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Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.
Bradley, Todd; Fera, Daniela; Bhiman, Jinal; Eslamizar, Leila; Lu, Xiaozhi; Anasti, Kara; Zhang, Ruijung; Sutherland, Laura L; Scearce, Richard M; Bowman, Cindy M; Stolarchuk, Christina; Lloyd, Krissey E; Parks, Robert; Eaton, Amanda; Foulger, Andrew; Nie, Xiaoyan; Karim, Salim S Abdool; Barnett, Susan; Kelsoe, Garnett; Kepler, Thomas B; Alam, S Munir; Montefiori, David C; Moody, M Anthony; Liao, Hua-Xin; Morris, Lynn; Santra, Sampa; Harrison, Stephen C; Haynes, Barton F.
Afiliação
  • Bradley T; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: todd.bradley@duke.edu.
  • Fera D; Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Bhiman J; National Institute for Communicable Diseases, Johannesburg 2131, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2131, South Africa.
  • Eslamizar L; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • Lu X; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Anasti K; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Zhang R; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Sutherland LL; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Scearce RM; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Bowman CM; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Stolarchuk C; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Lloyd KE; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Parks R; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Eaton A; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Foulger A; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Nie X; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Karim SSA; Center for AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa; Columbia University, New York, NY 10032, USA.
  • Barnett S; Novartis Vaccines and Diagnostics, Inc., Cambridge, MA 02139, USA.
  • Kelsoe G; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Kepler TB; Boston University, Boston, MA 02118, USA.
  • Alam SM; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Montefiori DC; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Moody MA; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Liao HX; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Morris L; National Institute for Communicable Diseases, Johannesburg 2131, South Africa; Center for AIDS Program of Research in South Africa, University of KwaZulu-Natal, Durban 4013, South Africa; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2131, South Africa.
  • Santra S; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
  • Harrison SC; Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA.
  • Haynes BF; Duke Human Vaccine Institute, Departments of Medicine, Surgery and Immunology, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@duke.edu.
Cell Rep ; 14(1): 43-54, 2016 Jan 05.
Article em En | MEDLINE | ID: mdl-26725118
ABSTRACT
Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / HIV-1 / Vacinas contra a AIDS / Produtos do Gene env do Vírus da Imunodeficiência Humana / Anticorpos Neutralizantes Idioma: En Ano de publicação: 2016 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Anticorpos Anti-HIV / HIV-1 / Vacinas contra a AIDS / Produtos do Gene env do Vírus da Imunodeficiência Humana / Anticorpos Neutralizantes Idioma: En Ano de publicação: 2016 Tipo de documento: Article