Immunogenicity and safety of AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8)-like influenza vaccine in adults: Phase 1/2, observer-blinded, randomized trial

Clinical Snapshot

Key Findings

• P Value: Not reported in available abstract

• Effect Size: Higher immune responses with AS03A vs AS03B, younger vs older adults

• Primary Outcome: Met FDA CBER criteria for influenza vaccines on day 43 post-vaccination

• Nnt Or Sensitivity: Demonstrated antigen-sparing potential of AS03 adjuvant system

• Confidence Interval: Not reported in available abstract

Clinical Application

Intramuscular administration, standard two-dose schedule feasible in clinical practice Relevant for Australian pandemic preparedness planning; TGA would need to evaluate for local approval; could complement existing influenza vaccination programs Healthy adults aged 18+ years requiring pandemic influenza vaccination

Abstract

Influenza pandemics arise from novel influenza A viruses. Recent emergence of a new clade (2.3.4.4.b) of the highly pathogenic H5N1 in animals and humans highlighted its pandemic potential. We evaluated the immunogenicity and safety of GSK's AS03-adjuvanted H5N8 vaccine in adults. In this phase 1/2, observer-blinded, age-stratified, randomized trial, healthy US adults (age, ≥18 y) received two intramuscular doses of hemagglutinin antigen (3.75 or 7.50 μg) with AS03A or AS03B, administered 21 d apart. Immunogenicity - seroprotection rates (SPRs), seropositivity, geometric mean titers (GMTs), geometric mean fold rise (GMFR), and seroconversion rates (SCRs) - was evaluated on day 43 using hemagglutination inhibition (HI) and microneutralization (MN) assays. Safety was monitored throughout the study. Of 520 enrolled participants, 518 were vaccinated. On day 43, the US Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research criteria for influenza vaccines were met. HI SPRs, seropositivity rates, SCRs, GMTs, and GMFR appeared to be higher in the AS03A vs AS03B group. Immune responses were generally higher in younger (aged 18-64 y) vs older (aged ≥65 y) adults. Immune responses were also detected in MN assays, with a correlation between HI and MN responses on day 43 across age groups and vaccine formulations. Safety was acceptable, with no increase in adverse events post-dose 2. Reactogenicity appeared more common in younger adults. The antigen-sparing potential of AS03 was demonstrated, with an acceptable safety profile. The benefit/risk profile was favorable for all formulations tested, including 3.75 µg AS03A (licensed in the US).ClinicalTrials.gov registration: NCT05975840. Influenza pandemics occur when new influenza viruses emerge, causing widespread illness. A recent study investigated a new vaccine, GSK’s AS03-adjuvanted H5N8 influenza vaccine, for its ability to trigger an immune response and its safety in adults aged 18–64 y and older adults aged ≥65 y. Overall, 518 participants received at least one dose of the vaccine, with different amounts of hemagglutinin antigen (3.75 or 7.50 µg) combined with different concentrations of AS03 adjuvant. Immune responses were assessed at multiple time points, with the primary endpoint measured on day 43 post-vaccination. The vaccine produced a strong immune response in both age groups, with younger adults showing slightly better responses than older adults. The vaccine met the required standards for an immune response set by the US Food and Drug Administration (FDA). AS03A typically induced greater immune response than AS03B. Safety monitoring showed that the vaccine was generally well tolerated, with the most common side effects being mild, such as injection-site pain and muscle ache. This study confirmed that the AS03-adjuvanted H5N8 vaccine has the potential to provide protection against influenza with an acceptable safety profile, making it a valuable candidate for pandemic preparedness.

References

1. 1.Hastie, A., Gupta, V., Lese, P., Moya, J., Schoonbroodt, S., Beudjekian, S., & Struyf, F. (2026). Immunogenicity and safety of AS03-adjuvanted A/Astrakhan/3212/2020 (H5N8)-like influenza vaccine in adults: Phase 1/2, observer-blinded, randomized trial. Human Vaccines & Immunotherapeutics. https://doi.org/10.1080/21645515.2026.2649314