Therapeutic Applications of Broadly Neutralizing Anti-HIV-1 Antibodies to Clear Latently Infected Cells

Weill Medical Coll Of Cornell Univ, New York NY

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Abstract

? DESCRIPTION (provided by applicant The HIV-1 pandemic is a global emergency for which no cure exists. The early establishment of a latent reservoir of cells harboring replication competent integrated provirus remains the major barrier to a cure. The development of strategies to actively clear infected cells very early in infection could delay, or prevent reservor establishment in newly infected individuals, thereby lengthening the window in which post-exposure prophylaxis (PEP) is effective. The ability to reactivate and clear latently infected cell in chronically infected individuals could decrease reservoir size, thus reducing the lifelong dependence on ART in this population. In both cases, reduction of the latent reservoir is likely to require active killing of HIV-1 infected cells. Antibodies have the ability to mediate clearance of infected cells by antibody-dependent cellular cytotoxicity (ADCC). However, whether or not anti-HIV-1 antibodies can clear infected cells by ADCC in vivo remains unproven. The proposed research investigates the ability of broadly neutralizing anti-HIV-1 antibodies (bNAbs) to clear HIV-1 infected cells in humanized mice, with a specific focus on their ability to alter the establishment and/or size of the latent reservoir. Specifically, this research will investigate: (1 bNAbs' efficacy as post- exposure prophylaxis due to their ability to clear infected cells and prevent reservoir establishment, and (2) bNAbs ability to clear latently infected cells from an established infection when combined with latency reactivating agents.