SARS-CoV-2 Spike, Membrane, Nucleocapsid, NSP4, and Accessory protein 7a antigenic peptides presented on HLA molecules (SARS-CoV-2 multi-antigen pHLA)

The target consists of a specific set of antigenic peptides derived from five SARS-CoV-2 proteins—Spike (S), Membrane (M), Nucleocapsid (N), Non-structural protein 4 (NSP4), and Accessory protein 7a (AP7a/ORF7a)—presented on the surface of infected cells by Human Leukocyte Antigen (HLA) molecules (Grifoni et al., 2020, Cell). These peptides are processed intracellularly and loaded onto MHC Class I or II molecules, serving as recognition elements for the cellular immune system (Saini et al., 2021, Science Immunology). By targeting multiple antigens simultaneously, therapeutic approaches aim to provide broad protection and reduce the likelihood of viral escape through mutations, a common limitation of Spike-only vaccines (Marker Therapeutics, 2020). This target is primarily utilized in the development of Multi-Antigen-Specific T-cell (MAST) therapies and T-cell receptor (TCR) based interventions. Drugs interacting with this target, such as adoptive T-cell therapies like Marker Therapeutics' COVID-19 MAST, work by recognizing these specific pHLA complexes via expanded T-cell receptors, leading to the direct lysis of SARS-CoV-2 infected cells and the secretion of pro-inflammatory cytokines. This approach is particularly relevant for immunocompromised patients who cannot mount an effective endogenous immune response to the virus.

Other names

SARS-CoV-2 S/M/N/NSP4/ORF7a HLA-peptide complexesCOVID-19 multi-antigen-specific T-cell targetSARS-CoV-2 multi-antigen T-cell epitopesSARS-CoV-2 pHLA complexes

T-cell receptor-mediated recognition of HLA-presented viral peptides leading to cytotoxic T-lymphocyte (CTL) activation and lysis of infected cells.