A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs.
Nanda Kishore Routhu, Narayanaiah Cheedarla, Sailaja Gangadhara, Venkata Satish Bollimpelli, Arun K Boddapati, Ayalnesh Shiferaw, Sheikh Abdul Rahman, Anusmita Sahoo, Venkata Viswanadh Edara, Lilin Lai, Katharine Floyd, Shelly Wang, Stephanie Fischinger, Caroline Atyeo, Sally A Shin, Sanjeev Gumber, Shannon Kirejczyk, Joyce Cohen, Sherrie M Jean, Jennifer S Wood, Fawn Connor-Stroud, Rachelle L Stammen, Amit A Upadhyay, Kathryn Pellegrini, David Montefiori, Pei-Yong Shi, Vineet D Menachery, Galit Alter, Thomas H Vanderford, Steven E Bosinger, Mehul S Suthar, Rama Rao Amara
Author Information
Nanda Kishore Routhu: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Narayanaiah Cheedarla: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Sailaja Gangadhara: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Venkata Satish Bollimpelli: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Arun K Boddapati: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Ayalnesh Shiferaw: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Sheikh Abdul Rahman: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Anusmita Sahoo: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Venkata Viswanadh Edara: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
Lilin Lai: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
Katharine Floyd: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
Shelly Wang: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Stephanie Fischinger: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Caroline Atyeo: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Sally A Shin: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Sanjeev Gumber: Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Shannon Kirejczyk: Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Joyce Cohen: Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Sherrie M Jean: Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Jennifer S Wood: Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Fawn Connor-Stroud: Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Rachelle L Stammen: Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Amit A Upadhyay: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Kathryn Pellegrini: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
David Montefiori: Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
Pei-Yong Shi: Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
Vineet D Menachery: Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX, USA.
Galit Alter: Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Thomas H Vanderford: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Steven E Bosinger: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA.
Mehul S Suthar: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA.
Rama Rao Amara: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: ramara@emory.edu.
A combination of vaccination approaches will likely be necessary to fully control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Here, we show that modified vaccinia Ankara (MVA) vectors expressing membrane-anchored pre-fusion stabilized spike (MVA/S) but not secreted S1 induced strong neutralizing antibody responses against SARS-CoV-2 in mice. In macaques, the MVA/S vaccination induced strong neutralizing antibodies and CD8 T cell responses, and conferred protection from SARS-CoV-2 infection and virus replication in the lungs as early as day 2 following intranasal and intratracheal challenge. Single-cell RNA sequencing analysis of lung cells on day 4 after infection revealed that MVA/S vaccination also protected macaques from infection-induced inflammation and B cell abnormalities and lowered induction of interferon-stimulated genes. These results demonstrate that MVA/S vaccination induces neutralizing antibodies and CD8 T cells in the blood and lungs and is a potential vaccine candidate for SARS-CoV-2.
