A bivalent protein-based vaccine against respiratory syncytial virus (RSV) administered during pregnancy was safe and led to higher neutralizing antibody responses in mothers, as well as evidence of protection in their infants, an interim analysis of a phase IIb trial found.

The geometric mean ratios of 50% neutralizing antibody titers against RSV A and B in maternal serum and umbilical cord blood were higher in vaccine recipients versus placebo recipients, reported Alejandra Gurtman, MD, of Pfizer in Pearl River, New York, and colleagues.

Moreover, post-vaccine adverse events (AEs) were mild or moderate, and no serious AEs were judged to be related to the vaccine, the authors wrote in the New England Journal of Medicine.

A post-hoc efficacy analysis showed an estimated vaccine effectiveness of 84.7% (95% CI 21.6-97.6) against medically attended RSV-associated lower respiratory tract illness, and 91.5% (95% CI -5.6 to 99.8) against severe RSV-associated lower respiratory tract illness, Gurtman and team noted.

There is no vaccine or therapy to specifically treat RSV, they added, and past vaccine candidates led to vaccine-mediated enhancement of disease in infants who had not been previously exposed to RSV infection. The authors hypothesized that since adults have been exposed, immunizing pregnant women could “passively protect infants” from RSV disease at birth, similar to influenza, tetanus, and pertussis vaccines.

This proof-of-concept trial examined the safety and immunogenicity of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine candidate among healthy pregnant women ages 18 to 49 at 24 to 36 weeks’ gestation in the U.S., Chile, Argentina, and South Africa.

Participants were randomized to receive either one or two doses of vaccine (120 μg or 240 μg) formulated with or without aluminum hydroxide, or to placebo.

This interim analysis included data on a cohort of 406 pregnant women from the U.S., who were vaccinated between August 14 and November 6, 2019, and 403 infants, with follow-up during the 2019-2020 RSV season.

Of the included women, 327 received the RSVpreF vaccine. Most women were white (80%), while 28% were Hispanic/Latina. Median age was 27, and median gestation was about 31 weeks.

All 406 women were included in the safety population, with an AE reporting period of 5.5 months. About 5% of vaccine recipients reported fever at a temperature of 38.0º C or higher, but none reported a fever over 38.9ºC.

In total, there were 55 serious AEs, 84% of which were related to “complications of pregnancy, labor, delivery, and the immediate postpartum period.” There was one stillbirth at 31 weeks in the placebo group, and the other serious AEs included appendicitis, gastroenteritis, pyelonephritis, and influenza. No serious AEs were judged to be related to the vaccine.

Among the 403 infants, the most common AE was neonatal jaundice or hyperbilirubinemia, and there were 15 preterm births. Serious AEs occurred in 94 infants, including congenital anomalies in 69. Almost 80% of these were considered to be mild and consistent with background rates. No serious AEs were judged to be related to the vaccine. Interestingly, three infants were hospitalized for acute respiratory illness, and two infants developed RSV infection.

Examining immunogenicity, transplacental neutralizing antibody titers were higher among those in the vaccine group without aluminum hydroxide than those with aluminum hydroxide, regardless of dose. Gurtman’s group also found that geometric mean titer ratios were similar, regardless of the time of immunization (24-36 weeks).

The post-hoc analysis for efficacy included 508 infants, 405 of whom had mothers in the vaccine group and 103 of whom had mothers who received placebo. Five infants in the placebo group had medically attended RSV-associated lower respiratory tract illness, three with severe illness. In the vaccine group, three infants had RSV, one with severe illness.

Since the interim analysis only included U.S. participants, these results may not be applicable to other countries, where transplacental transfer ratios were lower, Gurtman and team acknowledged. In addition, vaccine efficacy was based on post-hoc analyses.

Based on their results, a phase III trial of a 120 μg dose of RSVpreF without aluminum hydroxide is underway, they noted.

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