Abstract

A lack of neutralizing antibodies distinguishes HIV-1 from most other viral pathogens and is responsible to a large degree for the ability of HIV-1 to maintain a persistent infection. A few monoclonal antibodies have been isolated that are broadly neutralizing. We have used X-ray crystallography to investigate the epitopes of broadly neutralizing antibodies and their mechanisms of neutralization. In particular, we have examined CD4-induced (CD4i) antibodies that recognize the coreceptor-binding site, membrane-proximal-binding antibodies like 2F5, and CD4-binding-site antibodies like b12. The b12 analysis lead to the identification of a site of vulnerability to neutralizing antibody on HIV-1, which we are now pursuing as a prime vaccine target.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005022-07
Application #
7732745
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2008
Total Cost
$478,295
Indirect Cost

  Institution

Name
National Institute of Allergy and Infectious Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Kong, Leopold; Sattentau, Quentin J (2012) Antigenicity and Immunogenicity in HIV-1 Antibody-Based Vaccine Design. J AIDS Clin Res S8:3
Davis, Katie L; Bibollet-Ruche, Frederic; Li, Hui et al. (2009) Human immunodeficiency virus type 2 (HIV-2)/HIV-1 envelope chimeras detect high titers of broadly reactive HIV-1 V3-specific antibodies in human plasma. J Virol 83:1240-59
Zhou, Tongqing; Xu, Ling; Dey, Barna et al. (2007) Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445:732-7
Huang, Chih-Chin; Lam, Son N; Acharya, Priyamvada et al. (2007) Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science 317:1930-4
Decker, Julie M; Bibollet-Ruche, Frederic; Wei, Xiping et al. (2005) Antigenic conservation and immunogenicity of the HIV coreceptor binding site. J Exp Med 201:1407-19
Huang, Chih-chin; Tang, Min; Zhang, Mei-Yun et al. (2005) Structure of a V3-containing HIV-1 gp120 core. Science 310:1025-8
Zhou, Tongqing; Hamer, Dean H; Hendrickson, Wayne A et al. (2005) Interfacial metal and antibody recognition. Proc Natl Acad Sci U S A 102:14575-80
Venter, Marietjie; Myers, Timothy G; Wilson, Michael A et al. (2005) Gene expression in mice infected with West Nile virus strains of different neurovirulence. Virology 342:119-40
Huang, Chih-chin; Venturi, Miro; Majeed, Shahzad et al. (2004) Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120. Proc Natl Acad Sci U S A 101:2706-11
Kwong, Peter D (2004) The 447-52D antibody: hitting HIV-1 where its armor is thickest. Structure 12:173-4

Showing the most recent 10 out of 13 publications