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Vaccination induces broadly neutralizing antibody precursors to HIV gp41.
Schiffner, Torben; Phung, Ivy; Ray, Rashmi; Irimia, Adriana; Tian, Ming; Swanson, Olivia; Lee, Jeong Hyun; Lee, Chang-Chun D; Marina-Zárate, Ester; Cho, So Yeon; Huang, Jiachen; Ozorowski, Gabriel; Skog, Patrick D; Serra, Andreia M; Rantalainen, Kimmo; Allen, Joel D; Baboo, Sabyasachi; Rodriguez, Oscar L; Himansu, Sunny; Zhou, Jianfu; Hurtado, Jonathan; Flynn, Claudia T; McKenney, Katherine; Havenar-Daughton, Colin; Saha, Swati; Shields, Kaitlyn; Schultze, Steven; Smith, Melissa L; Liang, Chi-Hui; Toy, Laura; Pecetta, Simone; Lin, Ying-Cing; Willis, Jordan R; Sesterhenn, Fabian; Kulp, Daniel W; Hu, Xiaozhen; Cottrell, Christopher A; Zhou, Xiaoya; Ruiz, Jennifer; Wang, Xuesong; Nair, Usha; Kirsch, Kathrin H; Cheng, Hwei-Ling; Davis, Jillian; Kalyuzhniy, Oleksandr; Liguori, Alessia; Diedrich, Jolene K; Ngo, Julia T; Lewis, Vanessa; Phelps, Nicole.
Afiliación
  • Schiffner T; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Phung I; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Ray R; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Irimia A; Institute for Drug Discovery, Leipzig University Medical Faculty, Leipzig, Germany.
  • Tian M; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Swanson O; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
  • Lee JH; The Ragon Institute of Mass General, MIT and Harvard, Cambridge, MA, USA.
  • Lee CD; IAVI Neutralizing Antibody Center, 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.
  • Cho SY; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Huang J; Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.
  • Ozorowski G; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Skog PD; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Serra AM; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Rantalainen K; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Allen JD; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Baboo S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Rodriguez OL; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Himansu S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Zhou J; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Hurtado J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Flynn CT; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • McKenney K; Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
  • Havenar-Daughton C; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Saha S; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Shields K; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Schultze S; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Smith ML; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Liang CH; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Toy L; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Pecetta S; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Lin YC; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA.
  • Willis JR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Sesterhenn F; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Kulp DW; 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.
  • Cottrell CA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Zhou X; 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.
  • Wang X; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Nair U; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Kirsch KH; School of Biological Sciences, University of Southampton, Southampton, UK.
  • Cheng HL; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA.
  • Davis J; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.
  • Kalyuzhniy O; Moderna, Inc., Cambridge, MA, USA.
  • Liguori A; Department of Computer Science, Dartmouth College, Hanover, NH, USA.
  • Diedrich JK; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
  • Ngo JT; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
  • Lewis V; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
  • Phelps N; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
Nat Immunol ; 25(6): 1073-1082, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38816615
ABSTRACT
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / Proteína gp41 de Envoltorio del VIH / Infecciones por VIH / VIH-1 / Vacunas contra el SIDA / Anticuerpos Neutralizantes / Macaca mulatta Límite: Animals / Female / Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Anti-VIH / Proteína gp41 de Envoltorio del VIH / Infecciones por VIH / VIH-1 / Vacunas contra el SIDA / Anticuerpos Neutralizantes / Macaca mulatta Límite: Animals / Female / Humans Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos