Fig. 3: SARS-CoV-2 natural infection and COVID-19 vaccination.

a | SARS-CoV-2 is transmitted via contaminated air droplets or by contact with contaminated surfaces. The virus encodes four major structural proteins: spike (S), membrane (M), envelope (E) and nucleocapsid (N). The S protein mediates entry into the host cell by binding to angiotensin-converting enzyme 2 (ACE2), which is expressed on different epithelial cells including lung, kidney, gastrointestinal tract, brain and muscle cells. Consequently, multiple organs are susceptible to SARS-CoV-2 infection. The S protein comprises a short intracellular tail and a large ectodomain that includes the receptor-binding domain (RBD) within the S1 subunit and the membrane-fusing S2 subunit. The S, M and N proteins are all known to elicit an immune response. b | Vaccination can be developed using different vaccine platforms, including subunit vaccines or nucleic acid-based (DNA or mRNA) vaccines. In addition to the relevant pathogen-derived antigens, vaccines typically contain adjuvants that stimulate pattern recognition receptors (PRRs). These compounds act on antigen-presenting cells (APCs) to improve antigen uptake, upregulation of MHC molecules, presentation of processed epitopes on MHC molecules and migration to draining lymph nodes, where they present MHC–antigen complexes to T cells. In mRNA-based vaccines, the protein antigen that will be used to activate adaptive immune cells still needs to be produced within host cells (via translation of the vaccine-delivered mRNA) before it can be processed and presented by APCs. Viral vector vaccines require an additional step, as the vaccine-delivered DNA must first be transcribed into mRNA within the host cells, before the aforementioned translation, processing and presentation steps. Under conditions of uraemia and/or immunosuppression, antigenic priming can be impaired through inhibition of APC activation, as well as inhibition of protein synthesis in nucleic acid-based vaccines. MPA, mycophenolic acid.