Longitudinal Analysis of Nursing Home Residents' T-Cell Responses After SARS-CoV-2 mRNA Vaccinations Shows Influence of Biological Sex and Infection History.

Background: Vaccines and vaccine boosting have blunted excess morbidity and mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in older nursing home residents (NHR). However, the impact of repeated vaccination on the T-cell response based on biological sex and prior infection of NHR remain understudied.
Methods: We examined T-cell responses to SARS-CoV-2 mRNA vaccines in a cohort of NHR and healthcare workers (HCW) over 2 years. We used interferon-γ ELIspot and flow cytometry to assess T-cell response before, 2 weeks, and 6 months after the initial series and each of 2 booster vaccines. We analyzed these data longitudinally with mixed-effect modeling and also examined subsets of our cohorts for additional changes in T-cell effector function.
Results: Prior SARS-CoV-2 infection and female sex contributed to higher T-cell response in NHR but not HCW. When looking across time points, NHR but not HCW with prior infection had significantly higher T-cell responses than infection-naive subjects. These patterns of response were maintained across multiple booster vaccinations.
Conclusions: These results suggest that the age, multimorbidity, and/or frailty of the NHR cohort may accentuate sex and infection status differences in T-cell response to mRNA vaccination.
Competing Interests: Potential conflicts of interest. S. G. and D. H. C. are recipients of investigator-initiated grants to their universities from Pfizer to study pneumococcal vaccines, Sanofi Pasteur and Seqirus to study influenza vaccines, and Moderna to study respiratory infection. S. G. is recipient of investigator-initiated grant to the university from Genentech on influenza antivirals; reports consulting for Seqirus, Sanofi, Merck, Vaxart, Novavax, Moderna, and Janssen; has served on the speaker bureaus for Seqirus and Sanofi; reports personal fees from Pfizer; and reports data and safety monitoring board fees from Longevoron and SciClone. C. S. is now employed by CSL Seqirus. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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