Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults over 75 years of age

This is the authors' abstract. We don't add key points for this paper.

Background: Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI antibody titer is a valuable indicator of pre-existing humoral immunity at the beginning of the influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason decline has been challenging. This is because pre-vaccination HAI antibody titers are conventionally measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized, and do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI antibody titers measured using prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017 during which influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains were changed in 2015 and in 2016. While the IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, it was changed in the 2017 season. Finally, we investigated factors contributing to pre-existing humoral immunity. Results: Interseason decline of HAI antibody titers was evident, but rates of decline varied among vaccine strains and study seasons, from 18% (p=0.43) to 61% (p<0.01). Rates of decline were noticeably greater when pre-vaccination HAI titers were measured using the conventional approach, from 33% (p=0.12) to 83% (p<0.01). All p values were adjusted for age at prior study season, sex, race, and education. This was largely because the conventional approach underestimated residual HAI antibody titers from prior season vaccinations. Moreover, interseason antibody decline and prior season post-vaccination HAI antibody titer had significant and independent associations with pre-vaccination HAI antibody titer. Conclusions: The conventional approach overestimates interseason HAI antibody decline as it underestimates residual antibody titers from prior season vaccination, particularly when virus strains in the vaccine formula change. Moreover, interseason antibody decline and prior season post-vaccination HAI antibody titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.