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

Sliepen, Kwinten; Han, Byung Woo; Bontjer, Ilja; Mooij, Petra; Garces, Fernando; Behrens, Anna-Janina; Rantalainen, Kimmo; Kumar, Sonu; Sarkar, Anita; Brouwer, Philip J.  M.; Hua, Yuanzi; Tolazzi, Monica; Schermer, Edith; Torres, Jonathan L.; Ozorowski, Gabriel; van der Woude, Patricia; de la Peña, Alba Torrents; van Breemen, Mariëlle J.; Camacho-Sánchez, Juan Miguel; Burger, Judith A.; Medina-Ramírez, Max; González, Nuria; Alcami, Jose; LaBranche, Celia; Scarlatti, Gabriella; van Gils, Marit J.; Crispin, Max; Montefiori, David C.; Ward, Andrew B.; Koopman, Gerrit; Moore, John P.; Shattock, Robin J.; Bogers, Willy M.; Wilson, Ian A.; Sanders, Rogier W.

doi:10.1038/s41467-019-10262-5

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

Journal Article · Wed May 29 00:00:00 EDT 2019 · Nature Communications

DOI:https://doi.org/10.1038/s41467-019-10262-5· OSTI ID:1624156

^[1];

^[2]; Bontjer, Ilja ^[3]; Mooij, Petra ^[4]; Garces, Fernando ^[5]; Behrens, Anna-Janina ^[6]; Rantalainen, Kimmo ^[7];

^[7];

^[7]; Brouwer, Philip J. M. ^[3]; Hua, Yuanzi ^[8]; Tolazzi, Monica ^[9]; Schermer, Edith ^[3];

^[8];

^[8]; van der Woude, Patricia ^[3]; de la Peña, Alba Torrents ^[3]; van Breemen, Mariëlle J. ^[3];

^[3]; Burger, Judith A. ^[3] more »

Univ. of Amsterdam (Netherlands). Dept. of Medical Microbiology, Amsterdam Infection & Immunity Institute
The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD); Seoul National Univ. (Korea, Republic of). Research Institute of Pharmaceutical Sciences, College of Pharmacy
Univ. of Amsterdam (Netherlands). Dept. of Medical Microbiology, Amsterdam Infection & Immunity Institute
Biomedical Primate Research Centre, Rijswijk (Netherlands). Dept. of Virology
The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD); Amgen Inc., Thousand Oaks, CA (United States). Dept. of Therapeutics Discovery
Univ. of Oxford (United Kingdom). Oxford Glycobiology Institute, Department of Biochemistry; New England Biolabs Inc., Ipswich, MA (United States)
The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD)
The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD)
IRCCS San Raffaele Scientific Institute, Milan (Italy). Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases
Carlos III Health Inst., Madrid (Spain). AIDS Immunopathology Unit
Duke Univ., Durham, NC (United States). Medical Center, Dept. of Surgery
IRCCS San Raffaele Scientific Institute, Milan (Italy). Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases
Univ. of Oxford (United Kingdom). Dept. of Biochemistry, Oxford Glycobiology Institute; Univ. of Southampton (United Kingdom). Centre for Biological Sciences and Inst. for Life Sciences
Cornell Univ., Ithaca, NY (United States). Weill Medical College, Dept. of Microbiology and Immunology
Imperial College, London (United Kingdom). Section of Virology, Division of Infectious Diseases, Dept. of Medicine
Biomedical Primate Research Centre, Rijswijk (Netherlands). Dept. of Virology
The Scripps Research Insttute, La Jolla, CA (United States). Dept. of Integrative Structural and Computational Biology, Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD); Scripps Research Institute, San Diego, CA (United States). Skaggs Inst. for Chemical Biology
Univ. of Amsterdam (Netherlands). Dept. of Medical Microbiology, Amsterdam Infection & Immunity Institute; Cornell Univ., Ithaca, NY (United States). Weill Medical College, Dept. of Microbiology and Immunology

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 3.9Å 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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); European Research Council (ERC); National Institutes of Health (NIH); Bill and Melinda Gates Foundation; National Research Foundation of Korea (NRF)

Grant/Contract Number:: AC02-06CH11357; 681137; P01 AI110657; HHSN27201100016C; OPP1111923; OPP1132237; OPP1115782; NRF-2013M-3A6A-4043695; 2011–0030001; Y1-CO-1020; Y1-GM-1104

OSTI ID:: 1624156

Journal Information:: Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Alphaherpesvirinae and Gammaherpesvirinae glycoprotein L and CMV UL130 originate from chemokines Malkowska, Maja; Kokoszynska, Katarzyna; Dymecka, Magdalena Virology Journal, Vol. 10, Issue 1 https://doi.org/10.1186/1743-422x-10-1	journal	January 2013

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Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements Henderson, Rory; Lu, Maolin; Zhou, Ye Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-019-14196-w	journal	January 2020
Strategies for inducing effective neutralizing antibody responses against HIV-1 del Moral-Sánchez, Iván; Sliepen, Kwinten Expert Review of Vaccines, Vol. 18, Issue 11 https://doi.org/10.1080/14760584.2019.1690458	journal	November 2019
Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies Brinkkemper, Mitch; Sliepen, Kwinten Vaccines, Vol. 7, Issue 3 https://doi.org/10.3390/vaccines7030076	journal	July 2019
Viral Vectors for the Induction of Broadly Neutralizing Antibodies against HIV Wilmschen, Sarah; Schmitz, Joern E.; Kimpel, Janine Vaccines, Vol. 7, Issue 3 https://doi.org/10.3390/vaccines7030119	journal	September 2019
Stabilized diverse HIV-1 envelope trimers for vaccine design Wang, Qian; Ma, Bingting; Liang, Qingtai Taylor & Francis https://doi.org/10.6084/m9.figshare.12091959	text	January 2020
HIV-1 Envelope and MPER Antibody Structures in Lipid Assemblies Rantalainen, Kimmo; Berndsen, Zachary T.; Antanasijevic, Aleksandar Cell Reports, Vol. 31, Issue 4 https://doi.org/10.1016/j.celrep.2020.107583	journal	April 2020
Stabilized diverse HIV-1 envelope trimers for vaccine design Wang, Qian; Ma, Bingting; Liang, Qingtai Emerging Microbes & Infections, Vol. 9, Issue 1 https://doi.org/10.1080/22221751.2020.1745093	journal	January 2020
V2-Specific Antibodies in HIV-1 Vaccine Research and Natural Infection: Controllers or Surrogate Markers Duerr, Ralf; Gorny, Miroslaw K. Vaccines, Vol. 7, Issue 3 https://doi.org/10.3390/vaccines7030082	journal	August 2019

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