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Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance.
Cirelli, Kimberly M; Carnathan, Diane G; Nogal, Bartek; Martin, Jacob T; Rodriguez, Oscar L; Upadhyay, Amit A; Enemuo, Chiamaka A; Gebru, Etse H; Choe, Yury; Viviano, Federico; Nakao, Catherine; Pauthner, Matthias G; Reiss, Samantha; Cottrell, Christopher A; Smith, Melissa L; Bastidas, Raiza; Gibson, William; Wolabaugh, Amber N; Melo, Mariane B; Cossette, Benjamin; Kumar, Venkatesh; Patel, Nirav B; Tokatlian, Talar; Menis, Sergey; Kulp, Daniel W; Burton, Dennis R; Murrell, Ben; Schief, William R; Bosinger, Steven E; Ward, Andrew B; Watson, Corey T; Silvestri, Guido; Irvine, Darrell J; Crotty, Shane.
Afiliación
  • Cirelli KM; Division of Vaccine Discovery, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Carnathan DG; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322,
  • Nogal B; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), 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.
  • Martin JT; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Rodriguez OL; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Upadhyay AA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
  • Enemuo CA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Gebru EH; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Choe Y; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Viviano F; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • Nakao C; Division of Vaccine Discovery, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA.
  • Pauthner MG; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Reiss S; Division of Vaccine Discovery, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Cottrell CA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), 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.
  • Smith ML; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  • Bastidas R; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Gibson W; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40202, USA.
  • Wolabaugh AN; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
  • Melo MB; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Cossette B; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Kumar V; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA.
  • Patel NB; Yerkes NHP Genomics Core Laboratory, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
  • Tokatlian T; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Menis S; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
  • Kulp DW; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Vaccine and Immunotherapy Center, Wistar Institute, Philadel
  • Burton DR; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachus
  • Murrell B; Department of Medicine, University of California, San Diego, La Jolla, CA 92037, USA; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
  • Schief WR; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachus
  • Bosinger SE; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Yerkes NHP Genomics Core Laboratory, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
  • Ward AB; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), 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.
  • Watson CT; Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY 40202, USA.
  • Silvestri G; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322,
  • Irvine DJ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospit
  • Crotty S; Division of Vaccine Discovery, La Jolla Institute for Immunology (LJI), La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Scripps CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Medicine, University of California, San Diego, La
Cell ; 177(5): 1153-1171.e28, 2019 05 16.
Article en En | MEDLINE | ID: mdl-31080066
Conventional immunization strategies will likely be insufficient for the development of a broadly neutralizing antibody (bnAb) vaccine for HIV or other difficult pathogens because of the immunological hurdles posed, including B cell immunodominance and germinal center (GC) quantity and quality. We found that two independent methods of slow delivery immunization of rhesus monkeys (RMs) resulted in more robust T follicular helper (TFH) cell responses and GC B cells with improved Env-binding, tracked by longitudinal fine needle aspirates. Improved GCs correlated with the development of >20-fold higher titers of autologous nAbs. Using a new RM genomic immunoglobulin locus reference, we identified differential IgV gene use between immunization modalities. Ab mapping demonstrated targeting of immunodominant non-neutralizing epitopes by conventional bolus-immunized animals, whereas slow delivery-immunized animals targeted a more diverse set of epitopes. Thus, alternative immunization strategies can enhance nAb development by altering GCs and modulating the immunodominance of non-neutralizing epitopes.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos B / Anticuerpos Anti-VIH / VIH-1 / Inmunización Pasiva / Linfocitos T Colaboradores-Inductores / Centro Germinal / Anticuerpos Neutralizantes Límite: Animals Idioma: En Revista: Cell Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Linfocitos B / Anticuerpos Anti-VIH / VIH-1 / Inmunización Pasiva / Linfocitos T Colaboradores-Inductores / Centro Germinal / Anticuerpos Neutralizantes Límite: Animals Idioma: En Revista: Cell Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos