Combo flu, COVID-19 vaccine noninferior in adults ages 50 years and older, manufacturer trial finds

An mRNA vaccine against both seasonal influenza and COVID-19 was at least as immunogenic as recommended standard vaccines and well tolerated in adults ages 50 years and older, a phase 3 study found.

To assess a multicomponent vaccine against seasonal influenza and SARS-CoV-2 (mRNA-1083), researchers conducted a phase 3 randomized observer-blinded study at 146 sites. Participants in two age cohorts were randomly assigned to the vaccine candidate or licensed seasonal influenza vaccine (A/H1N1, A/H3N2, B/Victoria, B/Yamagata) coadministered with licensed SARS-CoV-2 (Omicron XBB.1.5) vaccine. Those ages 65 years and older got a high-dose quadrivalent inactivated influenza vaccine while those ages 50 to 64 years got a standard-dose flu shot.

The study was funded by Moderna and designed 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. Results were published online May 7 by JAMA.

There were 8,015 participants (4,017 ages ≥65 years and 3,998 ages 50 to 64 years). Noninferior immunogenicity of mRNA-1083 was demonstrated against all vaccine-matched influenza and SARS-CoV-2 strains. The mRNA-1083 vaccine elicited higher immune responses versus the standard-dose vaccine for all four influenza strains and versus the high-dose flu vaccine for three influenza strains (A/H1N1, A/H3N2, B/Victoria), as well as against SARS-CoV-2. Adverse reactions were more common after mRNA-1083 vaccination than comparators in both age cohorts (83.5% vs. 78.1% for ages ≥65 years and 85.2% vs. 81.8% for ages 50 to 64 years), but most were short-lived and grade 1 or 2 in severity.

Researchers stated that the mRNA platform has numerous advantages, including avoidance of egg adaptation-related changes and broader immunity and T-cell responses for the influenza component. In addition, they said, it offers rapid production and flexibility for updates to vaccine composition that can ensure close matching to circulating virus strains. An annual campaign with a multicomponent vaccine could occur when the burden of respiratory hospitalizations is the greatest, while allowing for a stand-alone COVID-19 vaccine option for additional doses or an updated vaccine if an antigenically divergent strain emerges in the interim, the authors wrote.

“In addition, a multicomponent vaccine against influenza and COVID-19 has potential to improve coverage and increase compliance with recommendations, therefore reducing COVID-19-related and influenza-related outcomes and health care system burden in adults 50 years and older,” they wrote.