Maternal administration of RSVpreF Vaccine Prevents RSV Infection in Infants: NEJM

RSV is a common and pervasive cause of acute respiratory illness. The virus is highly contagious and affects the lungs and airways. Infections occur in people of all ages and can feel like the common cold for most young adults, but for infants, the immunocompromised, and older adults, it can be potentially life-threatening.

In November 2018, the FDA granted Fast Track status to RSVpreF for the prevention of RSV-associated lower respiratory tract illness in infants by active immunization of pregnant women. However, the efficacy, immunogenicity, and safety of a bivalent RSVpreF vaccine in pregnant women and their infants are uncertain. Therefore, researchers of Pfizer conducted a study to assess the efficacy, safety, and immunogenicity of RSVpreF in infants born to healthy women vaccinated during pregnancy, as well as the safety and immunogenicity in the pregnant women.

It was a phase 2b randomized study, in which the researchers randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 μg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety endpoints and immunogenicity endpoints. In an interim analysis, the researchers assessed 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical cord blood, as well as maternal-to-infant transplacental transfer ratios.

Key findings of the study:

• In the planned interim analysis, the researchers included 406 women and 403 infants, among which 327 women (80.5%) received RSVpreF vaccine.
• They reported that most postvaccination reactions were mild to moderate.
• However, they noted that the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide.
• They noted that the incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants.
• They observed that the geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies.
• They found that the transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations.
• They further noted that across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios.

The authors concluded, "RSVpreF vaccine-elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. We found evidence of an acceptable safety profile for the RSVpreF vaccine in maternal recipients and their infants, elicitation of neutralizing antibody responses to RSVpreF vaccine in pregnancy, and efficient transfer of neutralizing antibodies to infants. Our trial also showed preliminary evidence of the efficacy of maternal vaccination with RSVpreF vaccine during pregnancy in preventing RSV-associated lower respiratory tract illness in infants."

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DOI: https://www.nejm.org/media/doi/full/10.1056/NEJMoa2106062