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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination
Virology, Volume 387, No. 2, Year 2009
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Description
Identifying the earliest neutralizing antibody specificities that are elicited following infection or vaccination by HIV-1 is an important objective of current HIV/AIDS vaccine research. We have shown previously that transplantation of HIV-1 V3 epitopes into an HIV-2 envelope (Env) scaffold provides a sensitive and specific means to detect and quantify HIV-1 V3 epitope specific neutralizing antibodies (Nabs) in human sera. Here, we employ this HIV-2/HIV-1 V3 scaffolding strategy to study the kinetics of development and breadth of V3-specific Nabs in longitudinal sera from individuals acutely infected with clade C or clade B HIV-1 and in human subjects immunized with clade B HIV-1 immunogens. HIV-2/HIV-1 chimeras containing V3 sequences matched to virus type (HIV-2 or HIV-1), subtype (clade B or C), or strain (autologous or heterologous) were used as test reagents. We found that by 3-8 weeks post infection, 12 of 14 clade C subjects had a median IC50 V3-specific Nab titer of 1:700 against chimeric viruses containing a heterologous clade C V3. By 5 months post-infection, all 14 subjects were positive for V3-specific Nabs with median titers of 1:8000 against heterologous clade C V3 and 1:1300 against clade B V3. Two acutely infected clade B patients developed heterologous clade B V3-specific Nabs at titers of 1:300 and 1:1800 by 13 weeks of infection and 1:5000 and 1:11000 by 7 months of infection. Titers were not different against chimeras containing autologous clade B V3 sequences. Each of 10 uninfected normal human volunteers who were immunized with clade B HIV-1 Env immunogens, but none of five sham immunized control subjects, developed V3-specific Nabs titers as high as 1:3000 (median 1:1300; range 1:700-1:3000). None of the HIV-1 infected or vaccinated subjects had antibodies that neutralized primary HIV-1 virus strains. These results indicate that high-titer, broadly reactive V3-specific antibodies are among the first to be elicited during acute and early HIV-1 infection and following vaccination but these antibodies lack neutralizing potency against primary HIV-1 viruses, which effectively shield V3 from antibody binding to the functional Env trimer. © 2009 Elsevier Inc.
Authors & Co-Authors
Davis, Katie L.
United States, Birmingham
The University of Alabama at Birmingham
Gray, Elin Solomonovna
South Africa, Johannesburg
National Institute for Communicable Diseases
Moore, Penny L.
South Africa, Johannesburg
National Institute for Communicable Diseases
Decker, Julie M.
United States, Birmingham
The University of Alabama at Birmingham
Salomon, Aidy
United States, Newark
Public Health Research Institute
United States, Newark
Rutgers new Jersey Medical School
Montefiori, David Charles
United States, Durham
Duke University Medical Center
Graham, Barney S.
United States, Bethesda
National Institute of Allergy and Infectious Diseases Niaid
Keefer, Michael C.
United States, Rochester
University of Rochester School of Medicine and Dentistry
Pinter, Abraham
United States, Newark
Public Health Research Institute
United States, Newark
Rutgers new Jersey Medical School
Morris, Lynn
South Africa, Johannesburg
National Institute for Communicable Diseases
Hahn, Beatrice H.
United States, Birmingham
The University of Alabama at Birmingham
Shaw, George M.
United States, Birmingham
The University of Alabama at Birmingham
Statistics
Citations: 105
Authors: 12
Affiliations: 7
Identifiers
Doi:
10.1016/j.virol.2009.02.022
ISSN:
00426822
e-ISSN:
10960341
Research Areas
Infectious Diseases
Study Design
Cohort Study