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Sex-specific effects of aging on the humoral immune response to repeat vaccination with the high-dose seasonal influenza vaccine in older adults

By Janna Shapiro, Huifen Li, Rosemary Morgan, Yiyin Chen, Helen Kuo, Xiaoxuan Ning, Patrick Shea, Cunjin Wu, Katherine Merport, Rayna Saldanha, Suifeng Liu, Engle Abrams, Yan Chen, Denise C. Kelly, Eileen Sheridan-Malone, Lan Wang, Scott L Zeger, Sabra L. Klein, Sean X. Leng

Posted 23 Jul 2021
medRxiv DOI: 10.1101/2021.07.21.21260712

Older adults ([≥]65 years of age) bear a significant burden of severe disease and mortality associated with influenza, despite relatively high annual vaccination coverage and substantial pre-existing immunity to influenza. To test the hypothesis that host factors, including age and sex, play a role in determining the effect of repeat vaccination and levels of pre-existing humoral immunity to influenza, we evaluated pre- and post-vaccination strain-specific hemagglutination inhibition (HAI) titers in adults over 75 years of age who received a high-dose influenza vaccine in at least four out of six influenza seasons (NCT02200276). Neither age, sex, body mass index, frailty, nor repeat vaccination were significantly associated with post-vaccination HAI titer outcomes. Pre-vaccination titers, however, were significantly predictive of post-vaccination outcomes. Pre-vaccination titers to H1N1 remained constant with age, while those to H3N2 and influenza B decreased substantially with age in males but not in females. Our findings highlight the importance of pre-existing immunity in this highly vaccinated older adult population and suggest that older males are particularly vulnerable to reduced pre-existing humoral immunity to influenza from previous annual vaccination.

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