Vaccination induces broadly neutralizing antibody precursors to HIV gp41.

Autor:	Schiffner T; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Institute for Drug Discovery, Leipzig University Medical Faculty, Leipzig, Germany., Phung I; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA., Ray R; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Irimia A; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Tian M; Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA., Swanson O; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Lee JH; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Lee CD; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Marina-Zárate E; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA., Cho SY; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Huang J; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Ozorowski G; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Skog PD; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Serra AM; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Rantalainen K; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Allen JD; School of Biological Sciences, University of Southampton, Southampton, UK., Baboo S; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA., Rodriguez OL; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA., Himansu S; Moderna, Inc., Cambridge, MA, USA., Zhou J; Department of Computer Science, Dartmouth College, Hanover, NH, USA., Hurtado J; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Flynn CT; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., McKenney K; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Havenar-Daughton C; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA., Saha S; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA., Shields K; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA., Schultze S; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA., Smith ML; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA., Liang CH; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Toy L; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA., Pecetta S; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Lin YC; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Willis JR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Sesterhenn F; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Kulp DW; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Hu X; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Cottrell CA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Zhou X; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Ruiz J; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Wang X; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Nair U; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Kirsch KH; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Cheng HL; Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA., Davis J; Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA., Kalyuzhniy O; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Liguori A; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Diedrich JK; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA., Ngo JT; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Lewis V; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Phelps N; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Tingle RD; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Spencer S; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Georgeson E; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Adachi Y; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Kubitz M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Eskandarzadeh S; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Elsliger MA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Amara RR; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.; Department of Microbiology and Immunology, Emory School of Medicine, Atlanta, GA, USA., Landais E; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Briney B; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Multi-omics Vaccine Evaluation Consortium, The Scripps Research Institute, La Jolla, CA, USA.; San Diego Center for AIDS Research, The Scripps Research Institute, La Jolla, CA, USA., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA., Carnathan DG; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA., Silvestri G; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA., Watson CT; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA., Yates JR 3rd; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA., Paulson JC; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA., Crispin M; School of Biological Sciences, University of Southampton, Southampton, UK., Grigoryan G; Department of Computer Science, Dartmouth College, Hanover, NH, USA.; Department of Biological Sciences, Dartmouth College, Hanover, NH, USA.; Generate Biomedicines, Inc., Somerville, MA, USA., Ward AB; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA., Sok D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA., Alt FW; Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA., Wilson IA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. wilson@scripps.edu.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. wilson@scripps.edu.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA. wilson@scripps.edu., Batista FD; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. fbatista1@mgh.harvard.edu.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. fbatista1@mgh.harvard.edu., Crotty S; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. shane@lji.org.; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA. shane@lji.org.; Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA, USA. shane@lji.org., Schief WR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. schief@scripps.edu.; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA. schief@scripps.edu.; Moderna, Inc., Cambridge, MA, USA. schief@scripps.edu.
Jazyk:	angličtina
Zdroj:	Nature immunology [Nat Immunol] 2024 Jun; Vol. 25 (6), pp. 1073-1082. Date of Electronic Publication: 2024 May 30.
DOI:	10.1038/s41590-024-01833-w
Abstrakt:	A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features. (© 2024. The Author(s).)
Databáze:	MEDLINE
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