Immunogenicity and Safety of 3 Formulations of a Respiratory Syncytial Virus Candidate Vaccine in Nonpregnant Women: A Phase 2, Randomized Trial

Abstract

Background: Respiratory syncytial virus (RSV) is a common cause of respiratory tract illness and hospitalization in neonates and infants. RSV vaccination during pregnancy may protect offspring in their first months of life.

Methods: This randomized, observer-blind, multicenter, phase 2 study evaluated the immunogenicity and safety of an RSV candidate vaccine in healthy nonpregnant women aged 18-45 years. Four hundred participants were randomized (1:1:1:1) to receive a single intramuscular dose of vaccine containing 30 µg, 60 µg, or 120 µg of RSV fusion protein engineered to preferentially maintain a prefusion conformation (RSV-PreF vaccine) or placebo.

Results: Thirty days postvaccination, RSV-A neutralizing antibody geometric mean titers (GMTs) increased 3.75-, 4.42- and 4.36-fold; RSV-B neutralizing antibody GMTs 2.36-, 2.54- and 2.76-fold; and palivizumab competing antibody (PCA) concentrations 11.69-, 14.38- and 14.24-fold compared with baseline levels in the 30 µg, 60 µg, and 120 µg RSV-PreF groups, respectively. Antibody titers and PCA concentrations at day 30 were significantly higher with the 120 µg compared to the 30 µg RSV-PreF vaccine. All RSV-PreF vaccine formulations and the placebo had similar reactogenicity profiles. No serious adverse events were considered to be related to the RSV-PreF vaccine.

Conclusions: The 3 formulations of the investigational RSV-PreF vaccine were well-tolerated and induced RSV-A and RSV-B neutralizing antibodies and PCAs in healthy, nonpregnant women.

Clinical trials registration: NCT02956837.

Keywords: maternal immunization; neutralizing antibodies; nonpregnant women; palivizumab competing antibody; randomized trial; respiratory syncytial virus; safety.

Figure 1.

Study design and procedures. Enrollment stages reflect planned enrollment figures. Abbreviations: 30 RSV-PreF/60 RSV-PreF/120 RSV-PreF, group of women who received 1 dose of the unadjuvanted respiratory syncytial virus (RSV) vaccine containing 30, 60, or 120 μg of RSV prefusion F protein; Control, group of women who received 1 dose of placebo; iSRC, internal safety review committee.

Figure 2.

Flow of participants. *One participant was withdrawn due to a serious adverse event after contact 2 (day 270). Abbreviations: 30 RSV-PreF/60 RSV-PreF/120 RSV-PreF, group of women who received 1 dose of the unadjuvanted respiratory syncytial virus (RSV) vaccine containing 30, 60, or 120 μg of RSV prefusion F protein; Control, group of women who received 1 dose of placebo; SAE, serious adverse event.

Figure 3.

Geometric mean respiratory syncytial virus–A neutralizing antibody titers (A), geometric mean respiratory syncytial virus–B neutralizing antibody titers (B), and geometric mean palivizumab-competing antibody concentrations (C) until day 90 (per-protocol set). Error bars represent 95% confidence intervals. The raw data for the 60 μg and 120 μg groups are so similar as to be indistinguishable in Figure 3C. Abbreviations: 30 RSV-PreF/60 RSV-PreF/120 RSV-PreF, group of women who received 1 dose of the unadjuvanted RSV vaccine containing 30, 60, or 120 μg of RSV prefusion F protein; CI, confidence interval; Control, group of women who received 1 dose of placebo; GMC, geometric mean concentration; GMT, geometric mean titer; RSV, respiratory syncytial virus.

Figure 4.

Solicited injection site and general adverse events reported within 7 days after vaccination (exposed set). Error bars represent 95% confidence intervals. Abbreviations: 30 RSV-PreF/60 RSV-PreF/120 RSV-PreF, group of women who received 1 dose of the unadjuvanted respiratory syncytial virus (RSV) vaccine containing 30, 60, or 120 μg of RSV prefusion F protein; AEs, adverse events; CI, confidence interval; Control, group of women who received 1 dose of placebo.