Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Tetanus, Diphtheria, and Acellular Pertussis Vaccine

Abstract

Background: Prevention of respiratory syncytial virus (RSV) disease in infants is an unmet vaccine need, and maternal immunization is a potential strategy to address this need. This study evaluated concomitant administration of RSV stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) in healthy, nonpregnant women 18‒49 years of age.

Methods: In this phase 2b, multicenter, placebo-controlled, observer-blind, noninferiority study, participants were randomized to receive RSVpreF in a range of doses and formulations with Tdap or alone, or Tdap alone. Safety and immunogenicity were assessed.

Results: Local reactions and systemic events were generally similar across vaccine groups. Noninferiority of anti-RSV-A and anti-RSV-B immune responses induced by RSVpreF with Tdap was demonstrated compared to RSVpreF alone. Noninferiority of anti-diphtheria toxoid and anti-tetanus toxoid immune responses after administration of RSVpreF with Tdap was demonstrated compared to Tdap alone; noninferiority was not met for anti-pertussis component responses.

Conclusions: RSVpreF was safe and well tolerated when administered with Tdap or alone in nonpregnant women 18‒49 years of age. Immune responses induced by Tdap administered with RSVpreF were noninferior for the tetanus and diphtheria components of Tdap, but not for pertussis.

Clinical trials registration: NCT04071158.

Keywords: RSV vaccine; Tdap vaccine; immunogenicity; maternal immunization; respiratory syncytial virus; safety.

Figure 1.

Participant disposition. Abbreviations: Al(OH)₃,aluminum hydroxide; f/u,follow-up; RSVpreF,respiratory syncytial virus stabilized prefusion F subunit vaccine; Tdap,tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed.

Figure 2.

Percentages of participants reporting local reactions (A) or systemic events (B) by severity within 7 days after vaccination. Number of participants, 141–143 per vaccine group. Abbreviations: Al(OH)₃,aluminum hydroxide; RSVpreF,respiratory syncytial virus stabilized prefusion F subunit vaccine; Tdap,tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed.

Figure 3.

Noninferiority of respiratory syncytial virus stabilized prefusion F subunit vaccine (RSVpreF) and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (Tdap) coadministration (combination of RSVpreF 120 μg/Tdap and RSVpreF 240 μg + Al(OH)₃/Tdap groups) compared with Tdap alone for anti-tetanus toxoid (TTd) and anti-diphtheria toxoid (DTd) antibodies (A) and anti-pertussis components (B). ^†Difference in the percentage of participants achieving anti-TTd or anti-DTd antibody concentrations ≥0.1 IU/mL between the combined RSVpreF/Tdap groups and placebo/Tdap group (RSVpreF/Tdap – placebo/Tdap). ^‡Geometric mean ratios (GMRs) were calculated as the group mean differences of logarithmically transformed antibody levels and back-transformed to the original units. Anti-pertussis component antibody GMRs were calculated using combined RSVpreF/Tdap GMCs as numerators and placebo/Tdap GMCs as denominators, and RSV neutralizing titer GMRs were calculated using combined RSVpreF/Tdap geometric mean titers (GMTs) as numerators and combined RSVpreF/placebo GMTs as denominators. Noninferiority for anti-pertussis toxin, anti-pertactin, and anti-filamentous hemagglutinin required the lower 95% confidence limit to be >0.67. Noninferiority for RSV-A– and RSV-B– neutralizing titers required the lower 95% confidence limit to be >0.5 for the primary objective and >0.67 for the secondary objective. Abbreviations: CI, confidence interval; DTd,diphtheria toxoid; FHA,filamentous hemagglutinin; GMR,geometric mean ratio; PRN,pertactin; PT,pertussis toxin; TTd,tetanus toxoid; RSV,respiratory syncytial virus.