HIV-1 is transmitted from infected mothers to their infants at a rate of less than 30 percent. The rate of transmission and the expression of disease in the offspring are probably modulated by both humoral and cell-mediated responses in mother and child and by the biologic characteristics of the infecting strain of HIV-1. Previous studies in this laboratory have resulted in the development of an HIV-1 syncytium-inhibition assay which makes use of several unique cell lines. Preliminary work point to a marked difference in the prevalence and titer of syncytium inhibition (SI) antibodies in children who survive longer compared to those who succumb to opportunistic infections in the first 1-2 years of life. It is likely that these SI antibodies exert a protective effect in children and may modulate the rate of vertical transmission. Hence, studies are planned to examine further the relationship between the prevalence and titer of SI antibodies and clinical expression of HIV-1 disease in children. Studies will be expanded to include analysis of maternal sera in order to learn whether SI antibody also affects clinical expression of disease in the mother or alters the rate of vertical transmission. Experiments will also be undertaken to learn whether the titer of SI antibody is affected by the HIV-1 strain used in the target cell system or by the cell type in which the virus resides. Genetic expression systems and both monoclonal and polyclonal antibodies will be used in order to identify the epitopes responsible for eliciting SI antibodies. In order to study the virologic correlates of SI antibody production in women and children, the association between SI antibody titer, plasma and cell-associated viremia and p24 antigen production will be determined. In the process, a variety of HIV-1 strains will be isolated, cultivated, and characterized biologically. These studies have implications for both vaccine development and passive immunotherapy.
