines were about 70% effective at preventing severe lower respiratory disease during the six-month follow-up period. In April 2023, Pfizer published the results of its phase 3 trial (Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F vaccine in pregnancy to prevent RSV illness in infants. N Engl J Med. 2023 Apr 20;388(16):1451-1464). In August 2023, the Food and Drug Administration (FDA) approved Pfizer’s RSV vaccine for pregnant people to prevent RSV-associated lower respiratory tract infections in infants less than 6 months of age. GSK, on the other hand, never submitted its product for licensure due to an increased incidence of premature births in the vaccine group.
On March 14, 2024, GSK published the results of its RSV trial in pregnant people (Dieussaert I, Kim JH, Luik S, et al. RSV prefusion F protein-based maternal vaccine—preterm birth and other outcomes. N Engl J Med. 2024 Mar 14;390(11):1009-1021). The target enrollment of about 10,000 people was not reached because the trial was stopped prematurely. Preterm births occurred in 6.8% of the infants in the vaccine group and 4.9% in the placebo group for a relative risk of 1.37 (confidence interval 1.08 to 1.74). This was a statistically significant difference (p=0.01). For every 54 infants born to people who received vaccine rather than placebo during pregnancy, one additional preterm birth occurred. This imbalance in preterm births was observed primarily in low- and middle-income countries when compared with high-income countries. The time from vaccination to preterm births varied from weeks to months, making it difficult to identify a particular mechanism for the problem.
Because it remains unclear why the GSK but not Pfizer vaccine was associated with preterm births, the FDA licensed Pfizer’s vaccine only for those who were in the third trimester—between 32 and 36 of weeks gestation. The reasoning was that if Pfizer’s vaccine was also found to be associated with preterm births, it would be less serious were it to occur in the third trimester than the second trimester. Time will tell whether the Pfizer vaccine has a similar problem. But to date, post-licensure monitoring hasn’t found this association.
Every year in the United States, respiratory syncytial virus (RSV) causes about 1.5 million outpatient visits, 500,000 emergency department visits, 70,000 hospitalizations, and 100-300 deaths in children less than 5 years of age. Most of the hospitalizations and deaths occur in children less than 6 months of age. For that reason, both Pfizer and GSK stepped forward to make an RSV vaccine for people during pregnancy. Antibodies generated during pregnancy would then be passively transferred to the baby, offering protection for infants during the time when they are most vulnerable to the disease.
The Pfizer and GSK programs were similar. Both inoculated pregnant people with a single dose of 120 micrograms of the RSV prefusion protein between roughly 24 and 36 weeks of gestation. Pfizer studied about 7,000 pregnant people and GSK about 10,000. Both RSV vaccines were about 70% effective at preventing severe lower respiratory disease during the six-month follow-up period. In April 2023, Pfizer published the results of its phase 3 trial (Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F vaccine in pregnancy to prevent RSV illness in infants. N Engl J Med. 2023 Apr 20;388(16):1451-1464). In August 2023, the Food and Drug Administration (FDA) approved Pfizer’s RSV vaccine for pregnant people to prevent RSV-associated lower respiratory tract infections in infants less than 6 months of age. GSK, on the other hand, never submitted its product for licensure due to an increased incidence of premature births in the vaccine group.
On March 14, 2024, GSK published the results of its RSV trial in pregnant people (Dieussaert I, Kim JH, Luik S, et al. RSV prefusion F protein-based maternal vaccine—preterm birth and other outcomes. N Engl J Med. 2024 Mar 14;390(11):1009-1021). The target enrollment of about 10,000 people was not reached because the trial was stopped prematurely. Preterm births occurred in 6.8% of the infants in the vaccine group and 4.9% in the placebo group for a relative risk of 1.37 (confidence interval 1.08 to 1.74). This was a statistically significant difference (p=0.01). For every 54 infants born to people who received vaccine rather than placebo during pregnancy, one additional preterm birth occurred. This imbalance in preterm births was observed primarily in low- and middle-income countries when compared with high-income countries. The time from vaccination to preterm births varied from weeks to months, making it difficult to identify a particular mechanism for the problem.
Because it remains unclear why the GSK but not Pfizer vaccine was associated with preterm births, the FDA licensed Pfizer’s vaccine only for those who were in the third trimester—between 32 and 36 of weeks gestation. The reasoning was that if Pfizer’s vaccine was also found to be associated with preterm births, it would be less serious were it to occur in the third trimester than the second trimester. Time will tell whether the Pfizer vaccine has a similar problem. But to date, post-licensure monitoring hasn’t found this association.