Abstract
Background: Sex differences in immune responses to influenza vaccine may impact efficacy across populations.Methods: In a cohort of 138 older adults (50–74 years old), we measured influenza A/H1N1 antibody titers, B-cell ELISPOT response, PBMC transcriptomics, and PBMC cell compositions at 0, 3, and 28 days post-immunization with the 2010/11 seasonal inactivated influenza vaccine.Results: We identified higher B-cell ELISPOT responses in females than males. Potential mechanisms for sex effects were identified in four gene clusters related to T, NK, and B cells. Mediation analysis indicated that sex-dependent expression in T and NK cell genes can be partially attributed to higher CD4+ T cell and lower NK cell fractions in females. We identified strong sex effects in 135 B cell genes whose expression correlates with ELISPOT measures, and found that cell subset differences did not explain the effect of sex on these genes' expression. Post-vaccination expression of these genes, however, mediated 41% of the sex effect on ELISPOT responses.Conclusions: These results improve our understanding of sexual dimorphism in immunity and influenza vaccine response.
Highlights
Since 2010, seasonal influenza A is believed to have killed between 12,000 and 79,000 people, has resulted in 140,000–960,000 excess hospitalizations annually in the United States [1], and incurs annual costs of nearly $90 billion [2]
We found that total B cell fractions did not differ significantly between men and women; the numbers of influenzaspecific B cells after vaccination as measured by ELISPOT were significantly higher in women than men
These results suggest that sex differences do not originate in differences in total numbers of B cells, but in a heightened ability of women to respond to vaccination and generate long-lasting influenzareactive memory B cells
Summary
Since 2010, seasonal influenza A is believed to have killed between 12,000 and 79,000 people, has resulted in 140,000–960,000 excess hospitalizations annually in the United States [1], and incurs annual costs of nearly $90 billion [2]. During the 2017–2018 influenza season, seasonal influenza caused nearly 80,000 deaths in the United States alone [3]. As seasonal influenza vaccine efficacy is sub-optimal, and variable in the older adults most likely to be seriously affected by disease [21,22,23,24,25,26,27], sex-based differences in vaccine response further enhance inter-individual differences in influenza protection across populations and exacerbate this major public health issue. Sex differences in immune responses to influenza vaccine may impact efficacy across populations
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