IMMUNOLOGIC RELATEDNESS AMONG AND BETWEEN HIV1 CLADES

New York University School Of Medicine, New York NY

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Abstract

An AIDS vaccine must induce immunity against the diverse types of human immunodeficency virus-type 1 (HIV) which exist throughout the world. This diversity is reflected in the antigenic variability of HIV and poses a major obstacle to the development of a vaccine which will be effective globally. Scant information available about the epitopes shared between diverse isolates that elicit neutralizing antibodies (Abs) which are thought to play a protective role against HIV infection. The work proposed is designed to elucidate the antigenic variability of the HIV envelope glycoproteins and to identify shared epitopes recognized by Abs in order to determine if there are HIV immunotypes (virus groups that can be identified on the basis of common B cells epitopes) and HIV neutrotypes (virus groups related by their pattern of Ab-mediated neutralization). For this, human monoclonal antibodies (mAbs) will be particularly useful because they reflect the human B cell repertoire and are exquisitely specific. To date, all but one human anti-HIV mAbs come from subjects infected with viruses from a single class of HIV (clade B). The study of the one human mAb from a clade E- infected individual demonstrates that mAbs derived from the cells of individuals infected with diverse stains of HIV will reveal novel information about both shared and unique HIV envelope epitopes, and will provide a much more complete analysis of the antigenic structure of the HIV virion. Therefore, as our specific aims, we will: (1) produce human mAbs from blood specimens from HIV-infected subjects provided by collaborators in Cameroon where essentially all known types of HIV exist in the infected population. For this we will include a new technique designed to select for an increased proportion of neutralizing Abs that are directed against epitopes exposes on the surface of intact virions; (2) use the newly derived mAbs and greater than 60 previously described human anti-HIV mAbs to identify by immunochemical and functional assays the antigenic structures of the HIV envelope which are shared by diverse primary isolates; 3) mathematically analyze the data to identify immunotypes, neutrotypes and key isolates that will be useful in constructing an HIV vaccine of global utility.