V1/V2 DOMAIN OF GP120 AND NEUTRALIZATION OF HIV-1

Project Details

Description

DESCRIPTION: 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.
StatusFinished
Effective start/end date7/1/936/30/00

Funding

  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases
  • National Institute of Allergy and Infectious Diseases

ASJC

  • Virology
  • Immunology

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