Characterizing the Short- and Long-Term Temporal Dynamics of Antibody Responses to Influenza Vaccination

Most influenza vaccine studies evaluate acute antibody responses 1 month post-vaccination, leaving long-term immunity poorly understood. Here, we performed a combined analysis of 14 large-scale vaccine studies and conducted two new studies mapping antibody responses in high resolution from their inception out to 1 year post-vaccination. Vaccine antibody responses were classified as weak (<4x fold-change at 1 month and 1 year), transient (≥4x at 1 month, <4x at 1 year), or durable (≥4x at 1 month and 1 year). Surprisingly, >50% of vaccine recipients were weak across seasons, age groups, sexes, pre-vaccination titers, and high or standard vaccine doses. Peak fold-change at 1 month post-vaccination was strongly associated with the long-term response, with most transient responders achieving a maximum fold-change of 4x, while most durable responders reached ≥16x, with both groups maintaining these titers for 2 months (10-75 days post-vaccination). Using the weak, transient, and durable trajectories, a single time point early in the response (days 7-8 or 21) predicted an individual's response out to 1 year post-vaccination. These results demonstrate that influenza vaccine responses range from little-to-no response to eliciting strong-and-durable immunity, highlighting the stark heterogeneity that is consistently seen across influenza seasons.