ANTIBODY/FC RECEPTOR INTERACTIONS IN AIDS MACAQUE MODELS

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DESCRIPTION (provided by applicant): The rhesus macaque represents a major tool for AIDS research and vaccine development. The recent availability of the rhesus macaque genome sequence and microarray chips of macaque-specific genes has certainly increased the potential of the rhesus macaque in biomedical research. However, despite these major improvements, much needs to be done to complete the characterization of this model. Recent findings from passive immunization experiments as well as from experiments performed by depleting B cells in SIV-infected rhesus macaques confirm that antibody responses represent one of the major protective components against infection and disease caused by SIV. Antibodies eliminate pathogens by binding specific antigens with their variable regions and then by activating effector mechanisms through their constant regions. The activation of effector mechanisms occurs through the binding of the constant regions to Fc receptors expressed on a variety of cell types. The various antibody/Fc receptor systems and related pathogen-clearance mechanisms are still largely uncharacterized in nonhuman primate models. Therefore, the objective of this application is the identification of rhesus macaque Fc receptors and the definition of the antibody functional properties that are mediated by these receptors. To accomplish our objective, we will identify Fc receptor genes, express recombinant forms of these receptors in cell lines for the study of antibody/receptor interactions using recombinant rhesus macaque antibody molecules, and assess the ability of rhesus macaque IgG and IgA molecules to trigger specific effector functions. Results from the proposed studies will provide necessary information to accurately assess magnitude and protective efficacy of antibody responses in AIDS macaque models. PUBLIC HEALTH RELEVANCE: The development of an AIDS vaccine represents a public health priority. Although development of such a vaccine requires the use of rhesus macaque models, such models are still uncharacterized. Because antibody responses are known to play a major role in protecting from HIV infection, we propose to characterize antibody/Fc receptor interactions and resulting pathogen clearance mechanisms in rhesus macaques. Results form these studies will provide needed information for the optimal utilization of rhesus macaque models in developing AIDS vaccines.