Combination Flu and COVID-19 Vaccine Prompts Immune Response in Older Adults

A recent study of Moderna’s combination influenze (flu) and COVID-18 vaccine, mRNA-1083, found that it induced higher immune responses than recommended standard care influenza (standard and high dose) and COVID-19 vaccines against all four influenza strains (among those ages 50 to 64 years), the three clinically relevant influenza strains (among those aged 65 years and older), and SARS-CoV-2 (all ages), with an acceptable tolerability and safety profile.

The Phase III, randomized, observer-blinded trial was conducted across 146 U.S. sites in adults 50 years and older enrolled between Oct. 19, 2023, and Nov. 21, 2023. Participants in two age cohorts (65 years and older and 50 to 64 years) were randomly assigned 1:1 to receive mRNA-1083 plus placebo or coadministered licensed quadrivalent seasonal influenza (65 years and older: high-dose quadrivalent inactivated influenza vaccine [HD-IIV4]; 50 to 64 years: standard-dose IIV4 [SD-IIV4]) and COVID-19 (all ages: mRNA-1273) vaccines.

The primary objectives were to demonstrate the noninferiority of humoral immune responses following mRNA-1083 versus comparators against vaccine-matched strains at day 29 and to evaluate the reactogenicity and safety of mRNA-1083. Secondary objectives included demonstration of superiority of humoral immune responses elicited by mRNA-1083 relative to comparators at day 29.

Overall, 8,015 participants were enrolled and vaccinated (4,017 aged 65 yearss and older and 3,998 aged 50 to 64 years). Among adults 65 years and older and 50 to 64 years, the median age was 70 and 58 years, 54.2 percent and 58.8 percent were female, 18.4 percent and 26.7 percent were Black or African American, and 13.9 percent and 19.3 percent were Hispanic or Latino, respectively. Noninferior immunogenicity of mRNA-1083 was demonstrated against all vaccine-matched influenza and SARS-CoV-2 strains based on lower bound of the 97.5 percent confidence interval (CI) of the geometric mean ratio greater than 0.667 and lower bound of the 97.5 percent CI of the seroconversion/seroresponse rate difference greater than minus 10 percent. mRNA-1083 elicited higher immune responses than SD-IIV4 (50 to 64 years) for all four influenza strains and HD-IIV4 (65 years and older) for three influenza strains (A/H1N1, A/H3N2, B/Victoria) and against SARS-CoV-2 (all ages). Solicited adverse reactions were numerically higher in frequency and severity after mRNA-1083 vaccination than comparators in both age cohorts (65 years and older: 83.5 percent and 78.1 percent; 50 to 64 years: 85.2 percent and 81.8 percent); most were grade 1 or 2 in severity and of short duration. No safety concerns were identified.