Dissecting the Protective Effect of CD8⁺ T Cells in Response to SARS-CoV-2 mRNA Vaccination and the Potential Link with Lymph Node CD8⁺ T Cells

Simple Summary Coronavirus disease 2019 (COVID-19) is a respiratory disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has led to millions of deaths globally. The rollout of SARS-CoV-2 vaccines has effectively reduced the morbidity and mortality of COVID-19, with messenger RNA (mRNA)-based vaccines being widely administrated. While neutralizing antibodies are crucial, CD8(+) T cells induced by the vaccine may also play a significant role in early and long-term protection. This review explores the antiviral function of CD8(+) T cells and their response to mRNA vaccines, as well as their role in immune protection in the lymph nodes. SARS-CoV-2 vaccines have played a crucial role in effectively reducing COVID-19 disease severity, with a new generation of vaccines that use messenger RNA (mRNA) technology being administered globally. Neutralizing antibodies have featured as the heroes of vaccine-induced immunity. However, vaccine-elicited CD8(+) T cells may have a significant impact on the early protective effects of the mRNA vaccine, which are evident 12 days after initial vaccination. Vaccine-induced CD8(+) T cells have been shown to respond to multiple epitopes of SARS-CoV-2 and exhibit polyfunctionality in the periphery at the early stage, even when neutralizing antibodies are scarce. Furthermore, SARS-CoV-2 mRNA vaccines induce diverse subsets of memory CD8(+) T cells that persist for more than six months following vaccination. However, the protective role of CD8(+) T cells in response to the SARS-CoV-2 mRNA vaccines remains a topic of debate. In addition, our understanding of CD8(+) T cells in response to vaccination in the lymph nodes, where they first encounter antigen, is still limited. This review delves into the current knowledge regarding the protective role of polyfunctional CD8(+) T cells in controlling the virus, the response to SARS-CoV-2 mRNA vaccines, and the contribution to supporting B cell activity and promoting immune protection in the lymph nodes.