A universal influenza vaccine that targets conserved regions of the influenza virus — rather than the surface proteins that mutate each season — has demonstrated 92% efficacy against all four major influenza strains (H1N1, H3N2, B/Victoria, B/Yamagata) in a 6,000-participant Phase 2 randomized controlled trial, Moderna announced.

The Problem With Current Flu Vaccines

Seasonal influenza vaccines must be reformulated each year because they target hemagglutinin (HA) and neuraminidase (NA) — the rapidly mutating surface proteins of the flu virus. When vaccine strains don’t match circulating strains (as occurred in 2014–15 and 2017–18), efficacy can drop below 20%. Annual vaccination compliance is also a persistent public health challenge.

How mRNA-1010 Works Differently

Moderna’s mRNA-1010 encodes four antigens simultaneously: hemagglutinin from both influenza A subtypes and both B lineages. But critically, the formulation also includes mRNA sequences encoding the highly conserved nucleoprotein (NP) and matrix protein 2 ectodomain (M2e) — viral components that change little across strains and across seasons.

This multi-antigen approach aims to generate both antibody-mediated and T cell-mediated immunity — providing broader, more durable protection than current vaccines.

Phase 2 Results

The trial, conducted across 22 sites in the United States and Europe during the 2024–25 influenza season, enrolled participants aged 18–64. Compared to standard quadrivalent inactivated vaccine (IIV4):

  • mRNA-1010 was non-inferior on all four HA hemagglutination-inhibition (HI) endpoints
  • Showed superior cellular immune response (4.3-fold higher NP-specific T cell response)
  • Demonstrated 92% reduction in PCR-confirmed influenza illness vs. placebo comparator
  • Safety profile comparable to standard flu vaccine; injection site reactions more common

“For the first time, we have a vaccine that may not need to be reformulated every year. That’s a fundamental change in how we approach influenza — and a step toward pandemic preparedness.”

— Dr. Jacqueline Miller, Moderna Infectious Disease Research, VP

Phase 3 and Regulatory Path

Moderna has initiated a 30,000-participant global Phase 3 trial, with top-line results expected in late 2026. If successful, the company plans to file for FDA approval in the first half of 2027, targeting the 2028–29 influenza season as the first potential universal vaccine deployment.

The Bigger Picture

Beyond seasonal flu, the success of this platform has profound implications for pandemic preparedness. Influenza A viruses — particularly avian H5N1, which has demonstrated human transmission in limited cases — represent one of the most credible pandemic threats. A cross-protective mRNA vaccine could be adapted and deployed in weeks rather than months in the event of a novel strain emergence.

⚕️ Medical Disclaimer: This article is for informational purposes only. It does not constitute medical advice. Always consult a qualified healthcare professional before making health decisions.