The long range objective of our research effort is to develop a synthetic peptide vaccine that prevents infection by Human Immunodeficiency Virus, (HIV), the causative agent of Acquired Immunodeficiency Syndrome (AIDS). Based on published reports from other laboratories describing close structural similarities between the HIV envelope protein gp160 and various immunoglobulin gene family members, we predict that the viral surface protein resembles typical immunoglobulin molecules in certain functional aspects. We propose that because of this """"""""molecular mimicry"""""""" exhibited by HIV, the anti-viral antibodies may mask the incoming AIDS virus from immune system attack and even enhance virus infectivity through such phenomenon as Fc receptor mediated entry into monocytic cells, as reported by Takeda et al (4). Therefore, our model for an effective vaccine against HIV is to elicite cell-mediated immunity through a cytotoxic T cell (CTL) response without an anti-viral antibody response (Patent pending). Our working hypothesis for this novel concept is to test in a mouse model system whether synthetic peptides derived from HIV envelope and core proteins can be used as immunogens to elicit a CTL response in the absence of an effective anti-viral antibody response. Specifically, chemically synthesized peptides (10-30 amino acids in length) selected by computer analysis for potential T-cell activity will be prepared as homopolymers prior to inoculation into mice. Our proposal further includes testing whether such CTL epitopes identified in the mouse system can also be recognized by human CTLs specific for HIV infected cells in AIDS patients.
