Sex-specific effects of aging on humoral immune responses to repeated influenza vaccination in older adults

Janna R. 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

Research output: Contribution to journalArticlepeer-review


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 repeated 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. Pre-vaccination titers, rather than host factors and repeated vaccination were significantly associated with post-vaccination HAI titer outcomes, and displayed an age-by-sex interaction. Pre-vaccination titers to H1N1 remained constant with age. Titers to H3N2 and influenza B viruses decreased substantially with age in males, whereas titers in females remained constant with age. 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.

Original languageEnglish (US)
Article number147
Journalnpj Vaccines
Issue number1
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Infectious Diseases
  • Pharmacology (medical)


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