The number of cases of AIDS in children has been projected to be over 3,000 by 1991 by the Centers for Disease Control. It is a major priority to develop therapeutic reagents which would be of benefit to this population. Of similar importance is understanding how to reduce the transmission of HIV from infected pregnant mothers to their children. The ability of several specific peptides corresponding to defined regions of gp120 and 41, including the V3 loop region, to induce protective in vitro immune responses in experimental animals argues that a complete understanding of the complex nature of the anti-HIV envelope responses will enable development of immunologically relevant strategies which will benefit HIV infected individuals. The observation that some HIV infected pregnant women who possess high antibody responses to the HIV envelope glycoprotein do not transmit infection to their fetus suggests that antibody based therapy may have clear clinical implications for the treatment of HIV infected individuals. Just as important, individual peptide based immunogens may be considered as therapeutics which if clearly defined would have the potential to significantly boost this specific protective immunity. In fact, therapeutic success has been observed following intravenous immunoglobulin treatment of HIV-infected children. These studies indicate that there exist potential protective humoral immune responses which if developed in the mother may confer to the fetus protection from HIV infection. Currently, there exists an incomplete understanding of the nature of protective epitopes and maternal HIV transmission. Furthermore, it is important to consider the limitation that only the human population of infected individuals is available as a source of human anti-HIV specific antibody. Elucidating the site specific serological basis of the maternal immune response as it correlates with protection from fetal transmission is the direct goal of this proposed study. The further goal is to construct functionally relevant antibody populations which will ultimately give insight into immunological design of reagents useful in passive immune therapy.
