The paradoxical absence of uniform infection in infants of HIV-infected women makes it likely that maternal or fetal immune function may influence vertical transmission of virus. The same immune responses may facilitate early diagnosis of infection in the infant. We shall study the role of anti-HIV antibody-dependent cellular cytotoxicity(ADCC) and IgA in virus transmission and early diagnosis respectively. The role of ADCC will be studied to correlate HIV-ADCC titers in the mother and child with virus transmission, to characterize possible material serum blocking factors against ADCC, to identify the crucial, HIV ADCC antibody epitopes and then develop epitope-specific profiles of maternal and infant sera. This is possible using our well standardized HIV ADCC assay using chronically infected target cells, and with the availability of well characterized monoclonal antibodies to HIV envelope epitopes. ADCC strain-specificity and HIV ADCC escape variants will be sought using laboratory and autologous viral strains. Fetal and healthy, as well as HIV-at-risk, newborns' ADCC effector cell function will be analyzed, compared, and assayed for response to potential cytokine upregulation. The presence of anti-HIV IgA antibody in infected and uninfected babies will be analyzed to determine it's utility for reliable early diagnosis. Prospectively followed HIV-at-risk infants will be studied for the presence of HIV infection by serial cultures, PCR and ELISA and Western Blot antibody analysis. Anti-HIV IgA will be detected by ELISA and dot blot assays using recombinant HIV antigens, and with or without IgG adsorption. The origin of anti-HIV IgA will be tested by sequential analysis of salivary and serum samples, and IgA subclasses and ELISPOT analysis of individual peripheral blood mononuclear cells for specific anti-HIV IgA production, to localize the IgA response. These studies should clarify the role of ADCC antibody in prevention of HIV transmission from mother to infant, and the role of HIV-IGA antibody in early diagnosis and therapy of the at-risk infant.
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