Natural Killer (NK) cells play a significant role in the early defense against virus infections and cancer. Recent studies have demonstrated the involvement of NK cells in both the induction and effector phases of vaccine‐induced immunity in various contexts. However, their role in shaping immune responses following SARS‐CoV‐2 vaccination remains poorly understood. To address this matter, we conducted a comprehensive analysis of NK cell phenotype and function in SARS‐CoV‐2 unexposed individuals who received the BNT162b2 vaccine. We employed a longitudinal study design and utilized a panel of 53 15‐mer overlapping peptides covering the receptor binding domain (RBD) of the SARS‐CoV‐2 Spike protein to assess NK cell function at 0 and 20 days following the first vaccine, and 30 and 240 days following booster. Additionally, we evaluated the levels of total IgG anti‐Spike antibodies and their potential neutralizing ability. Our findings revealed an increased NK cell activity upon re‐exposure to RBD when combined with IL12 and IL18 several months after booster. Concurrently, we observed that the frequencies of NKG2A + NK cells declined over the course of the follow‐up period, while NKG2C increased only in CMV positive subjects. The finding that NK cell functions are inducible 9 months after vaccination upon re‐exposure to RBD and cytokines, sheds light on the role of NK cells in contributing to SARS‐CoV‐2 vaccine‐induced immune protection and pave the way to further studies in the field.

中文翻译：

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自然杀伤细胞响应 SARS-CoV-2 疫苗接种的长期动态：疫苗接种后活性持续增强

自然杀伤 (NK) 细胞在病毒感染和癌症的早期防御中发挥着重要作用。最近的研究表明，NK 细胞在各种情况下参与疫苗诱导免疫的诱导期和效应期。然而，它们在 SARS-CoV-2 疫苗接种后形成免疫反应中的作用仍知之甚少。为了解决这个问题，我们对接受 BNT162b2 疫苗的 SARS-CoV-2 未暴露个体的 NK 细胞表型和功能进行了全面分析。我们采用纵向研究设计，并利用一组覆盖 SARS-CoV-2 刺突蛋白受体结合域 (RBD) 的 53 个 15 聚体重叠肽来评估首次接种疫苗后 0 和 20 天的 NK 细胞功能，并且加强剂后 30 和 240 天。此外，我们评估了总 IgG 抗 Spike 抗体的水平及其潜在的中和能力。我们的研究结果表明，在加强免疫几个月后，与 IL12 和 IL18 联合使用 RBD 后，NK 细胞活性增加。同时，我们观察到 NKG2A + NK 细胞的频率在随访期间下降，而 NKG2C 仅在 CMV 阳性受试者中增加。接种疫苗后 9 个月，再次暴露于 RBD 和细胞因子时，NK 细胞功能可被诱导，这一发现揭示了 NK 细胞在 SARS-CoV-2 疫苗诱导的免疫保护中的作用，并为进一步研究铺平了道路。场。