Safety and Immunogenicity of 3 Formulations of an Investigational Respiratory Syncytial Virus Vaccine in Nonpregnant Women: Results From 2 Phase 2 Trials

Jiri Beran, Jason D Lickliter, Tino F Schwarz, Casey Johnson, Laurence Chu, Joseph B Domachowske, Pierre Van Damme, Kanchanamala Withanage, Laurence A Fissette, Marie-Pierre David, Koen Maleux, Alexander C Schmidt, Marta Picciolato, Ilse Dieussaert, Jiri Beran, Jason D Lickliter, Tino F Schwarz, Casey Johnson, Laurence Chu, Joseph B Domachowske, Pierre Van Damme, Kanchanamala Withanage, Laurence A Fissette, Marie-Pierre David, Koen Maleux, Alexander C Schmidt, Marta Picciolato, Ilse Dieussaert

Abstract

Background: Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost preexisting neutralizing antibody titers, providing passive protection to newborns.

Methods: Two observer-blinded, controlled studies (RSV F-020 [clinical trials registration NCT02360475] and RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, nonpregnant 18-45-year-old women. Both studies used a licensed adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis (Tdap) vaccine as a control. RSV F-020 evaluated immunogenicity and safety: participants were randomized (1:1:1:1) to receive 1 dose of RSV-prefusion F protein (PreF) vaccine containing 30 µg or 60 µg of nonadjuvanted RSV-PreF, 60 µg of aluminum-adjuvanted RSV-PreF, or Tdap. RSV F-024 evaluated safety: participants were randomized 1:1 to receive 1 dose of 60 µg of nonadjuvanted RSV-PreF or Tdap.

Results: Both studies showed similar reactogenicity profiles for RSV-PreF and Tdap. No serious adverse events were considered vaccine related. In RSV F-020, geometric mean ratios of RSV-A neutralizing antibody levels at day 30 versus prevaccination were 3.1-3.9 in RSV-PreF recipients and 0.9 in controls. Palivizumab-competing antibody concentrations increased >14-fold in RSV-PreF recipients on day 30. RSV antibody titers waned after day 30 but remained well above baseline through day 90.

Conclusions: All formulations of RSV-PreF boosted preexisting immune responses in 18-45-year old women with comparable immunogenicity. The RSV-PreF safety profile was similar to that of Tdap vaccine.

Figures

Figure 1.
Figure 1.
Study design and procedures. PreF, prefusion protein; RSV, respiratory syncytial virus.
Figure 2.
Figure 2.
Study flow. The 30RSV-PreF group received nonadjuvanted RSV vaccine containing 30 µg of RSV–prefusion F protein (PreF), the 60RSV-PreF group received nonadjuvanted RSV vaccine containing 60 µg of RSV PreF, the 60RSV-PreF-Al group received aluminum-adjuvanted RSV vaccine containing 60 µg of RSV PreF, and the Tdap group received an adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis vaccine. ATP, according to protocol.
Figure 3.
Figure 3.
Solicited injection site and general symptoms reported within 7 days (day 0–6) after vaccination in RSV F-020 and F-024. The 30RSV-PreF group received nonadjuvanted RSV vaccine containing 30 µg of RSV–prefusion F protein (PreF), the 60RSV-PreF groups received nonadjuvanted RSV vaccine containing 60 µg of RSV PreF, the 60RSV-PreF-Al group received aluminum-adjuvanted RSV vaccine containing 60 µg of RSV PreF, and the Tdap groups received an adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis vaccine.
Figure 4.
Figure 4.
(A) Geometric mean anti–respiratory syncytial virus subtype A (RSV-A) neutralizing antibody titers and (B) geometric mean palivizumab-competing antibody concentrations with 95% confidence intervals until day 90 after vaccination—RSV F-020, according-to-protocol immunogenicity cohort. The 30RSV-PreF group received nonadjuvanted RSV vaccine containing 30 µg of RSV–prefusion F protein (PreF), the 60RSV-PreF group received nonadjuvanted RSV vaccine containing 60 µg of RSV PreF, the 60RSV-PreF-Al group received aluminum-adjuvanted RSV vaccine containing 60 µg of RSV PreF, and the Tdap group received an adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis vaccine. LLD, lower limit of detection.

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