MOLECULAR STUDIES OF HIV1 NEUTRALIZING ANTIBODIES

Summary

Principal Investigator: Joseph G Sodroski
Affiliation: Harvard University
Country: USA
Abstract: The gp120 and gp41 envelope glycoproteins of human immunodeficiency virus (HIV-1), the etiologic agent of acquired immunodeficiency syndrome (AIDS), plays important roles in virus entry into target cells and viral cytopathic effects. Since the HIV-1 envelope glycoproteins are exposed on the virion, they represent critical targets for therapeutic intervention and vaccine development. Antibodies that neutralize virus infectivity in vitro and that, in some cases, have been shown to be protective in vivo are directed against both variable and conserved regions of the HIV-1 envelope glycoproteins. The relatively well- conserved discontinuous epitopes on the HIV-1 gp120 glycoprotein constitute attractive targets for immunological intervention, but have been proven difficult to elicit antibodies against. The goal of this proposal is to capitalize on new information about the improved immunogenicity. The specific aims of this proposal are: 1) To define precisely, by a combination of mutagenic and structural analyses, the conserved HIV-1 neutralization epitopes; 2) To examine the effect of removal of V1 and V2 variable loops on the immunogenicity of the HIV-1 envelope glycoproteins; and 3)To determine whether stabilization of particular native HIV-1 envelope glycoprotein structures improves immunogenicity.
Funding Period: 1991-07-15 - 2003-03-31
more information: NIH RePORT

Top Publications

  1. ncbi Analysis of the neutralizing antibody response elicited in rabbits by repeated inoculation with trimeric HIV-1 envelope glycoproteins
    Christoph Grundner
    Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Virology 331:33-46. 2005
  2. ncbi Inter-subunit disulfide bonds in soluble HIV-1 envelope glycoprotein trimers
    Wen Yuan
    Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Virology 332:369-83. 2005
  3. ncbi Stoichiometry of antibody neutralization of human immunodeficiency virus type 1
    Xinzhen Yang
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, JFB 609, 44 Binney St, Boston, MA 02115, USA
    J Virol 79:3500-8. 2005
  4. ncbi An unrelated monoclonal antibody neutralizes human immunodeficiency virus type 1 by binding to an artificial epitope engineered in a functionally neutral region of the viral envelope glycoproteins
    Xinping Ren
    Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA
    J Virol 79:5616-24. 2005
  5. ncbi Functional mimicry of a human immunodeficiency virus type 1 coreceptor by a neutralizing monoclonal antibody
    Shi Hua Xiang
    Jimmy Fund Building, Room 824, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    J Virol 79:6068-77. 2005
  6. ncbi Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1
    Xinzhen Yang
    Dana Farber Cancer Institute, Department of Cancer Immunology and AIDS, 44 Binney Street, JFB 824, Boston, MA 02115, USA
    J Virol 79:12132-47. 2005
  7. ncbi Structure of a V3-containing HIV-1 gp120 core
    Chih Chin Huang
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    Science 310:1025-8. 2005
  8. ncbi Adaptation of the human immunodeficiency virus type 1 envelope glycoproteins to new world monkey receptors
    Beatriz Pacheco
    Dana Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA
    J Virol 82:346-57. 2008
  9. ncbi Small-molecule CD4 mimics interact with a highly conserved pocket on HIV-1 gp120
    Navid Madani
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA
    Structure 16:1689-701. 2008

Scientific Experts

  • Xinzhen Yang
  • Joseph Sodroski
  • Shi Hua Xiang
  • Navid Madani
  • Chih Chin Huang
  • Richard Wyatt
  • Beatriz Pacheco
  • Peter D Kwong
  • Liping Wang
  • Shi-Hua Xiang
  • Christoph Grundner
  • Wen Yuan
  • Xinping Ren
  • Evan T Brower
  • Amos B Smith
  • Arne SchOn
  • Stephane Basmaciogullari
  • Joel R Courter
  • Ernesto Freire
  • Judith M LaLonde
  • Jason A LaBonte
  • Danny Ng
  • Takahiro Soeta
  • Amy M Princiotto
  • Young Do Kwon
  • Min Tang
  • Yuxing Li
  • Eric Rosenberg
  • Michael Farzan
  • Ian A Wilson
  • Mei Yun Zhang
  • Stewart Craig
  • John Mascola
  • Bette Korber
  • Zhihai Si
  • Shahzad Majeed
  • Robyn L Stanfield
  • Chih-chin Huang
  • Mei-Yun Zhang
  • Elizabeth Montabana
  • James Robinson
  • Dimiter S Dimitrov
  • Mark Louder

Detail Information

Publications9

  1. ncbi Analysis of the neutralizing antibody response elicited in rabbits by repeated inoculation with trimeric HIV-1 envelope glycoproteins
    Christoph Grundner
    Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Virology 331:33-46. 2005
    ....
  2. ncbi Inter-subunit disulfide bonds in soluble HIV-1 envelope glycoprotein trimers
    Wen Yuan
    Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA
    Virology 332:369-83. 2005
    ..These studies provide guidance in improving the resemblance of tractable, soluble forms of the HIV-1 envelope glycoproteins to the native virion spikes...
  3. ncbi Stoichiometry of antibody neutralization of human immunodeficiency virus type 1
    Xinzhen Yang
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, JFB 609, 44 Binney St, Boston, MA 02115, USA
    J Virol 79:3500-8. 2005
    ..Understanding these requirements for HIV-1 neutralization by antibodies will assist in establishing goals for an effective AIDS vaccine...
  4. ncbi An unrelated monoclonal antibody neutralizes human immunodeficiency virus type 1 by binding to an artificial epitope engineered in a functionally neutral region of the viral envelope glycoproteins
    Xinping Ren
    Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA
    J Virol 79:5616-24. 2005
    ..Thus, the specific target of a neutralizing antibody need not contribute functionally to the process of virus entry...
  5. ncbi Functional mimicry of a human immunodeficiency virus type 1 coreceptor by a neutralizing monoclonal antibody
    Shi Hua Xiang
    Jimmy Fund Building, Room 824, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    J Virol 79:6068-77. 2005
    ..Sulfation of N-terminal tyrosines contributed to the function of this chimeric receptor. These results emphasize the close mimicry of the CCR5 N terminus by the gp120-interactive region of a naturally elicited CD4i antibody...
  6. ncbi Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1
    Xinzhen Yang
    Dana Farber Cancer Institute, Department of Cancer Immunology and AIDS, 44 Binney Street, JFB 824, Boston, MA 02115, USA
    J Virol 79:12132-47. 2005
    ..The different entry requirements for cooperativity among Env trimers for retroviruses and influenza A virus may influence viral strategies for replication and evasion of the immune system...
  7. ncbi Structure of a V3-containing HIV-1 gp120 core
    Chih Chin Huang
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    Science 310:1025-8. 2005
    ..The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization...
  8. ncbi Adaptation of the human immunodeficiency virus type 1 envelope glycoproteins to new world monkey receptors
    Beatriz Pacheco
    Dana Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA
    J Virol 82:346-57. 2008
    ....
  9. ncbi Small-molecule CD4 mimics interact with a highly conserved pocket on HIV-1 gp120
    Navid Madani
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA
    Structure 16:1689-701. 2008
    ....