Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates.

Autor: Francica JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Flynn BJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Foulds KE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Noe AT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Werner AP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Moore IN; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Gagne M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Johnston TS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Tucker C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Davis RL; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Flach B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., O'Connell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Andrew SF; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Lamb E; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Flebbe DR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Nurmukhambetova ST; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Donaldson MM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Todd JM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Zhu AL; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.; PhD program in Immunology and Virology, University of Duisburg-Essen, Essen, Germany., Atyeo C; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.; PhD program in Virology, Division of Medical Sciences, Harvard University, Boston, MA, USA., Fischinger S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.; PhD program in Immunology and Virology, University of Duisburg-Essen, Essen, Germany., Gorman MJ; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Shin S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Edara VV; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.; Yerkes National Primate Research Center, Atlanta, GA 30329, USA., Floyd K; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.; Yerkes National Primate Research Center, Atlanta, GA 30329, USA., Lai L; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.; Yerkes National Primate Research Center, Atlanta, GA 30329, USA., Tylor A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., McCarthy E; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Lecouturier V; Sanofi Pasteur, Marcy l'Etoile, France., Ruiz S; Sanofi Pasteur, Marcy l'Etoile, France., Berry C; Sanofi Pasteur, Marcy l'Etoile, France., Tibbitts T; Sanofi Pasteur, 38 Sidney Street, Cambridge, MA 02139, USA., Andersen H; Bioqual, Inc., Rockville, MD, USA., Cook A; Bioqual, Inc., Rockville, MD, USA., Dodson A; Bioqual, Inc., Rockville, MD, USA., Pessaint L; Bioqual, Inc., Rockville, MD, USA., Ry AV; Bioqual, Inc., Rockville, MD, USA., Koutsoukos M; GSK, Wavre, Belgium., Gutzeit C; GSK, Rixensart, Belgium., Teng IT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Li D; Duke Human Vaccine Institute, Duke University, Durham, NC 27708, USA., Haynes BF; Duke Human Vaccine Institute, Duke University, Durham, NC 27708, USA., Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., McDermott A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Lewis MG; Bioqual, Inc., Rockville, MD, USA., Fu TM; Sanofi Pasteur, 38 Sidney Street, Cambridge, MA 02139, USA., Chicz R; Sanofi Pasteur, 38 Sidney Street, Cambridge, MA 02139, USA., van der Most R; GSK, Rixensart, Belgium., Corbett KS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Suthar MS; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.; Yerkes National Primate Research Center, Atlanta, GA 30329, USA., Alter G; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA., Roederer M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Sullivan NJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Douek DC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Casimiro D; Sanofi Pasteur, 38 Sidney Street, Cambridge, MA 02139, USA., Seder RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2021 Mar 02. Date of Electronic Publication: 2021 Mar 02.
DOI: 10.1101/2021.03.02.433390
Abstrakt: 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 trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody F C receptors mediating effector functions in vitro . Pseudovirus and live virus neutralizing IC 50 titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3×10 6 PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials.
Competing Interests: Declaration of interests All authors have declared the following interests: VL, TB, CB, SR, TMF, DC, RC are Sanofi Pasteur employees and may hold stock. MK, RvdM, and CG are employees of the GSK group of companies and report ownership of GSK shares.
Databáze: MEDLINE
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