Publication Date:
2014-12-17
Description:
Some HIV-infected individuals develop broadly neutralizing antibodies (bNAbs), whereas most develop antibodies that neutralize only a narrow range of viruses (nNAbs). bNAbs, but not nNAbs, protect animals from experimental infection and are likely a key component of an effective vaccine. nNAbs and bNAbs target the same regions of the viral envelope glycoprotein (Env), but for reasons that remain unclear only nNAbs are elicited by Env immunization. We show that in contrast to germline-reverted (gl) bNAbs, glnNAbs recognized diverse recombinant Envs. Moreover, owing to binding affinity differences, nNAb B cell progenitors had an advantage in becoming activated and internalizing Env compared with bNAb B cell progenitors. We then identified an Env modification strategy that minimized the activation of nNAb B cells targeting epitopes that overlap those of bNAbs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290850/" 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/PMC4290850/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McGuire, Andrew T -- Dreyer, Anita M -- Carbonetti, Sara -- Lippy, Adriana -- Glenn, Jolene -- Scheid, Johannes F -- Mouquet, Hugo -- Stamatatos, Leonidas -- P01 AI094419/AI/NIAID NIH HHS/ -- P01 AI094419-01/AI/NIAID NIH HHS/ -- U19 19AI109632-01/AI/NIAID NIH HHS/ -- U19 AI109632/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2014 Dec 12;346(6215):1380-3. doi: 10.1126/science.1259206.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Seattle Biomedical Research Institute, Seattle, WA 98109, USA. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. ; Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur and CNRS-URA 1961, 75015 Paris, France. ; Seattle Biomedical Research Institute, Seattle, WA 98109, USA. Department of Global Health, University of Washington, Seattle, WA 98109, USA. lstamata@fhcrc.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25504724" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/immunology
;
Antibodies, Neutralizing/*immunology
;
Antibody Affinity
;
B-Lymphocytes/immunology
;
Binding, Competitive
;
Epitopes/immunology
;
HIV Antibodies/genetics/*immunology
;
HIV-1/*immunology
;
Humans
;
Lymphocyte Activation
;
Models, Molecular
;
Receptors, Antigen, B-Cell/genetics/immunology
;
Recombinant Proteins/immunology
;
env Gene Products, Human Immunodeficiency Virus/chemistry/genetics/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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