Monoclonal antibodies (MAbs) have been generated which neutralize human immunodeficiency virus type 1 (HIV-1). Results of Phase 1 research indicate that these MAbs recognize three distinct epitopes of the p17 core protein. The precise sequence of each neutralizing site has been determined using peptide scanning techniques. The goal of phase 2 is to provide data for the ultimate construction of HIV-1 vaccines. Using specificity, affinity and viral neutralization as the experimental endpoints, the following immunogens will be studied: synthetic peptides corresponding to p17 neutralizing domains; purified HIV-1 p17 viral protein; and anti-idiotypic antibodies. Immunogens will be administered in the presence of various adjuvant species including T-cell epitopes. The mechanism(s) of action of p17 neutralizing MAbs will be investigated, paying significant attention to viral adsorption/penetration, proviral integration, expression of viral mRNA< and viral budding. Further, antivirals which act at distinct phases of the HIV-1 life cycle will be examined for their capacity to interact in a synergistic manner with p17 neutralizing MAbs. Lastly, the relationship between immunity to p17 determinants and clinical progression of HIV-1 infection will be investigated.
