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Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates.
Francica, Joseph R; Flynn, Barbara J; Foulds, Kathryn E; Noe, Amy T; Werner, Anne P; Moore, Ian N; Gagne, Matthew; Johnston, Timothy S; Tucker, Courtney; Davis, Rachel L; Flach, Britta; O'Connell, Sarah; Andrew, Shayne F; Lamb, Evan; Flebbe, Dillon R; Nurmukhambetova, Saule T; Donaldson, Mitzi M; Todd, John-Paul M; Zhu, Alex Lee; Atyeo, Caroline; Fischinger, Stephanie; Gorman, Matthew J; Shin, Sally; Edara, Venkata Viswanadh; Floyd, Katharine; Lai, Lilin; Boyoglu-Barnum, Seyhan; Van De Wetering, Renee; Tylor, Alida; McCarthy, Elizabeth; Lecouturier, Valerie; Ruiz, Sophie; Berry, Catherine; Tibbitts, Timothy; Andersen, Hanne; Cook, Anthony; Dodson, Alan; Pessaint, Laurent; Van Ry, Alex; Koutsoukos, Marguerite; Gutzeit, Cindy; Teng, I-Ting; Zhou, Tongqing; Li, Dapeng; Haynes, Barton F; Kwong, Peter D; McDermott, Adrian; Lewis, Mark G; Fu, Tong Ming; Chicz, Roman.
  • Francica JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Flynn BJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Foulds KE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Noe AT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Werner AP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Moore IN; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Gagne M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Johnston TS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Tucker C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Davis RL; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Flach B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • O'Connell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Andrew SF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Lamb E; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Flebbe DR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Nurmukhambetova ST; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Donaldson MM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Todd JM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Zhu AL; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Atyeo C; Ph.D. program in Immunology and Virology, University of Duisburg-Essen, Essen, Germany.
  • Fischinger S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Gorman MJ; Ph.D. program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02138, USA.
  • Shin S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Edara VV; Ph.D. program in Immunology and Virology, University of Duisburg-Essen, Essen, Germany.
  • Floyd K; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Lai L; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
  • Boyoglu-Barnum S; Centers for Childhood Infections and Vaccines, Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.
  • Van De Wetering R; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.
  • Tylor A; Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
  • McCarthy E; Centers for Childhood Infections and Vaccines, Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.
  • Lecouturier V; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.
  • Ruiz S; Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
  • Berry C; Centers for Childhood Infections and Vaccines, Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.
  • Tibbitts T; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.
  • Andersen H; Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
  • Cook A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Dodson A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Pessaint L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Van Ry A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20814, USA.
  • Koutsoukos M; Sanofi Pasteur, Marcy l'Etoile, France.
  • Gutzeit C; Sanofi Pasteur, Marcy l'Etoile, France.
  • Teng IT; Sanofi Pasteur, Marcy l'Etoile, France.
  • Zhou T; Sanofi Pasteur, 38 Sidney Street, Cambridge, MA 02139, USA.
  • Li D; Bioqual Inc., Rockville, MD 20850, USA.
  • Haynes BF; Bioqual Inc., Rockville, MD 20850, USA.
  • Kwong PD; Bioqual Inc., Rockville, MD 20850, USA.
  • McDermott A; Bioqual Inc., Rockville, MD 20850, USA.
  • Lewis MG; Bioqual Inc., Rockville, MD 20850, USA.
  • Fu TM; GSK, Wavre, Belgium.
  • Chicz R; GSK, Rixensart, Belgium.
Sci Transl Med ; 13(607)2021 08 18.
Article in English | MEDLINE | ID: covidwho-1329034
ABSTRACT
Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike protein trimers (preS dTM) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHPs). Binding and functional neutralization assays and systems serology revealed that the vaccinated NHP developed AS03-dependent multifunctional humoral responses that targeted distinct domains of the spike protein and bound to a variety of Fc receptors mediating immune cell effector functions in vitro. The neutralizing 50% inhibitory concentration titers for pseudovirus and live SARS-CoV-2 were higher than titers for a panel of human convalescent serum samples. NHPs were challenged intranasally and intratracheally with a high dose (3 × 106 plaque forming units) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days after challenge, vaccinated NHPs showed rapid control of viral replication in both the upper and lower airways. Vaccinated NHPs also had increased spike protein-specific immunoglobulin G (IgG) antibody responses in the lung as early as 2 days after challenge. Moreover, passive transfer of vaccine-induced IgG to hamsters mediated protection from subsequent SARS-CoV-2 challenge. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine were sufficient to mediate protection against SARS-CoV-2 in NHPs and that rapid anamnestic antibody responses in the lung may be a key mechanism for protection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Topics: Vaccines Limits: Animals Language: English Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Scitranslmed.abi4547

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / COVID-19 Topics: Vaccines Limits: Animals Language: English Journal subject: Science / Medicine Year: 2021 Document Type: Article Affiliation country: Scitranslmed.abi4547