Research Project
3769321
Vaccines which induce enduring immunity have been successful in prevention and control of many serious infectious diseases such as smallpox, measles, and poliomyelitis. Some diseases, such as the Acquired Immunodeficiency Syndrome, present a greater challenge to prevention and control through immunization. Human Immunodeficiency Viruses (HIV) have mechanisms to evade immune responses such as variability through frequent mutation in viral epitopes recognized by neutralizing antibody, viral transmisssion through cell to cell contact (which sequesters virus from neutralizing antibody), and viral destruction or inhibition of cells crucial to regulation of an effective immune response. These problems argue for novel approaches to develop a multivalent vaccine which will induce high titer type and group specific neutralizing antibody and a potent cytotoxic T lymphocyte (CTL) response to conserved HIV epitopes. We will use empirical and theoretical methods such as recognition of T cell epitopes by alphabetical amphipathicity to identify multiple HIV T-helper (Th) epitopes to optimize both boostable neutralizing antibody response and CTL responses and to identify multiple cytotoxic T cell (Tc) epitopes from gag and pol as well as env HIV proteins. We will then design and evaluate the immunologic response to peptide or recombined constructs incorporating Th, Tc, and B cell epitopes in various combinations. As a final objective, we will incorporate promising novel peptide or recombinant constructs into liposomes or into vaccinia virus or BCG vector systems and will compare the immunogenicity of theses candidate vaccines to parenterally administered recombinant proteins containing identical epitopes.
