Document Detail


Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target.
MedLine Citation:
PMID:  19729618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Broadly neutralizing antibodies (bNAbs), which develop over time in some HIV-1-infected individuals, define critical epitopes for HIV vaccine design. Using a systematic approach, we have examined neutralization breadth in the sera of about 1800 HIV-1-infected individuals, primarily infected with non-clade B viruses, and have selected donors for monoclonal antibody (mAb) generation. We then used a high-throughput neutralization screen of antibody-containing culture supernatants from about 30,000 activated memory B cells from a clade A-infected African donor to isolate two potent mAbs that target a broadly neutralizing epitope. This epitope is preferentially expressed on trimeric Envelope protein and spans conserved regions of variable loops of the gp120 subunit. The results provide a framework for the design of new vaccine candidates for the elicitation of bNAb responses.
Authors:
Laura M Walker; Sanjay K Phogat; Po-Ying Chan-Hui; Denise Wagner; Pham Phung; Julie L Goss; Terri Wrin; Melissa D Simek; Steven Fling; Jennifer L Mitcham; Jennifer K Lehrman; Frances H Priddy; Ole A Olsen; Steven M Frey; Phillip W Hammond; ; Stephen Kaminsky; Timothy Zamb; Matthew Moyle; Wayne C Koff; Pascal Poignard; Dennis R Burton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-03
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  326     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-09     Completed Date:  2009-10-19     Revised Date:  2012-04-25    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  285-9     Citation Subset:  IM    
Affiliation:
Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.
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MeSH Terms
Descriptor/Qualifier:
AIDS Vaccines / immunology*
Africa South of the Sahara
Antibodies, Monoclonal / immunology*
B-Lymphocyte Subsets / immunology
Epitopes / immunology
HIV Antibodies / biosynthesis,  immunology*
HIV Envelope Protein gp120 / chemistry,  immunology*
HIV Envelope Protein gp41 / immunology
HIV Infections / immunology*
HIV-1 / immunology*
Humans
Immunologic Memory
Lymphocyte Activation
Neutralization Tests
Peptide Fragments / immunology
Protein Multimerization
Recombinant Proteins / immunology
Grant Support
ID/Acronym/Agency:
AI33292/AI/NIAID NIH HHS; R01 AI033292-18/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/AIDS Vaccines; 0/Antibodies, Monoclonal; 0/Epitopes; 0/HIV Antibodies; 0/HIV Envelope Protein gp120; 0/HIV Envelope Protein gp41; 0/HIV envelope protein gp120 (305-321); 0/Peptide Fragments; 0/Recombinant Proteins; 0/gp120 protein, Human immunodeficiency virus 1; 0/gp41 protein, Human immunodeficiency virus 1
Investigator
Investigator/Affiliation:
G Miiro / ; J Serwanga / ; A Pozniak / ; D McPhee / ; O Manigart / ; L Mwananyanda / ; E Karita / ; A Inwoley / ; W Jaoko / ; J DeHovitz / ; L G Bekker / ; P Pitisuttithum / ; R Paris / ; S Allen /

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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