Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies

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. Staupe, Han R. Altae-Tran, Robert T. Bailer, Ema T. Crooks, Albert Cupo, Aliaksandr Druz, Nigel J. Garrett, Kam H. Hoi, Rui Kong, Mark K. Louder, Nancy S. Longo, Krisha McKee, Molati Nonyane, Sijy O’Dell, Ryan S. Roark, Rebecca S. Rudicell, Stephen D. Schmidt, Daniel J. Sheward, Cinque Soto, Constantinos Kurt Wibmer, Yongping Yang, Zhenhai Zhang, James C. Mullikin, James M. Binley, Rogier W. Sanders, Ian A. Wilson, John P. Moore, Andrew B. Ward, George Georgiou, Carolyn Williamson, Salim S. Abdool Karim, Lynn Morris (), Peter D. Kwong (), Lawrence Shapiro () and John R. Mascola ()
Additional contact information
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
Jinal N. Bhiman: Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, 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
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
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
James M. Binley: Torrey Pines Institute
Rogier W. Sanders: Academic Medical Center, Amsterdam 1105 AZ, Netherlands
Ian A. Wilson: The Scripps Research Institute
John P. Moore: Weill Medical College of Cornell University
Andrew B. Ward: The Scripps Research Institute
George Georgiou: 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
Salim S. Abdool Karim: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, 4013, South Africa
Lynn Morris: Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Johannesburg, 2131, 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
John R. Mascola: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health

Nature, 2014, vol. 509, issue 7498, 55-62

Abstract: 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.

Date: 2014
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DOI: 10.1038/nature13036

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