Recent data indicate that the V1/V2 domain of HIV-1 gp120 is an important target for viral neutralization, particularly for primary viral isolates. To allow the characterization of epitopes expressed in native V1/V2 domains, the principal investigator has developed and applied a glycoprotein expression system which produces correctly folded V1/V2 regions as fusion glycoproteins. Using this system he has recently found that, in spite of the relative variability of the V1/V2 domain, the sera of some humans infected with HIV-1 possess broadly crossreacting anti- V1/V2 antibodies, including antibodies that recognize the V1/V2 domains from multiple clades. Certain fractions of these antibodies possess potent neutralization activity for primary, macrophage-tropic isolates, while other fractions do not. The goal of the present application is to examine additional human sera for the presence of anti-V1/V2 antibodies that mediate potent neutralization of primary viruses, explore the nature of the epitopes involved, define the breadth of expression of these epitopes in clade B isolates and isolates from other clades, purify and characterize human polyclonal and monoclonal antibodies against these eptiopes and determine their mechanism of neutralization. He will also examine the ability of HIV to escape neutralization by such antibodies and characterize the structure of the escape mutants. The long term goal of these studies is to learn enough about this domain to allow the design of an effective vaccine capable of inducing potent and broadly crossreacting anti-V1/V2 antibodies that may provide broad protection against infection and that may be of therapeutic value in already infected individuals who may not otherwise possess such antibodies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI034217-06
Application #
2672221
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Project Start
1993-07-01
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
6
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Public Health Research Institute
Department
Type
DUNS #
City
Newark
State
NJ
Country
United States
Zip Code
07103
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Kayman, S C; Wu, Z; Revesz, K et al. (1994) Presentation of native epitopes in the V1/V2 and V3 regions of human immunodeficiency virus type 1 gp120 by fusion glycoproteins containing isolated gp120 domains. J Virol 68:400-10