Nicolas Chomont, Ph.D.
Immunotherapies & HIV Cure
Nicolas Chomont, Ph.D., is a principal investigator at the Vaccine & Gene Therapy Institute of Florida (VGTI Florida®,). He is an internationally recognized scientist who specializes in HIV and AIDS research. His work has contributed to advancements in the understanding of how HIV infections persist, despite effective anti-HIV medications wiping out detectable levels of the virus – an important step in eradicating the disease.
Dr. Chomont also helped identify the role of a protein called FOXO3a in the persistence of the HIV virus in infected T cells. His current research is focused on defining mechanisms and potential drug targets that could lead to the eradication of persistent HIV and an eventual cure for HIV infection.
His work has been recognized with a number of prestigious awards, including earning an American Foundation for AIDS Research post-doctoral fellowship. He was awarded a post-doctoral fellowship by the Louis Pasteur Foundation in Canada, and a fellowship by the National Agency for AIDS Research in France.
Dr. Chomont earned his bachelor’s degree in biological sciences, a master’s degree in biochemistry and his doctorate in virology all at the University of Paris. Prior to arriving at VGTI Florida, he completed his post-doctoral fellowship at the University of Montreal.
Laboratory of Dr. Nicolas Chomont
Our group is investigating the mechanisms by which HIV persists in HIV infected individuals receiving Highly Active Antiretroviral Therapy (HAART) in order to develop novel therapeutic strategies aimed at eradicating the virus.
Advances in the treatment of HIV infection have dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected patients. The initiation of HAART results in a rapid drop in plasma viral load and in a substantial reduction in the number of cells carrying proviral DNA in both blood and tissues. However, it is now clear that HAART does not eradicate HIV, the spread of the virus almost immediately resumes upon cessation of HAART in all but exceptional cases.
Figure 1: Current anti-HIV drugs do not eradicate HIV
Two non-mutually exclusive mechanisms underlie this persistence in patients who have received suppressive HAART for extended periods of time (Figure 2).
The incomplete suppression of viral replication by current treatments could allow the continuous replenishment of a small pool of infected cells, particularly in anatomical compartments in which drug penetration may not be optimal.
The existence of a small pool of latently infected resting memory CD4+ T cells, from which the virus may resurge upon exposure to different external triggers, shows little or no decay even after prolonged HAART. We have recently shown that T cell survival and homeostatic proliferation ensure the persistence of these cells.
The precise mechanisms responsible for the persistence of HIV in blood and more importantly in tissues such as gut and lymph nodes, which are preferential sites for HIV persistence, are largely unknown. Therefore, it is important to characterize these mechanisms to design therapeutic strategies aimed at eradicating HIV.
To achieve this goal, we are currently undergoing the following studies:
Figure 2: Mechanisms contributing to HIV persistence
Investigating the impact of homeostatic proliferation on HIV persistence.
We are evaluating the capacity of inhibitors of IL-7 to interfere with the persistence of latently infected cells by affecting the survival of central memory CD4 T cells (TCM); in parallel, we are assessing the impact of IL-15 on inducing the decay of the HIV reservoir by inducing the differentiation of TCM who are quiescent and latently infected into the more differentiated TEM cells which are more likely to produce viral proteins, and consequently, to be eliminated.
The role of negative regulators of T cell activation in the maintenance of viral latency.
The main objective of this study is to determine whether the negative regulators CTLA-4, PD-1, and Tim-3 can identify latently infected CD4 T cells in HIV patients receiving suppressive ART and whether blocking these negative pathways ex vivo can reactivate viral production.
Identifying the antigen specificity of the latent reservoir: A rationale for the development of vaccine aimed at activating HIV-specific CD4 T cell.
The goal of this study is to determine if the stimulation of latently infected cells with HIV antigen is a potent strategy to reduce the HIV reservoir magnitude. This study would constitute a proof of concept for the development of a clinical trial aimed at reducing the pool of latently infected cells in HIV infected subjects by immunization with HIV antigen (with or without blocking antibodies to negative regulators of T cell activation).
Screening of small molecules aimed at reactivating HIV from its latent reservoirs
We are evaluating the potency of small molecules to reactivate HIV from latency. We have developed a unique in vitro system using primary CD4 T cells from subjects receiving suppressive HAART aimed at measuring viral production from stable reservoir upon incubation with chemical compounds, cytokines or antibodies.
Nicolas Chomont, Ph.D.
Vaccine & Gene Therapy Institute of Florida
9801 SW Discovery Way
Port St. Lucie, FL 34987
Tel: (772) 345-5672
Fax: (772) 345-5753
Remi Fromentin, Pharm.D., Ph.D., Post-doctoral Fellow
Wendy Bakeman, B.S., Research Assistant
Amanda McNulty, B.S., Research Assistant
Chomont, N., M. El-Far, P. Ancuta, L. Trautmann, F. A. Procopio, B. Yassine-Diab, G. Boucher, M. R. Boulassel, G. Ghattas, J. M. Brenchley, T. W. Schacker, B. J. Hill, D. C. Douek, J. P. Routy, E. K. Haddad, and R. P. Sekaly. 2009. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15:893-900. PMID:19543283
Chomont, N., S. DaFonseca, C. Vandergeeten, P. Ancuta, and R. P. Sekaly. 2011. Maintenance of CD4+ T-cell memory and HIV persistence: keeping memory, keeping HIV. Curr Opin HIV AIDS 6:30-36. PMID:21242891
Trono, D., C. Van Lint, C. Rouzioux, E. Verdin, F. Barre-Sinoussi, T. W. Chun, and N. Chomont. 2010. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 329:174-180. PMID:20616270
Lewin, S. R., V. A. Evans, J. H. Elliott, B. Spire, and N. Chomont. 2011. Finding a cure for HIV: will it ever be achievable? J Int AIDS Soc 14:4. PMID:21255462