Publication Date:
2009-09-05
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335270/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335270/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walker, Laura M -- Phogat, Sanjay K -- Chan-Hui, Po-Ying -- Wagner, Denise -- Phung, Pham -- Goss, Julie L -- Wrin, Terri -- Simek, Melissa D -- Fling, Steven -- Mitcham, Jennifer L -- Lehrman, Jennifer K -- Priddy, Frances H -- Olsen, Ole A -- Frey, Steven M -- Hammond, Phillip W -- Protocol G Principal Investigators -- Kaminsky, Stephen -- Zamb, Timothy -- Moyle, Matthew -- Koff, Wayne C -- Poignard, Pascal -- Burton, Dennis R -- AI33292/AI/NIAID NIH HHS/ -- MC_U950097145/Medical Research Council/United Kingdom -- R01 AI033292/AI/NIAID NIH HHS/ -- R01 AI033292-18/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2009 Oct 9;326(5950):285-9. doi: 10.1126/science.1178746. Epub 2009 Sep 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19729618" target="_blank"〉PubMed〈/a〉
Keywords:
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
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
