MUCOSAL SECRETION KINETICS OF THE PG9 BROADLY NEUTRALIZING ANTIBODY AGAINST HIV

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Objective: To assess the systemic and mucosal pharmacokinetics of antibody PG9. Most successful anti-viral vaccines induce neutralizing antibodies, which are typically a strong correlate of protection. For HIV, it has been shown that passive transfer of neutralizing antibodies can provide protection against viral challenge in the best available animal models. Therefore, it is widely argued that the elicitation of a neutralizing antibody response will be a crucial component of an effective vaccine against HIV. Such antibodies should be broadly neutralizing given the diversity of viruses to which a vaccinee may be exposed. The antibody PG9 displays a remarkable combination of breadth and potency that suggests that vaccine-induced antibodies of this type would likely provide protection at serum concentrations that would be achievable by vaccination. Thus, PG9 will likely be useful reagent for understanding Env structure, conformation, and function. These studies have, in particular, illuminated the potential of conserved regions of the V2 and V3 loop of gp120 to serve as a target for immunogen design. PROGRESS: Two animals were passively infused with the PG9 antibody. Blood and mucosal antibody levels were determined by sampling for 14 days following passive infusion. The obtained results confirmed the transport of the antibodies into the mucosal lumen. Data from this study will be used in the final protocol design for the passive infusion in SHIV viral challenge studies. This research used Animal Services, CPI and Immunology Services. PUBLICATIONS: None.