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Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates
Kizzmekia S. Corbett; Martha C. Nason; Britta Flach; Matthew Gagne; Timothy S. Johnston; Shruti N. Shah; Venkata Vishwanadh Edara; Katharine Floyd; Lilin Lai; Charlene McDanal; Joseph R. Francica; Barbara Flynn; Kai Wu; Angela Choi; Matthew Koch; Olubukola M. Abiona; Anne P. Werner; Gabriela S. Alvarado; Shayne F. Andrew; Mitzi M. Donaldson; Jonathan Fintzi; Dillon R. Flebbe; Evan Lamb; Amy T. Noe; Saule T. Nurmukhambetova; Samantha J. Provost; Anthony Cook; Alan Dodson; Andrew Faudree; Jack Greenhouse; Swagata Kar; Laurent Pessaint; Maciel Porto; Katelyn Steingrebe; Daniel Valentin; Serge Zouantcha; Kevin W. Bock; Mahnaz Minai; Bianca M. Nagata; Juan I. Moliva; Renee van de Wetering; Seyhan Boyoglu-Barnum; Kwanyee Leung; Wei Shi; Eun Sung Yang; Yi Zhang; John-Paul Todd; Lingshu Wang; Hanne Andersen; Kathryn E. Foulds; Darin K. Edwards; John R. K Mascola; Ian N. Moore; Mark G. Lewis; Andrea Carfi; David Montefiori; Mehul S. Suthar; Adrian McDermott; Nancy J. Sullivan; Mario Roederer; Daniel C. Douek; Barney S. Graham; Robert A. Seder.
Affiliation
  • Kizzmekia S. Corbett; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Martha C. Nason; Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Ma
  • Britta Flach; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Matthew Gagne; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Timothy S. Johnston; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Shruti N. Shah; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Venkata Vishwanadh Edara; Emory University
  • Katharine Floyd; Emory University
  • Lilin Lai; Emory University
  • Charlene McDanal; Department of Surgery, Duke University Medical Center, Durham, North Carolina, 27708; United States of America.
  • Joseph R. Francica; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Barbara Flynn; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Kai Wu; Moderna Inc., Cambridge, MA, 02139; United States of America
  • Angela Choi; Moderna Inc., Cambridge, MA, 02139; United States of America
  • Matthew Koch; Moderna Inc., Cambridge, MA, 02139; United States of America
  • Olubukola M. Abiona; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Anne P. Werner; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Gabriela S. Alvarado; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Shayne F. Andrew; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Mitzi M. Donaldson; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Jonathan Fintzi; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Dillon R. Flebbe; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Evan Lamb; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Amy T. Noe; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Saule T. Nurmukhambetova; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Samantha J. Provost; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Anthony Cook; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Alan Dodson; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Andrew Faudree; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Jack Greenhouse; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Swagata Kar; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Laurent Pessaint; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Maciel Porto; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Katelyn Steingrebe; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Daniel Valentin; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Serge Zouantcha; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Kevin W. Bock; Infectious Disease Pathogenesis Section; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United
  • Mahnaz Minai; National Institutes of Health
  • Bianca M. Nagata; Infectious Disease Pathogenesis Section; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United
  • Juan I. Moliva; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Renee van de Wetering; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Seyhan Boyoglu-Barnum; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Kwanyee Leung; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Wei Shi; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Eun Sung Yang; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Yi Zhang; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • John-Paul Todd; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Lingshu Wang; VRC/NIAID/NIH
  • Hanne Andersen; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Kathryn E. Foulds; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Darin K. Edwards; Moderna Inc
  • John R. K Mascola; Vaccine Research Center, NIAID, NIH
  • Ian N. Moore; Infectious Disease Pathogenesis Section; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United
  • Mark G. Lewis; Bioqual, Inc.; Rockville, Maryland, 20850; United States of America
  • Andrea Carfi; Moderna Inc., Cambridge, MA, 02139; United States of America
  • David Montefiori; Duke University
  • Mehul S. Suthar; Emory University
  • Adrian McDermott; Vaccine Research Center; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, Maryland, 20892; United States of Ameri
  • Nancy J. Sullivan; VRC, NIH
  • Mario Roederer; Vaccine Research Center
  • Daniel C. Douek; NIH Vaccine Research Center
  • Barney S. Graham; Vaccine Research Center, NIAID, NIH
  • Robert A. Seder; NIH
Preprint in En | PREPRINT-BIORXIV | ID: ppbiorxiv-440647
ABSTRACT
Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 g of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naive hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP. One-Sentence SummarymRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.
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Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Language: En Year: 2021 Document type: Preprint
Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Language: En Year: 2021 Document type: Preprint
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