IDENTIFYING EPITOPES THAT DEFINE SEROTYPES OF HIV1

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DESCRIPTION: (Adapted from application abstract). Many microorganisms, such as Strep. pneumonia and Polio virus, have been classified into serotypes which have proven useful in vaccine development. Similarly, the characterization of HIV-1 isolates into serotypes should be useful in the development of a polyvalent vaccine against HIV 1. Until now, classification of human immunodeficiency virus (HIV) has been based on its extensive genetic variability, especially in the envelope gene. This has lead to the identification of two genotypic HIV- 1 groups, the major (M) and the outlier (O) groups. Within the M group, 10 genotypes (A-J) have been identified. Genotypes within the O group are yet to be identified. To date, serological classification of HIV has been less extensive than genetic classification. Immunochemical and neutralization assays with sera or monoclonal antibodies (mAbs) and gp 120, gp4 1 subunit proteins, and viruses have been used to study the immunologic relatedness of HIV viruses. Cluster analyses have been applied to the immunochemical and neutralization data generated by independent groups. The results of these analyses suggest that serotypes of HIV-1 do indeed exist and that they do not correlate with genetic subtypes. However, until now, monomeric, recombinant proteins and peptides, rather than the native envelopes represented on virions, have been used for immunochemical analysis. Furthermore, for the neutralization data on which cluster analysis was performed, sera rather than mAbs were used. The applicants propose to examine and develop an immunologic basis for classifying HIV using the following approaches: AIM 1, to describe the antigenic landscape of intact viruses of diverse HIV-1 clades by identifying epitopes that are exposed on the surface of these viruses, and on cells infected with these viruses, by using anti-gpl20 and anti-gp41 mAbs. AIM 2, to define clusters of viruses that are related immunologically (serotypes), to define the epitopes common to these serotypes, and to identify mAbs that can be used in serotyping HIV 1 isolates.