Publication date: May 30, 2025

The adaptive immune protection elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has been proven to control the severity of novel coronavirus disease 2019 (COVID-19). However, the contributions of innate lymphoid cells formed from immunization are poorly defined in vaccine evaluation. Here, we highlight how the natural-killer (NK) and macrophage (Mϕ) cells’ response, primed by the inactivated COVID-19 vaccine, is crucial to preventing lung injury. We propose that a specific subset of NK cells, marked CD56CD16NKG2C, along with M2-like Mϕ, CD8 T cells, are important in defending against SARS-CoV-2. Our studies using a rhesus-macaque (RM) model showed that this orchestration of protection was depicted as a trajectory of adaptive NK and Mϕ cell responses from circulating peripheral blood mononuclear cells (PBMCs) to the lungs. Through single-cell RNA sequencing (scRNA-seq) and mass cytometry (cytometry by time-of-flight, CyTOF) analysis, we also identified the significance of adaptive CD56CD16CD57NKG2C NK cells and classical monocytes (CMs) with chemotaxis traits in orchestrating T-cell immunity in humans. Interestingly, our findings show a deficiency of these adaptive cells in older participants post-booster vaccination, leading to potentially inadequate protection. This study discusses the evaluation of vaccines at the innate immune level, which can contribute to the development of successful vaccines.

Semantics

Original Article