Speaker
Description
All animal models of HIV-1 are either immunocompromised or rely on the primate virus, SIV. We recently employed tools from population genetics and viral evolution to engineer a host switch of HIV-1 into fully immunocompetent Nancy Ma’s owl monkeys (Aotus nancymaae). These animals can be infected with a minimally modified form of HIV-1, where infection recapitulates key hallmarks of infection in humans. Here, we evaluate if the owl monkey model can be used to evaluate prophylactic protection by performing a passive protection study in the model. Twelve (12) owl monkeys received a single intravenous of the broadly neutralizing antibody 3BNC117 or an isotype control antibody. Twenty-four hours later, all animals were challenged intravenously with HIV-1. Plasma viremia was monitored weekly. For each animal, we assessed the time to peak viremia, peak viral load during the acute phase, viral setpoint, time to seroconversion, and acute-phase depletion of CD4⁺ T cells in the blood and in gut-associated lymphoid tissue (GALT). Infected animals exhibited key hallmarks of HIV-1 infection and pathogenesis as observed in humans. Animals treated with 3BNC117 exhibited significantly delayed or diminished infection parameters compared to controls, with one animal never becoming infected. Further, 4 out of 6 animals that were treated with 3BNC117 before infection became long-term elite controllers, even after the antibody had gone to sub-clinical levels. We employed short-term treatment with the steroid dexamethasone to demonstrate the presence of a reactivatable viral reservoir in these elite controller animals. Finally, we report on the pharmacokinetics of 3BNC117 in owl monkeys, including its presence at mucosal surfaces of the vagina and rectum. These findings underscore the possible future utility of owl monkeys as a model for evaluating prophylactic interventions, including the preclinical optimization of HIV-1 vaccines.
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