Background Vaccines and vaccine boosting have blunted excess morbidity and mortality from SARS-CoV-2 infection suffered by 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 mRNA vaccines to SARS-CoV-2 in a cohort of NHR and healthcare workers (HCW) over 2 years. We used IFN-γ ELIspot and flow cytometry to assess T cell response before, two weeks and 6 months after the initial series and each of two 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 We show that prior SARS-CoV-2 infection and female sex contribute 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 and 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.

中文翻译：

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对疗养院居民接种 SARS-CoV-2 mRNA 疫苗后 T 细胞反应的纵向分析显示生物性别和 SARS-CoV-2 感染史的影响

背景 疫苗和加强疫苗接种已降低了老年疗养院居民 (NHR) 因 SARS-CoV-2 感染而导致的过高发病率和死亡率。然而，重复接种疫苗对基于生物性别和先前感染 NHR 的 T 细胞反应的影响仍有待研究。方法 我们在两年多的时间里检测了一组 NHR 和医护人员 (HCW) 中 T 细胞对 SARS-CoV-2 mRNA 疫苗的反应。我们使用 IFN-γ ELIspot 和流式细胞术来评估初始系列疫苗和两种加强疫苗接种前、两周和 6 个月后的 T 细胞反应。我们利用混合效应模型纵向分析了这些数据，并检查了我们队列的子集，以了解 T 细胞效应功能的其他变化。结果我们发现，既往 SARS-CoV-2 感染和女性性别有助于 NHR 中较高的 T 细胞反应，但 HCW 则不然。当观察不同时间点时，NHR（而非先前感染过的医护人员）的 T 细胞反应明显高于未感染过的受试者。这些反应模式在多次加强疫苗接种中得以维持，表明 NHR 群体的年龄、多发病和/或虚弱可能会加剧 T 细胞对 mRNA 疫苗接种反应的性别和感染状态差异。