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Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response
Nanda Kishore Routhu; Sailaja Gangadhara; Narayanaiah Cheedarla; Ayalnesh Shiferaw; Sheikh Abdul Rahman; Anusmita Sahoo; Pei-Yong Shi; Vineet D Menachery; Katharine Floyd; Stephanie Fischinger; Caroline Atyeo; Galit Alter; Mehul S Suthar; Rama Rao Amara.
Affiliation
  • Nanda Kishore Routhu; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
  • Sailaja Gangadhara; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
  • Narayanaiah Cheedarla; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
  • Ayalnesh Shiferaw; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
  • Sheikh Abdul Rahman; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
  • Anusmita Sahoo; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
  • Pei-Yong Shi; Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX, USA
  • Vineet D Menachery; University of Texas Medical Branch
  • Katharine Floyd; Department of Pediatrics, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA
  • Stephanie Fischinger; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA
  • Caroline Atyeo; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA
  • Galit Alter; Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA
  • Mehul S Suthar; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
  • Rama Rao Amara; Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
Preprint in En | PREPRINT-BIORXIV | ID: ppbiorxiv-175166
ABSTRACT
There is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.Competing Interest StatementThe authors have declared no competing interest.View Full Text
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Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Language: En Year: 2020 Type: Preprint
Fulltext
Print
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Full text: 1 Collection: 09-preprints Database: PREPRINT-BIORXIV Language: En Year: 2020 Type: Preprint