BNT162b2 COVID-19 vaccination elicits the expansion of CD16+CD8+ T cells endowed with Natural Killer cell features

Background: The Pfizer/BioNtech vaccine, also known as BNT162b2, was developed using a novel technology based on mRNA and protects against COVID-19 via induction of specific antibody and T-cell responses. Much less is known about the broader effects of this new class of vaccines on unconventional cellular components of the immune system. Objective: We aimed to characterize a subset of unconventional T cells emerging upon BNT162b2 mRNA vaccination. Methods: Peripheral blood from a total of 30 human healthy individuals who received two doses of the BNT162b2 mRNA vaccine was collected for the analysis of T cell compartment by using multiparametric flow cytometry and single-cell transcriptome analyses. Results: In the peripheral blood of individuals undergoing BNT162b2 vaccination, we observed a sizable fraction of CD8+ T cells expressing CD16, a low-affinity FcR for IgG. These cells were SARS-CoV-2 specific, characterized by interferon gamma (IFN-γ) response gene transcripts and stimulation through CD16 and other NK cell innate receptors elicited a functional response. Both CD16 and NKp30 could be induced on NKp80+ CD8+ T cells and the engagement of NKp80 in combination with CD16 resulted in synergic effects. CD16+ CD8+ T cells also showed a high expression of the inhibitory receptor GPR56, capable of limiting their activation via CD16. Conclusion: These data indicate that BNT162b2 COVID-19 vaccination provides an additional large fraction of antibody-dependent cellular cytotoxicity (ADCC)-capable effector cells, endowed with innate functions and therefore able to potentially counteract a much wider array of diseases, including cancer.