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.

Public Health Relevance

HIV-1 is a global pandemic without a cure. That main barrier to a cure is long-lived latently infected cells that current antiretroviral therapies cannot clear.The proposed research investigates the use of broadly neutralizing anti-HIV-1 antibodies as novel therapy for clearing latently infected cells in both new and chronic infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30AI109830-01A1
Application #
8847152
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Conley, Tony J
Project Start
2014-12-10
Project End
2017-12-09
Budget Start
2014-12-10
Budget End
2015-12-09
Support Year
1
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Administration
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Halper-Stromberg, Ariel; Nussenzweig, Michel C (2016) Towards HIV-1 remission: potential roles for broadly neutralizing antibodies. J Clin Invest 126:415-23