The Laboratory for AIDS Vaccine Research and Development is led by David Montefiori, PhD. One of this lab's highest priorities is to identify immunogens that generate broadly cross-reactive neutralizing antibodies against HIV-1 for inclusion in vaccines.
Many aspects of neutralizing antibodies are studied in this laboratory, including mechanisms of neutralization and escape, epitope diversity among the many different genetic subtypes and geographic distributions of the virus, broadly neutralizing epitopes, developmental pathways leading to broadly neutralizing antibody production, and computationally-assisted vaccine design. Over the years, the laboratory has explored multiple technologies for measuring neutralizing antibodies and other potential antiviral antibodies, focusing on assay optimization, standardization, validation and high throughput.
For the past two decades, the laboratory has served as a national and international resource for standardized assessments of neutralizing antibody responses in preclinical and clinical trials of candidate AIDS vaccines.
The laboratory is funded by the National Institutes of Health as part of several initiatives:
The laboratory also receives funding from the Bill and Melinda Gates Foundation as part of the Collaboration for AIDS Vaccine Discovery (CAVD).
Section for AIDS Research and Development faculty within the Division of Surgical Sciences are:
- Defined the autologous and heterologous neutralizing antibody response to HIV-1 infection. These findings demonstrated that HIV-1 broadly neutralizing antibody responses are possible and provided a rationale for the discovery of a new generation of broadly neutralizing antibodies and their epitopes.
- Pilgrim, A.K., G. Pantaleo, O.J. Cohen, L.M. Fink, J.Y. Zhou, J.T. Zhou, D.P. Bolognesi, A.S. Fauci, and D.C. Montefiori. (1997) Neutralizing antibody responses to human immunodeficiency virus type 1 in primary infection and long-term nonprogressive infection. J. Infect. Dis., 176:924-932.
- Tang, H., J.E. Robinson, S. Gnanakaran, M. Li, E.S. Rosenberg, L.G. Perez, B.F. Haynes, H.-X. Liao, C.C. LaBranche, B.T. Korber, and D.C. Montefiori. (2011) Epitopes immediately below the base of the V3 loop of gp120 as a targets for the initial autologous neutralizing antibody response in two subtype B HIV-1-infected individuals. J. Virol., 85:9286-9299.
- Hraber, P., M.S. Seaman, R.T. Bailer, J.R. Mascola, D.C. Montefiori, B.T. Korber. (2014) Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS, 28:163-169.
- Hraber, P., B.T. Korber, A.S. Lapedes, R.T. Bailer, M.S. Seaman, H. Gao, K.M. Greene, F. McCutchan, C. Williamson, J.H. Kim, S. Tovanabutra, B.H. Hahn, R. Swanstrom, M.M. Thomson, F. Gao, L. Harris, E. Giorgi, N. Hengartner, T. Bhattacharya, J.R. Mascola, and D.C. Montefiori. (2014) Impact of clade, geography, and age of the epidemic on HIV-1 neutralization by antibodies. J. Virol., 88:12623-12643.
- Developed highly standardized and formally validated assays to assess HIV-1 vaccine-elicited neutralizing antibody responses. These assays were used to define the magnitude and breadth of vaccine-elicited neutralizing antibody responses in preclinical and human clinical trials. The results highlight the limitations of current vaccine immunogens and emphasize the extraordinary challenge in designing an effective HIV-1 vaccine.
- Montefiori, D.C. (2009) Measuring HIV neutralization in a luciferase reporter gene assay. HIV Protocols: Second Edition, Methods in Molecular Virology (Vinayaka R. Prasad, Ganjam V. Kalpana, eds.), Humana Press, 485:395-405.
- Sarzotti-Kelsoe, M., R.T. Bailer, E. Turk, C.L. Lin, M. Bilska, K.M. Greene, H. Gao, C.A. Todd, D.A. Ozaki, M.S. Seaman, J.R. Mascola and D.C. Montefiori. (2014) Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1. J. Immunol. Meth., 409:131-146.
- Gilbert, P., M. Wang, T. Wrin, C. Petropoulos, M. Gurwith, F. Sinangil, P. D'Souza, I.R. Rodriguez-Chavez, A. DeCamp, M. Giganti, P.W. Berman, S.G. Self, and D.C. Montefiori. (2010) Magnitude and breadth of a nonprotective neutralizing antibody response in an efficacy trial of a candidate HIV-1 gp120 vaccine. J. Infec. Dis., 202:595-605.
- Montefiori, D.C., C. Karnasuta, Y. Huang, H. Ahmed, P. Gilbert, M.S. de Souza, R. McLinden, S. Tovanabutra, A. Laurence-Chenine, E. Sanders-Buell, M.A. Moody, M. Bonsignori, C. Ochsenbauer, J. Kappes, H. Tang, K. Greene, H. Gao, C.C. LaBranche, C. Andrews, V.R. Polonis, S. Rerks-Ngarm, P. Pitisuttithum, S. Nitayaphan, J. Kaewkungwal, S.G. Self, P.W. Berman, D. Francis, F. Sinangil, C. Lee, J. Tartaglia, M.L. Robb, B.F. Haynes, N.L. Michael, and J.H. Kim. (2012) Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials. J. Infec. Dis., 206:431-441.
- Developed robust panels of HIV-1 Env-pseudotyped viruses that have facilitated standardized assessments of vaccine-elicited neutralizing antibody responses.
- Li, M., F. Gao, J.R. Mascola, L. Stamatatos, V.R. Polonis, M. Koutsoukos, G. Voss, P. Goepfert, P. Gilbert, K.M. Greene, M. Bilska, D.L. Kothe, J.F. Salazar-Gonzalez, X. Wei, J.M. Decker, B.H. Hahn, and D.C. Montefiori. (2005) Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol., 79:10108-10125.
- Li, M., J.F. Salazar-Gonzalez, C.A. Derdeyn, L. Morris, C. Williamson, J.E. Robinson, J.M. Decker, Y. Li, M.G. Salazar, V.R. Polonis, K. Mlisana, S.A. Karim, K. Hong, K.M. Greene, M. Bilska, J.T. Zhou, S. Allen, E. Chomba, J. Mulenga, C. Vwalika, F. Gao, M. Zhang, B.T.M. Korber, E. Hunter, B.H. Hahn, and D.C. Montefiori. (2006) Genetic and neutralization properties of subtype C human immunodeficiency virus type 1 molecular env clones from acute and early heterosexually acquired infections in southern Africa. J. Virol., 80:11776-11790.
- Seaman, M.S., H. Janes, N. Hawkins, L.E. Grandpre, C. Devoy, A.Giri, R.T. Coffey, L. Harris, B. Wood, M.G. Daniels, T. Bhattacharya, A.Lapedes, V.R. Polonis, F.E. McCutchan, P.B. Gilbert, S.G. Self, B.T. Korber, D.C. Montefiori, and J.R. Mascola. (2010) Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessments of neutralizing antibodies. J. Virol., 84:1439-1452.
- DeCamp, A., P. Hraber, R.T. Bailer, M.S. Seaman, C. Ochsenbauer, J. Kappes, R. Gottardo, P. Edlefsen, S. Self, H. Tang, K. Greene, H. Gao, X. Daniell, M. Sarzotti-Kelsoe, M.K. Gorny, S. Zolla-Pazner, C.C. LaBranche, J.R. Mascola, B.T. Korber, D.C. Monteï¬ori. (2014) Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol., 88:2489-2507.
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