한빛사논문
- 조회2,118
Kwinten Sliepen1,15, Byung Woo Han2,3,16,*, Ilja Bontjer1,15, Petra Mooij4, Fernando Garce2,12, Anna-Janina Behrens5,13, Kimmo Rantalainen2, Sonu Kumar2, Anita Sarkar2, Philip J.M. Brouwer1, Yuanzi Hua2, Monica Tolazzi6, Edith Schermer1, Jonathan L. Torres2, Gabriel Ozorowski2, Patricia van der Woude1, Alba Torrents de la Peña1, Mariëlle J. van Breemen1, Juan Miguel Camacho-Sánchez1, Judith A. Burger1, Max Medina-Ramírez1, Nuria González7, Jose Alcami7, Celia LaBranche8, Gabriella Scarlatti6, Marit J. van Gils1, Max Crispin5,14, David C. Montefiori8, Andrew B. Ward2, Gerrit Koopman4, John P. Moore9, Robin J. Shattock10, Willy M. Bogers4, Ian A. Wilson2,11,16,* & Rogier W. Sanders1,9,16,*
1 Department of Medical Microbiology, Amsterdam Infection & Immunity Institute, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, Amsterdam 1105AZ, The Netherlands. 2 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. 3 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 08826, Korea. 4 Department of Virology, Biomedical Primate Research Centre, 2280 GH Rijswijk, The Netherlands. 5 Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. 6 Viral Evolution and Transmission Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan 20132, Italy. 7 AIDS Immunopathology Unit, Instituto de Salud Carlos III, Madrid 28220, Spain. 8 Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. 9 Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA. 10 Section of Virology, Division of Infectious Diseases, Department of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK. 11 The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 12Present address: Department of Therapeutics Discovery, Amgen Research, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, CA 91320, USA. 13 Present address: New England Biolabs Inc., 240 County Road, Ipswich, MA 01938, USA. 14 Present address: Centre for Biological Sciences and Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK. 15 These authors contributed equally: Kwinten Sliepen, Ilja Bontjer. 16These authors jointly supervised this work: Ian A. Wilson, Rogier W. Sanders, Byung Woo Han.
*Correspondence and requests for materials should be addressed to B.W.H. or to I.A.W. or to R.W.S.
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.
논문정보
- Research article
- 2019년 05월 (BRIC 등록일 2019-06-07)
- 국내(교신)+국외 연구진
- 생명과학 > 구조생물 및 생물물리학
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