Written By: Pharmacally Medical News Desk
Pfizer has announced positive results from its Phase 3 trial of a quadrivalent nucleoside-modified mRNA (modRNA) influenza vaccine, showing 34.5% greater efficacy than a standard licensed flu vaccine in preventing influenza-like illness among adults aged 18 to 64 during the 2022–2023 flu season. The data were published recently in the New England Journal of Medicine, representing a major milestone for mRNA technology in seasonal influenza prevention.
Study Design and Endpoints
The randomized, controlled, double-blind phase 3 trial (NCT05540522) enrolled 18,476 participants from the United States, South Africa, and the Philippines. Participants received either 30 µg of the quadrivalent modRNA influenza vaccine or a standard licensed inactivated vaccine. The primary endpoint of the Pfizer Phase 3 modRNA influenza vaccine trial was to measure the relative vaccine efficacy, defined as the reduction in laboratory-confirmed influenza-like illness occurring at least 14 days after vaccination.
Secondary endpoints included detailed assessments of immunogenicity through hemagglutination inhibition (HAI) assay titers, which quantify antibody responses, and evaluations of T-cell mediated immunity. Safety was comprehensively monitored by documenting reactogenicity symptoms within the first 7 days post-vaccination, tracking adverse events for up to 1 month, and following serious adverse events over a longer period of 6 months. This robust design ensured thorough evaluation of both the protective efficacy and the safety profile of the vaccine.
Results
Efficacy: The modRNA vaccine achieved 34.5% relative efficacy with 57 influenza cases in the modRNA group vs. 87 in the control group. Efficacy was consistent in the modified intention-to-treat population and at end-of-season analysis.
Immunogenicity: Higher HAI antibody titers against influenza A strains with confirmed noninferiority and higher seroconversion rates were observed in the modRNA group. The response to influenza B strains did not meet noninferiority criteria, likely due to low B strain circulation during the trial.
Cellular immunity: The modRNA vaccine elicited stronger CD4+ and CD8+ T-cell interferon-γ responses sustained up to 6 months post-vaccination.
Safety: Reactogenicity was more frequent in the modRNA group (70.1% local reactions, 65.8% systemic events) but mostly mild to moderate and transient. Fever occurred in 5.6% vs. 1.7% in control recipients. Serious adverse events, severe events, and withdrawals were low and similar across groups, with no increased risk of myocarditis or pericarditis.
Safety Profile
The modRNA vaccine’s safety profile mirrors that of other mRNA vaccines: higher rates of injection site pain, fatigue, headache, and fever compared to traditional vaccines, but these reactions were generally short-lived and well-tolerated. Only one vaccine-related serious adverse event was reported (grade 3 injection site reaction and grade 4 anaphylaxis). No clinically significant safety concerns emerged over 6 months of follow-up.
Public Health Implications and Advantages over Standard Vaccine
Pfizer’s modRNA influenza vaccine offers several advantages:
Improved efficacy and immune response: Superior protection primarily against flu A strains, with heightened antibody and T-cell responses potentially translating to more durable and broader immunity.
Manufacturing benefits: Faster, scalable production without egg-based limitations or risks of egg-adapted mutations that can reduce effectiveness in traditional vaccines.
Flexibility: The modRNA platform allows rapid updates to vaccine strains in response to evolving viruses, a key advantage for seasonal influenza.
Safety: The safety profile is consistent with mRNA vaccines and acceptable for widespread use.
These findings suggest that transitioning to mRNA-based influenza vaccines could substantially reduce flu illness burden, especially among adults under 65. However, further research is needed for vaccine efficacy in older adults, protection against influenza B, and across multiple seasons.
References
D Fitz-Patrick et al, Efficacy, Immunogenicity and Safety of Modified MRNA Influenza Vaccine, The New Eng J Medicine, N Engl J Med, 2025 Nov 20;393(20):2001-2011, doi: 10.1056/NEJMoa2416779.
A Study to Evaluate a Modified RNA Vaccine against Influenza in Adults 18 Years of Age or Older, ClinicalTrials.gov ID NCT05540522, https://clinicaltrials.gov/study/NCT05540522