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Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies

Author

Listed:
  • Nicole A. Doria-Rose

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Chaim A. Schramm

    (Columbia University)

  • Jason Gorman

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Penny L. Moore

    (Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa
    Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa
    Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa)

  • Jinal N. Bhiman

    (Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa
    Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa)

  • Brandon J. DeKosky

    (University of Texas at Austin)

  • Michael J. Ernandes

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Ivelin S. Georgiev

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Helen J. Kim

    (The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute
    IAVI Neutralizing Antibody Center, The Scripps Research Institute)

  • Marie Pancera

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Ryan P. Staupe

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Han R. Altae-Tran

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Robert T. Bailer

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Ema T. Crooks

    (Torrey Pines Institute)

  • Albert Cupo

    (Weill Medical College of Cornell University)

  • Aliaksandr Druz

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Nigel J. Garrett

    (Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa)

  • Kam H. Hoi

    (University of Texas at Austin)

  • Rui Kong

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Mark K. Louder

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Nancy S. Longo

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Krisha McKee

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Molati Nonyane

    (Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa)

  • Sijy O’Dell

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Ryan S. Roark

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Rebecca S. Rudicell

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Stephen D. Schmidt

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Daniel J. Sheward

    (Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and NHLS, Cape Town 7701, South Africa)

  • Cinque Soto

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Constantinos Kurt Wibmer

    (Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa
    Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa)

  • Yongping Yang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Zhenhai Zhang

    (Columbia University)

  • James C. Mullikin

    (NISC Comparative Sequencing program, National Institutes of Health
    NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health)

  • James M. Binley

    (Torrey Pines Institute)

  • Rogier W. Sanders

    (Academic Medical Center, Amsterdam 1105 AZ, Netherlands)

  • Ian A. Wilson

    (The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute
    IAVI Neutralizing Antibody Center, The Scripps Research Institute
    Skaggs Institute for Chemical Biology, The Scripps Research Institute)

  • John P. Moore

    (Weill Medical College of Cornell University)

  • Andrew B. Ward

    (The Scripps Research Institute
    Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute
    IAVI Neutralizing Antibody Center, The Scripps Research Institute)

  • George Georgiou

    (University of Texas at Austin
    University of Texas at Austin
    University of Texas at Austin)

  • Carolyn Williamson

    (Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa
    Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and NHLS, Cape Town 7701, South Africa)

  • Salim S. Abdool Karim

    (Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa
    Columbia University)

  • Lynn Morris

    (Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, South Africa
    Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa
    Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa)

  • Peter D. Kwong

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Lawrence Shapiro

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
    Columbia University)

  • John R. Mascola

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

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.

Suggested Citation

  • Nicole A. Doria-Rose & Chaim A. Schramm & Jason Gorman & Penny L. Moore & Jinal N. Bhiman & Brandon J. DeKosky & Michael J. Ernandes & Ivelin S. Georgiev & Helen J. Kim & Marie Pancera & Ryan P. Staup, 2014. "Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies," Nature, Nature, vol. 509(7498), pages 55-62, May.
    • Handle: RePEc:nat:nature:v:509:y:2014:i:7498:d:10.1038_nature13036
    DOI: 10.1038/nature13036
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    Cited by:

    1. Svenja Weiss & Vincenza Itri & Ruimin Pan & Xunqing Jiang & Christina C. Luo & Lynn Morris & Delphine C. Malherbe & Philip Barnette & Jeff Alexander & Xiang-Peng Kong & Nancy L. Haigwood & Ann J. Hess, 2022. "Differential V2-directed antibody responses in non-human primates infected with SHIVs or immunized with diverse HIV vaccines," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Joana Dias & Giulia Fabozzi & Slim Fourati & Xuejun Chen & Cuiping Liu & David R. Ambrozak & Amy Ransier & Farida Laboune & Jianfei Hu & Wei Shi & Kylie March & Anna A. Maximova & Stephen D. Schmidt &, 2024. "Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIVAD8-EO infection," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Annemart Koornneef & Kanika Vanshylla & Gijs Hardenberg & Lucy Rutten & Nika M. Strokappe & Jeroen Tolboom & Jessica Vreugdenhil & Karin Feddes-de Boer & Aditya Perkasa & Sven Blokland & Judith A. Bur, 2024. "CoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Christoph Kreer & Cosimo Lupo & Meryem S. Ercanoglu & Lutz Gieselmann & Natanael Spisak & Jan Grossbach & Maike Schlotz & Philipp Schommers & Henning Gruell & Leona Dold & Andreas Beyer & Armita Nourm, 2023. "Probabilities of developing HIV-1 bNAb sequence features in uninfected and chronically infected individuals," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Kun-Wei Chan & Christina C. Luo & Hong Lu & Xueling Wu & Xiang-Peng Kong, 2021. "A site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    6. Bailey B. Banach & Sergei Pletnev & Adam S. Olia & Kai Xu & Baoshan Zhang & Reda Rawi & Tatsiana Bylund & Nicole A. Doria-Rose & Thuy Duong Nguyen & Ahmed S. Fahad & Myungjin Lee & Bob C. Lin & Tracy , 2023. "Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Jason Gorman & Crystal Sao-Fong Cheung & Zhijian Duan & Li Ou & Maple Wang & Xuejun Chen & Cheng Cheng & Andrea Biju & Yaping Sun & Pengfei Wang & Yongping Yang & Baoshan Zhang & Jeffrey C. Boyington , 2024. "Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    8. Li Chen & Mengmeng Sun & Huajun Zhang & Xinghai Zhang & Yanfeng Yao & Ming Li & Kangyin Li & Pengfei Fan & Haiwei Zhang & Ye Qin & Zhe Zhang & Entao Li & Zhen Chen & Wuxiang Guan & Shanshan Li & Chang, 2024. "Potent human neutralizing antibodies against Nipah virus derived from two ancestral antibody heavy chains," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

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