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 determine the role of the protective antibodies in killing and eliminating the infected cells. Also, to determine whether the protection against SHIV infection is better if one of these functions of antibodies -- either killing or eliminating infected cells -- is enhanced. (This project includes two main experiments.) In the current studies we use the recombinant Simian Human Immunodeficiency Virus (SHIV) infected-Rhesus macaque model to understand the role of two different functions of the protective antibodies against HIV infection in humans. For the first objective, we will treat two groups of animals with two different, but closely related antibodies that were genetically engineered to perform either the killing or the eliminating function well. We will compare the control of viremia in these two groups of animals and between three other groups of animals. One of the latter three groups of animals will not be treated with any antibody, the other group will be treated with an antibody that has both functions, and the third group will be treated with an antibody that has protective activity, but lacks killing activity and does not facilitate the eliminating of the infected cells either. For the second objective, we will treat two groups of animals with two different, but closely related antibodies that were genetically engineered to perform just one of these two functions at an enhanced level. We will compare the control of viremia in the two groups of animals and between groups of animals that will not be treated with any antibody, or will be treated with an antibody that has both functions at a normal level. PROGRESS: We have performed two pilot experiments. In the first pilot experiment, we titrated the new SHIV162P3 virus stock in vivo to determine the challenge dose that we will use in the main experiments. In the second pilot experiment, we determined the secretion kinetics of antibody NFb12 from the blood into the vaginal lumen. NFb12 antibody is a variant of the broadly neutralizing HIV antibody b12. Its Fc domain has been modified to enhance ADCC and phagocytosis. We have started the second experiment to determine the neutralization capabilities of antibody NFb12. We use a low concentration (1 mg/kg) of infused NFb12 against repeated low dose SHIV162P3 challenges. This research used Animal Services, CPI, and Virology &Immunology Services. PUBLICATIONS: None.
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