Publication Date:
2015-06-20
Description:
A major goal of HIV-1 vaccine research is the design of immunogens capable of inducing broadly neutralizing antibodies (bnAbs) that bind to the viral envelope glycoprotein (Env). Poor binding of Env to unmutated precursors of bnAbs, including those of the VRC01 class, appears to be a major problem for bnAb induction. We engineered an immunogen that binds to VRC01-class bnAb precursors and immunized knock-in mice expressing germline-reverted VRC01 heavy chains. Induced antibodies showed characteristics of VRC01-class bnAbs, including a short CDRL3 (light-chain complementarity-determining region 3) and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate VRC01-class precursors. The results suggest that rational epitope design can prime rare B cell precursors for affinity maturation to desired targets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669217/" 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/PMC4669217/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jardine, Joseph G -- Ota, Takayuki -- Sok, Devin -- Pauthner, Matthias -- Kulp, Daniel W -- Kalyuzhniy, Oleksandr -- Skog, Patrick D -- Thinnes, Theresa C -- Bhullar, Deepika -- Briney, Bryan -- Menis, Sergey -- Jones, Meaghan -- Kubitz, Mike -- Spencer, Skye -- Adachi, Yumiko -- Burton, Dennis R -- Schief, William R -- Nemazee, David -- 1UM1AI100663/AI/NIAID NIH HHS/ -- P01 AI094419/AI/NIAID NIH HHS/ -- P01AI081625/AI/NIAID NIH HHS/ -- R01 AI073148/AI/NIAID NIH HHS/ -- R01 AI081625/AI/NIAID NIH HHS/ -- R01-AI073148/AI/NIAID NIH HHS/ -- T32 AI007244/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2015 Jul 10;349(6244):156-61. doi: 10.1126/science.aac5894. Epub 2015 Jun 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center (NAC), The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center (NAC), The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. nemazee@scripps.edu schief@scripps.edu burton@scripps.edu. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. nemazee@scripps.edu schief@scripps.edu burton@scripps.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26089355" target="_blank"〉PubMed〈/a〉
Keywords:
AIDS Vaccines/*immunology
;
Animals
;
Antibodies, Monoclonal/biosynthesis/*immunology
;
Antibodies, Neutralizing/biosynthesis/*immunology
;
Antibody Affinity
;
B-Lymphocytes/immunology
;
Complementarity Determining Regions/genetics/immunology
;
Epitopes/genetics/immunology
;
HIV Antibodies/biosynthesis/*immunology
;
HIV Envelope Protein gp120/genetics/*immunology
;
HIV Infections/*prevention & control
;
HIV-1/*immunology
;
Immunoglobulin Heavy Chains/genetics/immunology
;
Mice
;
Mice, Knockout
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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