Title:

"Identification of HIV antigens for use in an HIV vaccine"

Principal Investigator:

Stephen O. Mathew, Ph.D.

Abstract:

HIV is the retroviral pathogen associated with AIDS, a disease of very high medical significance. Evidence gathered over the natural history of the AIDS pandemic has demonstrated that an effective cytotoxic T-lymphocyte [CTL] response is crucial for immune control of HIV. Furthermore, certain portions of the HIV genome encode proteins that exhibit little to zero tolerance for mutation. These highly conserved peptides are termed structurally constrained epitopes and a dominant CTL response against these epitopes has been associated with resistance to HIV infection and long term non-progression of HIV disease. These epitopes are excellent candidates for a vaccine that stimulates specific CTL responses. Owing to the diversity of the Human Leukocyte Antigen [HLA] class I region, the binding properties and associated immunogenicity of various antigenic epitopes can vary greatly between alleles and the identification of epitopes that stimulate multiple HLA alleles is desirable for vaccine development. The long term goal of this project is to identify multiple constrained HIV antigens that exhibit immunogenicity in respect to multiple HLA alleles and are capable of stimulating an effective CTL response against said alleles. Specific aim 1 proposes to identify MHC-I structurally constrained epitopes and corresponding escape variants that bind multiple HLA class I alleles. Peptide binding assays will evaluate peptide antigenicity. Specific aim 2 proposes to evaluate the ability of structurally constrained epitopes and corresponding escape variants to activate 2B4+ and 2B4¬CD8+ T cells from HIV naïve donors. It is essential to identify constrained HIV epitopes that are capable of stimulating an effective CTL response in the presence of additional constrained epitopes for future incorporation in an epitope specific HIV vaccine.

This project is an effort directed towards identifying portions of HIV that are highly susceptible to attack by cells of the human immune system. Once multiple HIV targets are identified the ability of the immune system to target them at the same time will be studied. Given the high expense of anti retro viral therapy (ART), an inexpensive and effective HIV vaccine is the most viable option for treating and preventing HIV/AIDS among economically disadvantaged populations and minority communities.

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