Long‐term dynamics of natural killer cells in response to SARS‐CoV‐2 vaccination: Persistently enhanced activity postvaccination

Abstract

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.