SBIR-STTR Award

Monoclonal antibodies have been generated which react with conserved sites of the p17 core protein of the human immunodeficiency virus (HIV). Two of these antibodies exert a potent neutralizing effect on the replication of HIV in permissive cells. The goals of this proposal are to (1) precisely identify the p17 epitopes recognized, (2) synthesize peptides which span the epitopes of interest, (3) generate idiotypic reagents corresponding to the biologically active antibodies and to (4) characterize the antipeptide antisera and idiotypic antibodies for HIV neutralization and inhibition of viral adsorption to target receptors Methodologies for achieving these goals include epitope mapping, peptide synthesis, monoclonal and polyclona antibody development and the use of HIV transmission assays and viral adsorption procedures. A comparative evaluation of the biological efficac of antipeptide versus idiotypic antibodies will result, along with information relating to novel sites on HIV structures which are amenable t neutralization.National Institute of Allergy and Infectious Diseases (NIAID)

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)