IMPORTANCE OF ANTIBODY ISOTYPE IN VAGINAL HIV TRANSMISSION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. It is now clear that intestine and other mucosal tissues are of major importance in both the transmission as well as the early pathogenesis of HIV infection. These studies were initiated to determine if antibodies of different isotypes were better for protecting the vaginal vault, and performed experiments to determine if there was preferential secretion and we have now demonstrated that HIV-specific IgA and IgG are preferentially secreted from the intestine (rectum) and vagina, respectively following intravenous administration, and that following parenteral administration, up to 10ug/ml monoclonal antibodies can be detected in mucosal tissues 6-12 hr after administration to macaques. However, we could not detect sufficient IgA secretion in the vagina after parenteral administration, consistent with the hypothesis that IgA is produced in significant quantities in vaginal secretions. Although informative, this prevented the original study from completion and we have now switched directions to pursuing mechanisms of mucosal antibody protection, especially with MPER antibodies.