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

Kwinten Sliepen, Byung Woo Han (), Ilja Bontjer, Petra Mooij, Fernando Garces, Anna-Janina Behrens, Kimmo Rantalainen, Sonu Kumar, Anita Sarkar, Philip J. M. Brouwer, Yuanzi Hua, Monica Tolazzi, Edith Schermer, Jonathan L. Torres, Gabriel Ozorowski, Patricia Woude, Alba Torrents Peña, Mariëlle J. Breemen, Juan Miguel Camacho-Sánchez, Judith A. Burger, Max Medina-Ramírez, Nuria González, Jose Alcami, Celia LaBranche, Gabriella Scarlatti, Marit J. Gils, Max Crispin, David C. Montefiori, Andrew B. Ward, Gerrit Koopman, John P. Moore, Robin J. Shattock, Willy M. Bogers, Ian A. Wilson () and Rogier W. Sanders ()
Additional contact information
Kwinten Sliepen: University of Amsterdam
Byung Woo Han: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Ilja Bontjer: University of Amsterdam
Petra Mooij: Biomedical Primate Research Centre
Fernando Garces: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Anna-Janina Behrens: University of Oxford
Kimmo Rantalainen: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Sonu Kumar: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Anita Sarkar: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Philip J. M. Brouwer: University of Amsterdam
Yuanzi Hua: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Monica Tolazzi: IRCCS San Raffaele Scientific Institute
Edith Schermer: University of Amsterdam
Jonathan L. Torres: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Gabriel Ozorowski: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Patricia Woude: University of Amsterdam
Alba Torrents Peña: University of Amsterdam
Mariëlle J. Breemen: University of Amsterdam
Juan Miguel Camacho-Sánchez: University of Amsterdam
Judith A. Burger: University of Amsterdam
Max Medina-Ramírez: University of Amsterdam
Nuria González: Instituto de Salud Carlos III
Jose Alcami: Instituto de Salud Carlos III
Celia LaBranche: Duke University Medical Center
Gabriella Scarlatti: IRCCS San Raffaele Scientific Institute
Marit J. Gils: University of Amsterdam
Max Crispin: University of Oxford
David C. Montefiori: Duke University Medical Center
Andrew B. Ward: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Gerrit Koopman: Biomedical Primate Research Centre
John P. Moore: Weill Medical College of Cornell University
Robin J. Shattock: Imperial College London
Willy M. Bogers: Biomedical Primate Research Centre
Ian A. Wilson: Scripps CHAVI-ID, IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute
Rogier W. Sanders: University of Amsterdam

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-10262-5

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