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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors
Journal of Virology, Volume 85, No. 19, Year 2011
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Description
V2/V3 conformational epitope antibodies that broadly neutralize HIV-1 (PG9 and PG16) have been recently described. Since an elicitation of previously known broadly neutralizing antibodies has proven elusive, the induction of antibodies with such specificity is an important goal for HIV-1 vaccine development. A critical question is which immunogens and vaccine formulations might be used to trigger and drive the development of memory B cell precursors with V2/V3 conformational epitope specificity. In this paper we identified a clonal lineage of four V2/V3 conformational epitope broadly neutralizing antibodies (CH01 to CH04) from an African HIV-1-infected broad neutralizer and inferred their common reverted unmutated ancestor (RUA) antibodies. While conformational epitope antibodies rarely bind recombinant Env monomers, a screen of 32 recombinant envelopes for binding to the CH01 to CH04 antibodies showed monoclonal antibody (MAb) binding to the E.A244 gp120 Env and to chronic Env AE.CM243; MAbs CH01 and CH02 also bound to transmitted/founder Env B.9021. CH01 to CH04 neutralized 38% to 49% of a panel of 91 HIV-1 tier 2 pseudoviruses, while the RUAs neutralized only 16% of HIV-1 isolates. Although the reverted unmutated ancestors showed restricted neutralizing activity, they retained the ability to bind to the E.A244 gp120 HIV-1 envelope with an affinity predicted to trigger B cell development. Thus, E.A244, B.9021, and AE.CM243 Envs are three potential immunogen candidates for studies aimed at defining strategies to induce V2/V3 conformational epitope-specific antibodies. © 2011, American Society for Microbiology.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3196428/bin/supp_85_19_9998__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3196428/bin/supp_85_19_9998__1.pdf
Authors & Co-Authors
Bonsignori, Mattia
Unknown Affiliation
Hwang, Kwanki
Unknown Affiliation
Chen, Xi
Unknown Affiliation
Tsao, Chun Yen
Unknown Affiliation
Morris, Lynn
Unknown Affiliation
Gray, Elin Solomonovna
Unknown Affiliation
Marshall, Dawn Jones
Unknown Affiliation
Crump, John A.
Unknown Affiliation
Kapiga, Saidi Hussein
Unknown Affiliation
Sam, Noel E.
Unknown Affiliation
Sinangil, Faruk M.
Unknown Affiliation
Pancera, Marie
Unknown Affiliation
Yongping, Yang
Unknown Affiliation
Zhang, Baoshan
Unknown Affiliation
Zhu, Jiang
Unknown Affiliation
Kwong, Peter D.
Unknown Affiliation
O'Dell, Sijy J.
Unknown Affiliation
Mascola, John R.
Unknown Affiliation
Wu, Lan
Unknown Affiliation
Nabel, Gary J.
Unknown Affiliation
Phogat, Sanjay Kumar
Unknown Affiliation
Seaman, Michael S.
Unknown Affiliation
Whitesides, John F.
Unknown Affiliation
Moody, Michael Anthony
Unknown Affiliation
Kelsoe, Garnett H.
Unknown Affiliation
Yang, Xinzhen
Unknown Affiliation
Sodroski, Joseph G.
Unknown Affiliation
Shaw, George M.
Unknown Affiliation
Montefiori, David Charles
Unknown Affiliation
Kepler, Thomas B.
Unknown Affiliation
Tomaras, Georgia D.
Unknown Affiliation
Alam, S. Munir
Unknown Affiliation
Liao, Huaxin
Unknown Affiliation
Haynes, Barton F.
Unknown Affiliation
Statistics
Citations: 424
Authors: 34
Affiliations: 13
Identifiers
Doi:
10.1128/JVI.05045-11
ISSN:
0022538X
e-ISSN:
10985514
Research Areas
Infectious Diseases