An RSV Vaccine During Pregnancy

The CDC recently recommended an RSV vaccine for pregnant women

On September 22, 2023, the CDC recommended a maternal vaccine made by Pfizer to prevent respiratory syncytial virus (RSV) to be given during the third trimester. Because RSV is a winter disease, the vaccine is best given between September and January. Every year in the United States, babies are hospitalized when RSV infects their windpipes, causing croup, or their small breathing tubes, causing wheezing (bronchiolitis), or their lungs, causing pneumonia. Most of these hospitalizations occur in babies who were previously healthy.

Because babies are often infected in the first few months of life—before they can be effectively vaccinated—one strategy to protect them would be to vaccinate their mothers. Antibodies induced in the mother would then be actively transported across the placenta, protecting the babies for the first 4 – 6 months of life, when they are most vulnerable.

The pivotal trial of Pfizer’s RSV vaccine included about 7,000 people given either the vaccine (which consisted of 120 micrograms of one RSV protein, called the fusion or F protein) or placebo. Protective efficacy against RSV disease was 80 percent for the first 3 months of life and 70 percent for the first 6 months.

When the FDA and CDC considered this vaccine, safety was an issue. That’s because Pfizer wasn’t the only company making an RSV vaccine for pregnant women. GlaxoSmithKline (GSK) also made a vaccine that was virtually identical to Pfizer’s (i.e., 120ug of the RSV F protein, unadjuvanted). GSK, however, abandoned their maternal RSV vaccine because of a concern about an increase in premature births in the vaccinated group.

When two companies make virtually identical vaccines, and one of them has a problem, two possibilities exist. Either both have a problem—and one of them hasn’t realized it yet—or neither have a problem. Indeed, although it wasn’t statistically significant, 33 more cases of prematurity occurred in Pfizer’s vaccine group than the placebo group. All cases occurred more than one month after receiving the vaccine. Although this difference wasn’t statistically significant, it was worrisome enough to the FDA that although Pfizer had asked for a license to administer the vaccine between 24 and 36 weeks of gestation, the license was granted only for 32 to 36 weeks of gestation. By limiting licensure to third trimester use, the FDA lessened the impact of prematurity should it be found in post-licensure studies.

Expectant parents deciding about Pfizer’s vaccine should consider the following: 1) every year in the United States, RSV causes 1.5 million out-patient visits, 500,000 emergency department visits, 80,000 hospitalizations, and 100-300 deaths, almost entirely in young infants; 2) during Pfizer’s vaccine trial, excess cases of prematurity in those vaccinated between 32 and 36 weeks of gestation were uncommon and not statistically significant; 3) there is another option; nirsevimab (Beyfortus), a long-acting monoclonal antibody, is highly effective at preventing RSV and is now recommended by the CDC for all babies up to 8 months of age as a single intramuscular injection before the RSV season.

No choice is risk-free. Everyone on the planet is infected with RSV by the time they are 5 years old. For the youngest babies, this infection can be devastating. Large, rigorous post-licensure surveillance programs are now in place to determine whether Pfizer’s maternal RSV vaccine is a rare cause of prematurity.