Single mRNA Shot Matches or Beats Separate Flu and COVID Vaccines in Adults 50+
A phase 3 trial finds Moderna's combo flu+COVID mRNA vaccine mRNA-1083 is at least as effective—and often superior—to standard separate vaccines.
Summary
A phase 3 randomized trial of 8,015 adults aged 50 and older tested mRNA-1083, Moderna's investigational combination mRNA vaccine targeting both seasonal influenza (all four strains) and SARS-CoV-2 (Omicron XBB.1.5). Participants received either mRNA-1083 plus placebo or standard-care coadministered influenza and COVID-19 vaccines. mRNA-1083 met all noninferiority criteria and surpassed comparators: it outperformed standard-dose flu vaccine across all four strains (ages 50–64), high-dose flu vaccine on three of four strains (ages 65+), and bested mRNA-1273 for SARS-CoV-2 responses in both age groups. Solicited adverse reactions were slightly more frequent with mRNA-1083 but were mostly mild-to-moderate and short-lived. No new safety signals emerged.
Detailed Summary
Annual uptake of both influenza and COVID-19 vaccines remains well below public health targets, partly due to the burden of receiving multiple injections. A single combination vaccine could streamline immunization and potentially improve compliance—particularly in older adults, who face elevated risk from both respiratory illnesses.
This phase 3, randomized, observer-blinded trial (NCT06097273) enrolled 8,015 adults across 146 US sites between October and November 2023. Participants were stratified into two age cohorts (≥65 years, n=4,017; 50–64 years, n=3,998) and randomized 1:1 to receive either mRNA-1083 (plus placebo injection) or age-appropriate licensed comparators: high-dose quadrivalent inactivated influenza vaccine (HD-IIV4) plus mRNA-1273 for those ≥65, and standard-dose IIV4 (SD-IIV4) plus mRNA-1273 for those 50–64. The primary endpoints were noninferiority of hemagglutination inhibition (HAI) titers for influenza strains and pseudovirus neutralization titers for SARS-CoV-2 at day 29, with secondary endpoints testing superiority.
mRNA-1083 achieved noninferiority against all four vaccine-matched influenza strains (A/H1N1, A/H3N2, B/Victoria, B/Yamagata) and against SARS-CoV-2, in both age cohorts. Superiority was also demonstrated: among 50–64-year-olds, mRNA-1083 elicited significantly higher immune responses than SD-IIV4 for all four influenza strains. Among adults ≥65, it outperformed HD-IIV4 on three of four strains (A/H1N1, A/H3N2, B/Victoria) but not B/Yamagata. For COVID-19, mRNA-1083 produced superior SARS-CoV-2 neutralizing antibody responses compared with mRNA-1273 in both age groups.
Solicited adverse reactions were modestly more common with mRNA-1083 (83.5% vs 78.1% in ≥65 cohort; 85.2% vs 81.8% in 50–64 cohort), but the vast majority were grade 1 or 2 and resolved quickly. No serious safety concerns attributable to mRNA-1083 were identified. The demographic composition—including meaningful representation of Black/African American (18–27%) and Hispanic/Latino (14–19%) participants—strengthens generalizability.
These results suggest mRNA-1083 could serve as a simplified, single-injection annual immunization option for older adults, potentially reducing the logistical and psychological barriers that suppress dual-vaccine uptake. Pending regulatory review, this multicomponent mRNA vaccine represents a meaningful advance in adult vaccine convenience and immunogenicity.
Key Findings
- mRNA-1083 met noninferiority criteria vs comparators for all 4 influenza strains and SARS-CoV-2 in both age groups.
- In adults 50–64, mRNA-1083 surpassed standard-dose flu vaccine on all 4 influenza strains.
- In adults ≥65, mRNA-1083 outperformed high-dose flu vaccine on 3 of 4 strains (A/H1N1, A/H3N2, B/Victoria).
- mRNA-1083 generated superior COVID-19 neutralizing antibody responses vs mRNA-1273 across all ages.
- Adverse reactions were slightly more frequent with mRNA-1083 but mostly mild/moderate with no new safety signals.
Methodology
Phase 3, randomized, observer-blinded trial across 146 US sites enrolling 8,015 adults ≥50 years, stratified by age cohort (50–64 and ≥65). Participants were randomized 1:1 to mRNA-1083 plus placebo or age-appropriate licensed influenza vaccine plus mRNA-1273, with primary immunogenicity endpoints assessed at day 29 using HAI titers (influenza) and pseudovirus neutralization titers (SARS-CoV-2).
Study Limitations
The trial measured antibody responses as immunogenicity surrogates rather than directly demonstrating reduction in clinical influenza or COVID-19 illness. The 29-day immunogenicity window does not address durability of protection. As a Moderna-funded and -conducted study, independent replication and regulatory scrutiny will be important before clinical adoption.
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