The goal of this project is to understand how HIV-1 in neutralized by antibodies to its envelope glycoproteins and how primary viruses resist these antibodies. Understanding the neutralizing antibody response to HIV-1 infection is relevant to a full comprehension of viral pathogenesis, and is of particular importance to the rational development of HIV-1 vaccines based, at least in part, on the induction of humoral immunity. In principle, the binding of neutralizing antibodies to HIV virions will reduce their infectivity for CD4+ target cells. However, despite an extremely vigorous antibody response to its envelope glycoproteins, HIV neutralization titers during natural infection are generally weak. Furthermore, no experimental vaccine has yet induced strong, cross-neutralizing antibodies active against primary viruses. We believe that resistance mechanisms evolved by HIV-1 to counter neutralizing antibodies contribute significantly to this problem. During the first four years of this grant, the PI's group helped to characterize and understand these resistance mechanisms. To continue and extend this work he proposed in the 1st Specific Aim to refine and use novel assays of HIV-1 INTERACTIONS WITH cd4+ target cells, and to determine how inhibition of virus binding correlates with neutralization of infectivity. The role of the co-receptors CCR5 and CXCR4 in the neutralization of HIV-1 binding and entry will also be studied. In the second specific aim, he will asses the influence of viral phenotype (co-receptor usage) on the sensitivity of primary HIV-1 isolates to neutralizing antibodies.
His third aim i s to develop new assays for HIV-1 neutralization based on co-receptor transfected cells engineered to express reporter genes such as beta- galactosidase, luciferase and green fluorescent protein, then to use these assays to re-assess the capacity of serum antibodies to neutralize HIV-1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI036082-07
Application #
6149796
Study Section
AIDS and Related Research Study Section 1 (ARRA)
Program Officer
Bradac, James A
Project Start
1994-05-01
Project End
2000-04-30
Budget Start
2000-02-01
Budget End
2000-04-30
Support Year
7
Fiscal Year
2000
Total Cost
$145,762
Indirect Cost
Name
Aaron Diamond AIDS Research Center
Department
Type
DUNS #
786658872
City
New York
State
NY
Country
United States
Zip Code
10016
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Behrens, Anna-Janina; Vasiljevic, Snezana; Pritchard, Laura K et al. (2016) Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein. Cell Rep 14:2695-706
Klasse, P J; LaBranche, Celia C; Ketas, Thomas J et al. (2016) Sequential and Simultaneous Immunization of Rabbits with HIV-1 Envelope Glycoprotein SOSIP.664 Trimers from Clades A, B and C. PLoS Pathog 12:e1005864

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