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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Characterizing anti-HIV monoclonal antibodies and immune sera by defining the mechanism of neutralization
Human Antibodies, Volume 14, No. 3-4, Year 2005
Notification
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Description
Understanding the nature of neutralization may provide information for crafting improvements in HIV vaccines. Using JR-FL as a prototype primary pseudovirus, we first investigated anti-HIV monoclonal antibodies (mAbs) in several neutralization formats designed to elucidate the timing of neutralization. MAb b12 was most effective before receptor binding, 2G12 neutralized effectively even after CD4 binding, and X5 and a V3 loop mAb (LE311) were inactive in a standard format but were induced by sCD4. Consistent with this latter finding, native PAGE indicated that X5 and V3 mAb binding to Envelope trimers was dependent on sCD4 binding. In contrast, 2F5 and 4E10 were active even post-CD4/CCR5 engagement. We next analyzed the neutralization mechanism of a panel of HIV+ donor plasmas of various potencies. All mediated high levels of post-CD4 neutralization that was not associated with activity in the standard format. None, however, neutralized effectively in the post-CD4/CCR5 format, suggesting that 2F5/4E10-like Abs were absent or at low concentrations. Finally, we analyzed a non-neutralizing plasma spiked with mAbs b12, 2G12 or 2F5, which resulted in increases in neutralization titers consistent with the activities of the mAbs. We conclude that these methods, together with other mapping approaches, may provide a better understanding of neutralization that could be useful in vaccine research. © 2005 - IOS Press and the authors. All rights reserved.
Authors & Co-Authors
Crooks, Emma T.
United States, San Diego
Torrey Pines Institute for Molecular Studies
Moore, Penny L.
United States, San Diego
Torrey Pines Institute for Molecular Studies
South Africa, Johannesburg
National Institute for Communicable Diseases
Richman, Douglas D.
United States, La Jolla
University of California, San Diego
Robinson, James E.
United States, New Orleans
Tulane Medical Center
Crooks, Jeffrey A.
United States, Washington, D.c.
National Oceanic and Atmospheric Administration
Franti, Michael
United States, Bedford
Lantheus
Schülke, Norbert
United States, Cambridge
Takeda Oncology
Binley, James M.
United States, San Diego
Torrey Pines Institute for Molecular Studies
Statistics
Citations: 64
Authors: 8
Affiliations: 7
Identifiers
Doi:
10.3233/hab-2005-143-407
ISSN:
10932607
Research Areas
Infectious Diseases