SARS-CoV-2 mRNA Vaccines: Immunological Mechanism and Beyond

Abstract

To successfully protect against pathogen infection, a vaccine must elicit efficient adaptive immunity, including B and T cell responses. While B cell responses are key, as they can mediate antibody-dependent protection, T cells can modulate B cell activity and directly contribute to the elimination of pathogen-infected cells. In the unprecedented race to develop an effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the respiratory disease coronavirus disease 2019 (COVID-19), messenger RNA (mRNA) vaccines have emerged as front runners thanks to their capacity for rapid development and ability to drive potent adaptive immune responses. In this review article, we provide an overview of the results from pre-clinical studies in animal models as well as clinical studies in humans that assessed the efficacy of SARS-CoV-2 mRNA vaccines, with a primary focus on adaptive immune responses post vaccination.

Keywords: SARS-CoV-2; T follicular helper cells; Th1 cells; adaptive immunity; antibodies; coronavirus; germinal centers; long-lived plasma cells; mRNA vaccines; memory B cells.

Figure 1

Immune responses elicited by SARS-CoV-2 mRNA vaccines. SARS-CoV-2 mRNA vaccines are administered intramuscularly (1). Either mRNA-LNPs or locally produced antigen are taken up by antigen-presenting cells (APCs) (2), such as dendritic cells (DCs). These APCs then traffic to the lymph nodes (3) where they are able to prime CD4 and CD8 T lymphocytes (4). The events in (2)–(4) are reviewed in detail in [36]. The priming of CD8 T cells can induce the formation of cytotoxic T lymphocytes (5b) which are capable of directly killing infected cells. Antigen-primed CD4 T cells can differentiate into Th1 cells (5a) or T follicular helper (Tfh) cells. Tfh cells help to initiate a germinal center (GC) reaction (6). GC reactions induced by vaccination will result in the formation of affinity-matured memory B cells (MBCs) and the antibody-secreting long-lived plasma cells (LLPCs). Tfh cells can be skewed towards either a Th1 or Th2 phenotype, which will affect the class switching of antibodies (Abs) produced by LLPCs to either Th1- or Th2-associated Abs (6).