More Shots on Goal: Heterologous Influenza Prime-Boost Vaccination Decreases the Likelihood of a Negligible Antibody Response to Current or Historical Variants

A heterologous influenza prime-boost in a phase 4 trial reduced non-responders with HAI≤10 across all time points, including 0% H3N2 non-responders after prime and boost.

• Why it matters: Seasonal influenza shots often leave a subset with negligible, non-durable antibody responses, and prior homologous boosting has not reliably improved magnitude or breadth.
• What they did: Participants received a late-season 2023 inactivated influenza vaccine followed four months later by a 2024 booster with an updated H3N2 plus unchanged H1N1 and B/Victoria, enabling within-subject comparison of heterologous versus homologous boosting.
• The result: The booster halted or reversed titer waning for all strains and lowered non-response rates, with a similar pattern in a larger consecutive-fall cohort (20% H3N2 vs 37% H1N1), implying multi-strain exposure can reduce the non-responder fraction.

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