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