HIV-1 Gag conserved elements presented on MHC molecules (HIV-1 Gag CE/MHC)

HIV-1 Gag conserved elements (CE) presented on MHC molecules are a specialized class of immunological targets used in the development of therapeutic and preventive HIV vaccines. The Gag polyprotein is a structural component of the virus, and specific segments within it are highly conserved across different viral clades because they are critical for viral fitness; mutations in these regions typically lead to non-viable or severely weakened viruses (Mothe et al., 2015, PubMed: 25653454). By presenting these conserved peptides on Major Histocompatibility Complex (MHC) molecules, the immune system can be trained to identify and destroy infected cells using cytotoxic T-lymphocytes (CTLs) (Felber et al., 2014, PubMed: 24920610). This strategy aims to circumvent the challenge of HIV-1's high mutation rate, which allows the virus to escape immune responses targeting more variable regions. Current research focuses on optimizing the delivery of these CE sequences to ensure robust and broad T-cell activation across diverse human populations with varying HLA types (Hanke, 2019, PubMed: 30713130). These targets are primarily addressed through DNA vaccines, viral vectors, and TCR-engineered T-cell therapies. Clinical trials, such as those for the HTI immunogen, evaluate the ability of these targets to control viral rebound in the absence of antiretroviral therapy (NCT03204617). The ultimate goal is to achieve a functional cure by maintaining low viral loads through a focused and potent T-cell response.

Other names

HIV-1 Gag conserved elementsGag-CEConserved HIV-1 Gag epitopesMHC-presented Gag-CE peptidesHIVACAT T-cell Immunogen (HTI)

Induction of CD8+ and CD4+ T-cell responses to recognize and eliminate HIV-infected cells by targeting functionally constrained viral sequences presented on MHC molecules (Mothe et al., 2015, PubMed: 25653454).