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.

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; Tylor, Alida; McCarthy, Elizabeth; Lecouturier, Valerie; Ruiz, Sophie; Berry, Catherine; Tibbitts, Timothy; Andersen, Hanne; Cook, Anthony; Dodson, Alan; Pessaint, Laurent; Ry, Alex Van; 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; van der Most, Robbert; Corbett, Kizzmekia S

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; Tylor, Alida; McCarthy, Elizabeth; Lecouturier, Valerie; Ruiz, Sophie; Berry, Catherine; Tibbitts, Timothy; Andersen, Hanne; Cook, Anthony; Dodson, Alan; Pessaint, Laurent; Ry, Alex Van; 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; van der Most, Robbert; Corbett, Kizzmekia S.

Afiliação

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.
Atyeo C; PhD 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; PhD program in Virology, Division of Medical Sciences, Harvard University, Boston, MA, USA.
Shin S; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
Edara VV; PhD 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.
Tylor A; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.
McCarthy E; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.
Lecouturier V; Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Ruiz S; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.
Berry C; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.
Tibbitts T; Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Andersen H; Centers for Childhood Infections and Vaccines; Children's Healthcare of Atlanta and Emory University, Department of Pediatrics, Atlanta, GA, 30329, USA.
Cook A; Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA.
Dodson A; Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
Pessaint L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Ry AV; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 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, USA.
Haynes BF; Bioqual, Inc., Rockville, MD, USA.
Kwong PD; Bioqual, Inc., Rockville, MD, USA.
McDermott A; Bioqual, Inc., Rockville, MD, USA.
Lewis MG; Bioqual, Inc., Rockville, MD, USA.
Fu TM; GSK, Wavre, Belgium.
Chicz R; GSK, Rixensart, Belgium.
van der Most R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Corbett KS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

bioRxiv ; 2021 Mar 02.

Article em En | MEDLINE | ID: mdl-33688652

ABSTRACT

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 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 FC receptors mediating effector functions in vitro. Pseudovirus and live virus neutralizing IC50 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 (3×106 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.

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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos