Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
29 05 2019
Historique:
received: 09 10 2018
accepted: 26 04 2019
entrez: 31 5 2019
pubmed: 31 5 2019
medline: 18 6 2019
Statut: epublish

Résumé

Stabilized HIV-1 envelope glycoproteins (Env) that resemble the native Env are utilized in vaccination strategies aimed at inducing broadly neutralizing antibodies (bNAbs). To limit the exposure of rare isolate-specific antigenic residues/determinants we generated a SOSIP trimer based on a consensus sequence of all HIV-1 group M isolates (ConM). The ConM trimer displays the epitopes of most known bNAbs and several germline bNAb precursors. The crystal structure of the ConM trimer at 3.9 Å resolution resembles that of the native Env trimer and its antigenic surface displays few rare residues. The ConM trimer elicits strong NAb responses against the autologous virus in rabbits and macaques that are significantly enhanced when it is presented on ferritin nanoparticles. The dominant NAb specificity is directed against an epitope at or close to the trimer apex. Immunogens based on consensus sequences might have utility in engineering vaccines against HIV-1 and other viruses.

Identifiants

pubmed: 31142746
doi: 10.1038/s41467-019-10262-5
pii: 10.1038/s41467-019-10262-5
pmc: PMC6541627
doi:

Substances chimiques

AIDS Vaccines 0
Antibodies, Neutralizing 0
Epitopes 0
HIV Antibodies 0
env Gene Products, Human Immunodeficiency Virus 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2355

Subventions

Organisme : NIAID NIH HHS
ID : P01 AI110657
Pays : United States
Organisme : NIAID NIH HHS
ID : UM1 AI100663
Pays : United States

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Auteurs

Kwinten Sliepen (K)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Byung Woo Han (BW)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA. bwhan@snu.ac.kr.
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Korea. bwhan@snu.ac.kr.

Ilja Bontjer (I)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Petra Mooij (P)

Department of Virology, Biomedical Primate Research Centre, 2280 GH, Rijswijk, The Netherlands.

Fernando Garces (F)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.
Department of Therapeutics Discovery, Amgen Research, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA, 91320, USA.

Anna-Janina Behrens (AJ)

Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
New England Biolabs Inc., 240 County Road, Ipswich, MA, 01938, USA.

Kimmo Rantalainen (K)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.

Sonu Kumar (S)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.

Anita Sarkar (A)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.

Philip J M Brouwer (PJM)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Yuanzi Hua (Y)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.

Monica Tolazzi (M)

Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy.

Edith Schermer (E)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Jonathan L Torres (JL)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.

Gabriel Ozorowski (G)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.

Patricia van der Woude (P)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Alba Torrents de la Peña (AT)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Mariëlle J van Breemen (MJ)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Juan Miguel Camacho-Sánchez (JM)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Judith A Burger (JA)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Max Medina-Ramírez (M)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Nuria González (N)

AIDS Immunopathology Unit, Instituto de Salud Carlos III, Madrid, 28220, Spain.

Jose Alcami (J)

AIDS Immunopathology Unit, Instituto de Salud Carlos III, Madrid, 28220, Spain.

Celia LaBranche (C)

Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA.

Gabriella Scarlatti (G)

Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy.

Marit J van Gils (MJ)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands.

Max Crispin (M)

Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK.
Centre for Biological Sciences and Institute for Life Sciences, University of Southampton, Southampton, SO17 1BJ, UK.

David C Montefiori (DC)

Department of Surgery, Duke University Medical Center, Durham, NC, 27710, USA.

Andrew B Ward (AB)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA.

Gerrit Koopman (G)

Department of Virology, Biomedical Primate Research Centre, 2280 GH, Rijswijk, The Netherlands.

John P Moore (JP)

Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, 10021, USA.

Robin J Shattock (RJ)

Section of Virology, Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London, W2 1PG, UK.

Willy M Bogers (WM)

Department of Virology, Biomedical Primate Research Centre, 2280 GH, Rijswijk, The Netherlands.

Ian A Wilson (IA)

Department of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA, 92037, USA. wilson@scripps.edu.
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA. wilson@scripps.edu.

Rogier W Sanders (RW)

Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam, 1105AZ, The Netherlands. r.w.sanders@amc.uva.nl.
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY, 10021, USA. r.w.sanders@amc.uva.nl.

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