Three Dose Levels of a Maternal Respiratory Syncytial Virus Vaccine Candidate Are Well Tolerated and Immunogenic in a Randomized Trial in Nonpregnant Women

Abstract

Background: Respiratory syncytial virus (RSV) causes respiratory tract infections, which may require hospitalization especially in early infancy. Transplacental transfer of RSV antibodies could confer protection to infants in their first months of life.

Methods: In this first-in-human, placebo-controlled study, 502 healthy nonpregnant women were randomized 1:1:1:1 to receive a single dose of unadjuvanted vaccine containing 30/60/120 µg of RSV fusion (F) protein stabilized in the prefusion conformation (RSVPreF3) or placebo.

Results: Solicited local adverse events (AEs) were more frequently reported in the RSVPreF3 groups (4%-53.2%) versus placebo (0%-15.9%); most were mild/moderate. Unsolicited AEs were comparably reported among groups. Three serious AEs were reported; none was vaccination-related. Compared with prevaccination values, anti-RSV A neutralizing antibody geometric mean titers and anti-RSVPreF3 immunoglobulin G geometric mean concentrations increased 8- to 14-fold and 12- to 21-fold at day 8 and persisted 5- to 6-fold and 6- to 8-fold higher until day 91 in the RSVPreF3 groups versus 1-fold in placebo. Comparisons at day 8 and day 31 showed that the higher dose levels were significantly more immunogenic than the lowest one.

Conclusions: The RSVPreF3 vaccine was well tolerated and immunogenic. The 60 and 120 µg dose levels were selected for further investigation in pregnant women.

Clinical trials registration: NCT03674177.

Keywords: RSV; RSV vaccine; immunogenicity; maternal vaccine; nonpregnant women; respiratory syncytial virus; safety; vaccination.

Figure 1.

Plain language summary.

Figure 2.

Participant flow chart. Abbreviations: 30 RSVPreF3/60 RSVPreF3/120 RSVPreF3, group receiving 1 dose of the RSV vaccine containing 30, 60, or 120 µg of RSVPreF3 antigen; D, day; n, number of women; placebo, group receiving 1 dose of placebo; RSV, respiratory syncytial virus.

Figure 3.

Incidence of solicited local and general adverse events from day 1 to day 7 postvaccination (exposed set). Error bars indicate 95% confidence intervals. Abbreviations: 30 RSVPreF3/60 RSVPreF3/120 RSVPreF3, group receiving 1 dose of the RSV vaccine containing 30, 60, or 120 µg of RSVPreF3 antigen; GI, gastrointestinal; placebo, group receiving 1 dose of placebo; RSV, respiratory syncytial virus.

Figure 4.

Anti-RSV A neutralizing antibody geometric mean titers (neutralization assay [ED60]; per protocol set). Error bars indicate 95% confidence intervals. Abbreviations: 30 RSVPreF3/60 RSVPreF3/120 RSVPreF3, group receiving 1 dose of the RSV vaccine containing 30, 60, or 120 µg of RSVPreF3 antigen; ED60, serum dilution inducing 60% reduction in plaque-forming units; GMTs, geometric mean titers; placebo, group receiving 1 dose of placebo; RSV, respiratory syncytial virus.

Figure 5.

Anti-RSVPreF3 IgG antibody geometric mean concentrations (enzyme-linked immunosorbent assay [EU/mL]; per protocol set). Error bars indicate 95% confidence intervals. Abbreviations: 30 RSVPreF3/60 RSVPreF3/120 RSVPreF3, group receiving 1 dose of the RSV vaccine containing 30, 60, or 120 µg of RSVPreF3 antigen; EU, laboratory units of enzyme-linked immunosorbent assay; GMCs, geometric mean concentrations; IgG, immunoglobulin G; placebo, group receiving 1 dose of placebo; RSV, respiratory syncytial virus.