Phase II year
1990
(last award dollars: 1991)
Monoclonal antibodies (MAbs) have been generated that neutralize human immunodeficiency virus type 1 (HIV-1). Results of Phase I research indicate that these MAbs recognize three distinct epitopes of the pl7 core protein. The precise sequence of each neutralizing site has been determined using peptide scanning techniques. The goal of Phase II 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 pl7-neutralizing domains, purified HIV-1 pl7 viral protein, and anti-idiotypic antibodies. Immunogens will be administered in the presence of various adjuvant species including T-cell epitopes. The mechanisms of action of pl7neutralizing MAbs will be investigated, paying significant attention to viral adsorption/penetration, proviral integration, expression of viral mRNA, and viral budding.Further, antivirals that act at distinct phases of the HIV-1 life cycle will be examined for their capacity to interact in a synergistic manner with pl 7-neutralizing MAbs. Lastly, the relationship between immunity to pl7 determinants and clinical progression of HIV-1 infection will be investigated.Awardee's statement of the potential commercial applications of the research:Identification of novel HIV regions that are involved in neutralization would support new approaches to future vaccines and related therapeutics.National Institute of Allergy and Infectious Diseases (NIAID)