Neutralizing antibody responses in acute HIV-1 subtype C infection The study of the evolution and specificities of neutralizing antibodies during the course of HIV-1 infection may be important in the discovery of possible targets for vaccine design. In this study we assessed the autologous and heterologous neutralization response in 14 HIV-1 subtype C infected individuals using envelope clones obtained within the first 2 months post-infection. Our data shows that potent, but relatively strain-specific, neutralizing antibodies develop within 3-12 months of HIV-1 infection. The magnitude of this response was associated with shorter envelope length and fewer glycosylation sites particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced epitopes developed to high titer in 12 participants and in most cases before autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificities conferred neutralization breadth, at least within the first year of infection. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection. Mapping the specificity of broadly neutralizing sera HIV-1 positive plasma samples obtained from the South Africa blood bank were used to determine whether neutralization breadth was associated with anti-CD4i or anti-MPER antibodies. The BED ELISA was performed to exclude samples from donors with recent infection which may confound the analysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI067854-04
Application #
7654141
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
4
Fiscal Year
2008
Total Cost
$1,780,229
Indirect Cost
Name
Duke University
Department
Type
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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