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A modified vaccinia Ankara vector-based vaccine protects macaques from SARS-CoV-2 infection, immune pathology, and dysfunction in the lungs.
Routhu, Nanda Kishore; Cheedarla, Narayanaiah; Gangadhara, Sailaja; Bollimpelli, Venkata Satish; Boddapati, Arun K; Shiferaw, Ayalnesh; Rahman, Sheikh Abdul; Sahoo, Anusmita; Edara, Venkata Viswanadh; Lai, Lilin; Floyd, Katharine; Wang, Shelly; Fischinger, Stephanie; Atyeo, Caroline; Shin, Sally A; Gumber, Sanjeev; Kirejczyk, Shannon; Cohen, Joyce; Jean, Sherrie M; Wood, Jennifer S; Connor-Stroud, Fawn; Stammen, Rachelle L; Upadhyay, Amit A; Pellegrini, Kathryn; Montefiori, David; Shi, Pei-Yong; Menachery, Vineet D; Alter, Galit; Vanderford, Thomas H; Bosinger, Steven E; Suthar, Mehul S; Amara, Rama Rao.
  • Routhu NK; 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.
  • Cheedarla N; 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.
  • Gangadhara S; 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.
  • Bollimpelli VS; 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.
  • Boddapati AK; 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.
  • Shiferaw A; 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.
  • Rahman SA; 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.
  • Sahoo A; 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.
  • Edara VV; 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.
  • Lai L; 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.
  • Floyd K; 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.
  • Wang S; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Fischinger S; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Atyeo C; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Shin SA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Gumber S; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Kirejczyk S; Division of Pathology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Cohen J; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Jean SM; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Wood JS; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Connor-Stroud F; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Stammen RL; Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Upadhyay AA; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Pellegrini K; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Montefiori D; Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
  • Shi PY; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA.
  • Menachery VD; Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, TX, USA.
  • Alter G; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Vanderford TH; Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
  • Bosinger SE; 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.
  • Suthar MS; 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.
  • Amara RR; 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.
Immunity ; 54(3): 542-556.e9, 2021 03 09.
Article in English | MEDLINE | ID: covidwho-1101300
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccinia virus / Vaccines, DNA / COVID-19 Vaccines / Genetic Vectors / SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Animals Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.02.001

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Vaccinia virus / Vaccines, DNA / COVID-19 Vaccines / Genetic Vectors / SARS-CoV-2 / COVID-19 Topics: Vaccines Limits: Animals Language: English Journal: Immunity Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: J.immuni.2021.02.001