Persistence of Antibody to Influenza Hemagglutinin over Two Influenza Seasons
Methods: Healthy subjects ages 18 to 49 years were enrolled in a double-blind trial and randomized to receive inactivated (IIV) or live-attenuated (LAIV) influenza vaccine or placebo. Subjects were followed over two influenza seasons (October 2005 - May 2007) without re-vaccination in the second. Serologic specimens were collected at 5 time points over follow-up. Hemagglutination inhibition (HAI) assays were performed on serologic specimens to determine HAI titers to the influenza A (H3N2) and B strains included in the 2005-06 vaccine. Rates of antibody decline among 941 subjects without evidence of influenza infection were estimated in linear models with mean log2 HAI titer as the outcome and time from intervention as the exposure.
Results: IIV recipients achieved higher mean log2 HAI titers one month post-intervention than LAIV or placebo recipients (P<0.001). IIV recipients also experienced the highest rates of antibody decline; however, this appears to be driven by an association with higher peak antibody levels rather than a specific intervention effect. Despite higher rates of decline, IIV recipients maintained higher titers than LAIV or placebo recipients after 18 months (P<0.001). IIV recipients known to have been vaccinated in the 2004-05 season had higher titers prior to 2005-06 vaccination (P<0.001), but lower titers for the entire post-vaccination period than those not known to have been previously vaccinated (P<0.001).
Conclusion: Moderate HAI titer decreases were observed over 18 months, suggesting a slower rate of decline than previously thought. The rate of decline increases as peak post-vaccination titer increases. Subjects vaccinated two years in a row exhibited decreased vaccine response in the second year. The impact of the persistence of HA antibody, and other immune correlates, on vaccine efficacy requires further study.
J. G. Petrie,
R. Cross, None
A. Monto, Sanofi Pasteur: Consultant and Grant Investigator, Consulting fee and Grant recipient
GSK: Scientific Advisor, Consulting fee