Format

Send to

Choose Destination
See comment in PubMed Commons below
Nature. 2014 May 1;509(7498):55-62. doi: 10.1038/nature13036. Epub 2014 Mar 2.

Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.

Author information

1
1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2].
2
1] Department of Biochemistry, Columbia University, New York, New York 10032, USA [2].
3
1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [4].
4
1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa.
5
Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA.
6
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
7
1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [3] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA.
8
Torrey Pines Institute, San Diego, California 92037, USA.
9
Weill Medical College of Cornell University, New York, New York 10065, USA.
10
Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa.
11
Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA.
12
Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa.
13
Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town and NHLS, Cape Town 7701, South Africa.
14
Department of Biochemistry, Columbia University, New York, New York 10032, USA.
15
1] NISC Comparative Sequencing program, National Institutes of Health, Bethesda, Maryland 20892, USA [2] NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
16
Department of Medical Microbiology, Academic Medical Center, Amsterdam 1105 AZ, Netherlands.
17
1] Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, California 92037, USA [2] Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California 92037, USA [3] IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California 92037, USA [4] Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
18
1] Department of Chemical Engineering, University of Texas at Austin, Austin, Texas 78712, USA [2] Department of Biomedical Engineering, University of Texas at Austin, Austin, Texas, USA [3] Department of Molecular Biosciences, University of Texas at Austin, Austin, Texas 78712, USA.
19
1] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [2] Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, University of Cape Town and NHLS, Cape Town 7701, South Africa.
20
1] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa [2] Department of Epidemiology, Columbia University, New York, New York 10032, USA.
21
1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa [2] Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa.
22
1] Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA [2] Department of Biochemistry, Columbia University, New York, New York 10032, USA.

Abstract

Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by which such antibodies are generated and acquire the requisite molecular characteristics for neutralization. Twelve somatically related neutralizing antibodies (CAP256-VRC26.01-12) were isolated from donor CAP256 (from the Centre for the AIDS Programme of Research in South Africa (CAPRISA)); each antibody contained the protruding tyrosine-sulphated, anionic antigen-binding loop (complementarity-determining region (CDR) H3) characteristic of this category of antibodies. Their unmutated ancestor emerged between weeks 30-38 post-infection with a 35-residue CDR H3, and neutralized the virus that superinfected this individual 15 weeks after initial infection. Improved neutralization breadth and potency occurred by week 59 with modest affinity maturation, and was preceded by extensive diversification of the virus population. HIV-1 V1V2-directed neutralizing antibodies can thus develop relatively rapidly through initial selection of B cells with a long CDR H3, and limited subsequent somatic hypermutation. These data provide important insights relevant to HIV-1 vaccine development.

PMID:
24590074
PMCID:
PMC4395007
DOI:
10.1038/nature13036
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source IDs, Grant support

Publication types

MeSH terms

Substances

Secondary source IDs

Grant support

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center