The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template
Raiees Andrabi,
Jesper Pallesen,
Joel D. Allen,
Ge Song,
Jinsong Zhang,
Natalia de Val,
Gavin Gegg,
Katelyn Porter,
Ching-Yao Su,
Matthias Pauthner,
Amanda Newman,
Hilary Bouton-Verville,
Fernando Garces,
Ian A. Wilson,
Max Crispin,
Beatrice H. Hahn,
Barton F. Haynes,
Laurent Verkoczy,
Andrew B. Ward,
Dennis R. Burton
Affiliations
Raiees Andrabi
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA
Jesper Pallesen
International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Joel D. Allen
International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; School of Biological Sciences, University of Southampton, Southampton, UK
Ge Song
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA
Jinsong Zhang
Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
Natalia de Val
International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Gavin Gegg
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA
Katelyn Porter
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA
Ching-Yao Su
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA
Matthias Pauthner
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA
Amanda Newman
Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
Hilary Bouton-Verville
Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA
Fernando Garces
International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Ian A. Wilson
International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
Max Crispin
International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; School of Biological Sciences, University of Southampton, Southampton, UK
Beatrice H. Hahn
Departments of Medicine and Microbiology, University of Pennsylvania, Philadelphia, PA 19104, USA
Barton F. Haynes
Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Immunology, Duke University School of Medicine, Durham, NC 27710, USA
Laurent Verkoczy
Duke Human Vaccine Institute and Departments of Medicine and Immunology, Duke University School of Medicine, Durham, NC 27710, USA; Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA; San Diego Biomedical Research Institute, San Diego, CA 92121, USA
Andrew B. Ward
International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; Corresponding author
Dennis R. Burton
Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; International AIDS Vaccine Initiative, Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02114, USA; Corresponding author
Summary: Epitope-targeted HIV vaccine design seeks to focus antibody responses to broadly neutralizing antibody (bnAb) sites by sequential immunization. A chimpanzee simian immunodeficiency virus (SIV) envelope (Env) shares a single bnAb site, the variable loop 2 (V2)-apex, with HIV, suggesting its possible utility in an HIV immunization strategy. Here, we generate a chimpanzee SIV Env trimer, MT145K, which displays selective binding to HIV V2-apex bnAbs and precursor versions, but no binding to other HIV specificities. We determine the structure of the MT145K trimer by cryo-EM and show that its architecture is remarkably similar to HIV Env. Immunization of an HIV V2-apex bnAb precursor Ab-expressing knockin mouse with the chimpanzee MT145K trimer induces HIV V2-specific neutralizing responses. Subsequent boosting with an HIV trimer cocktail induces responses that exhibit some virus cross-neutralization. Overall, the chimpanzee MT145K trimer behaves as expected from design both in vitro and in vivo and is an attractive potential component of a sequential immunization regimen to induce V2-apex bnAbs. : Design of immunogens and strategies that can induce protective broadly neutralizing antibodies (bnAbs) is a priority for HIV vaccine development. Andrabi et al. design a chimpanzee simian immunodeficiency virus (SIV) envelope trimer immunogen that binds specifically to HIV V2-apex bnAbs and their unmutated versions. The SIV trimer immunogen induces HIV-specific neutralizing antibodies (nAbs) in a favorable animal model. Keywords: human immunodeficiency virus, simian immunodeficiency virus, broadly neutralizing antibodies, HIV envelope trimer, chimpanzee SIV envelope trimer, glycan shield, V2-apex bnAb site, immunization strategies, HIV vaccine
