Dan H. Barouch, M.D., Ph.D.

Associate Professor of Medicine

Division of Viral Pathogenesis
Beth Israel Deaconess Medical Center
Tel: 617-667-4434
Fax: 617-667-8210
email: dbarouch@bidmc.harvard.edu
7 postdocs, 2 predocs

My laboratory focuses on the immunopathogenesis of HIV-1 and the development of HIV-1 vaccine strategies.  We have developed and assessed novel vaccine strategies based on plasmid DNA vaccines, recombinant poxvirus vectors, and recombinant adenovirus vectors in both mice and nonhuman primates.  In particular, we have demonstrated that adjuvanted DNA vaccines and viral vector-based vaccines elicit potent cellular immune responses that can control pathogenic AIDS virus challenges in rhesus monkeys (1).  These results suggest that HIV-1 vaccines that generate potent cellular immune responses may provide significant clinical benefits even if they fail to provide sterilizing immunity.  We have also shown that viral mutations can develop that result in viral escape from immune control and eventual AIDS vaccine failure (2).  We are currently studying the safety and immunogenicity of adjuvanted DNA vaccines in phase 1 prophylactic and therapeutic vaccine studies in collaboration with the NIH Vaccine Research Center (VRC), HIV Vaccine Trials Network (HVTN), and AIDS Clinical Trials Group (ACTG).  My laboratory also focuses on the generation and evaluation of novel serotype and novel chimeric adenovirus vector-based vaccines for HIV-1 (3-5).  As part of an NIH Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) program and a Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CAVD) program, we are advancing a series of novel adenovirus vectors for HIV-1 into nonhuman primate challenge studies and phase 1 clinical trials.

References:

Barouch DH, Santra S, Schmitz JE, Kuroda MJ, Fu TM, Wagner W, Bilska M, Craiu A, Zheng XX, Krivulka GR, Beaudry K, Lifton MA, Nickerson CE, Trigona WL, Punt K, CE, Freed DC, Guan L, Dubey S, Casimiro D, Simon A, Davies ME, Chastain M, Strom TB, Gelman RS, Montefiori DC, Lewis MG, Emini EA, Shiver JW, Letvin NL.  Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination.  Science 2000; 290:486-492.

Barouch DH, Kunstman J, Kuroda MJ, Schmitz JE, Santra S, Peyerl FW, Krivulka GR, Beaudry K, Lifton MA, Gorgone DA, Montefiori DC, Lewis MG, Wolinsky SM, Letvin NL.  Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes.  Nature 2002; 415:335-339.

Sumida SM, Truitt DM, Lemckert AAC, Vogels R, Custers JHHV, Addo MM, Lockman S, Peter T, Peyerl FW, Kishko MG, Jackson SS, Gorgone DA, Lifton MA, Essex M, Walker BD, Goudsmit J, Havenga MJE, Barouch DH.  Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein.  J. Immunol. 2005; 174:7179-7185.

Roberts DR, Nanda A, Havenga MJE, Abbink P, Lynch DM, Ewald BA, Liu J, Thorner AR, Swanson PE, Gorgone DA, Lifton MA, Lemckert AAC, Holterman L, Chen B, Dilraj A, Carville A, Mansfield KG, Goudsmit J, Barouch DH.  Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity.  Nature 2006; 441:239-243.

Thorner AR, Lemckert AAC, Goudsmit J, Lynch DM, Ewald BA, Denholtz M, Havenga MJE, Barouch DH.  Circumventing vector cross-reactivity enhances the immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens.  J. Virol. 2006; 80:12009-12016.