Investigators from multiple institutions conducted a planned interim analysis of data collected during a randomized controlled trial of a bivalent respiratory syncytial virus (RSV) prefusion F protein-based (RSVpreF) vaccine administered to pregnant women that is designed to prevent RSV disease in their infants. Study participants were pregnant women from the US, Chile, Argentina, and South Africa who were randomized 1:1:1:1:1 to receive RSVpreF, 120 μg or 240 μg, with or without aluminum hydroxide, or placebo, at 24-36 weeks’ gestation. Vaccination prior to the RSV season in each hemisphere was planned, and participants in the US were immunized from August 14 through November 6, 2019. After receiving the study vaccine, participants recorded adverse events daily for 7 days. Safety data on their infants also were collected. Surveillance for adverse events in infants is ongoing, with data collected through January 31, 2020 included in the current analyses. Blood was obtained from study participants and their infants at birth for 50% titers of RSV A, B, and combined A/B neutralizing antibodies. The ratio of titers in those in each of the active vaccine groups was compared to that of placebo recipients. For this interim analysis, results were descriptive only. An exploratory analysis of PCR-confirmed medically attended RSV illness and severe RSV illness (using a standardized definition) was conducted on all US participants, including some not in the primary study analyses, to estimate vaccine efficacy.
For the primary analysis, data were analyzed on 406 women and 403 infants; 327 women (80.5%) received active RSVpreF vaccine. Initial vaccine reactions, including pain, swelling, and redness at the injection site occurred almost exclusively in those receiving active vaccine and was more frequent in women who received RSVpreF with aluminum hydroxide; 5.1% of women receiving active vaccine had fever. Rates of other adverse events in mothers and infants were similar among those receiving active vaccine or placebo; none of the adverse events were thought to be related to vaccination. Ratios of neutralizing antibodies in women receiving RSVpreF, compared to placebo recipients, ranged from 11.0 to 15.1 for RSV A and 13.7 to 17.5 for RSV B. Corresponding ratios for their infants were 9.7 to 11.7 for RSV A and 13.6 to 16.8 for RSV B. Data on a total of 508 infants, including 405 whose mothers received RSVpreF, were included in the exploratory analysis. Among those whose mothers received active vaccine, 3 cases of medically attended RSV disease occurred, and 1 infant had severe disease. Conversely, 5 and 3 cases of medically attended and severe disease, respectively, occurred in 103 infants whose mothers received placebo. Based on these numbers, the estimated vaccine efficacy was 84.7% (95% confidence interval [CI], 21.6, 97.6) in preventing medically attended RSV disease and 91.5% (95% CI, -5.6, 99.8) for severe disease.
The authors concluded...