SARS-CoV-2 non-spike peptide-Human Leukocyte Antigen complexes (SARS-CoV-2 pHLA)

SARS-CoV-2–derived peptides from additional viral proteins presented by HLA class I and II represent a critical class of targets for inducing broad and durable cellular immunity against COVID-19. While most first-generation vaccines focus exclusively on the Spike protein, these additional viral proteins—including Nucleocapsid (N), Membrane (M), and various non-structural proteins (NSPs)—contain highly conserved regions that serve as potent T-cell epitopes (Grifoni et al., 2020, Cell). These peptides are processed intracellularly and presented on the cell surface by Human Leukocyte Antigen (HLA) Class I molecules to CD8+ cytotoxic T cells and by HLA Class II molecules to CD4+ helper T cells (Saini et al., 2021, Science Immunology). This presentation is essential for the recognition and elimination of infected cells and the coordination of the overall immune response. Therapeutic strategies targeting these complexes include multi-peptide vaccines like CoVac-1, which are designed to elicit T-cell responses that are less susceptible to viral variant escape (Heitmann et al., 2022, Nature). By focusing on these conserved non-spike proteins, researchers aim to develop universal vaccines that provide protection across different SARS-CoV-2 lineages and potentially other coronaviruses (Nagler et al., 2021, Journal of Clinical Investigation).

Other names

SARS-CoV-2 T-cell epitopesSARS-CoV-2 HLA ligandsNon-spike SARS-CoV-2 antigensSARS-CoV-2 immunopeptidomeCoVac-1 peptides

Presentation of viral peptides by HLA molecules to T-cell receptors (TCRs), inducing cellular immunity.