A recent phase III trial evaluated the safety and immunogenicity of the mRNA-1345 respiratory syncytial virus vaccine when coadministered with either a standard-dose quadrivalent inactivated influenza vaccine or a bivalent COVID-19 vaccine (mRNA-1273.214) in adults aged 50 years and older.
In the randomized, observer-blinded, placebo-controlled trial, published in The Lancet Infectious Diseases, researchers recruited 3,314 participants across two parts.
The coadministered vaccine regimens demonstrated acceptable safety profiles. As of the 6-month (part A) and 7-month (part B) follow-up periods, no serious adverse events, adverse events of special interest, study discontinuations caused by adverse events, or fatal events considered related to study vaccination were reported.
Lead study author Jaya Goswami, MD, stated: “Coadministered mRNA-1345 plus standard-dose quadrivalent inactivated influenza vaccine or mRNA-1273.214 vaccine had acceptable safety profiles and elicited mostly noninferior immune responses compared to individual vaccines in adults aged 50 years or older.”
In part A of the study, 1,631 participants were randomly assigned in a 7:10:10 ratio to receive mRNA-1345 plus standard-dose quadrivalent inactivated influenza vaccine, mRNA-1345 plus placebo, or standard-dose quadrivalent inactivated influenza vaccine plus placebo. The geometric mean ratio of neutralizing antibodies against respiratory syncytial virus (RSV) subtype A for mRNA-1345 plus influenza vaccine vs mRNA-1345 alone was 0.81. However, the seroresponse rate difference didn't meet the prespecified noninferiority margin, with a difference of −11.2%.
In part B, 1,691 participants were randomly assigned in a 1:1:1 ratio to receive mRNA-1345 plus mRNA-1273.214, mRNA-1345 plus placebo, or mRNA-1273.214 plus placebo. The geometric mean ratio of neutralizing antibodies against RSV subtype A for mRNA-1345 plus mRNA-1273.214 vs mRNA-1345 alone was 0.80, and the seroresponse rate difference was −4.4%, which met the noninferiority criterion.
The researchers also evaluated immune responses to the four influenza strains included in the standard-dose quadrivalent inactivated influenza vaccine in part A. Geometric mean ratios for antihemagglutination inhibition antibody titers for mRNA-1345 plus influenza vaccine vs influenza vaccine alone were: 0.89 for A/H1N1, 0.97 for A/H3N2, 0.93 for B/Victoria, and 0.91 for B/Yamagata. All four endpoints met the noninferiority criterion.
The researchers included a diverse population: 54% of participants in part A and 55% in part B were female; the mean age was 63.8 years in part A and 62.5 years in part B. In both parts, 75% to 77% of participants identified as White. Across the full cohort, 18% had preexisting respiratory diseases, 21% had type 2 diabetes, and 10% had cardiac conditions.
The researchers concluded that coadministration of mRNA-1345 with standard-dose quadrivalent inactivated influenza vaccine or mRNA-1273.214 was well tolerated and generally noninferior in terms of immune response, with further evaluation planned to assess long-term safety and effectiveness.
Full disclosures and detailed safety and immunogenicity data are available in the published report.
