Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform

Nat Commun. 2020 Nov 30;11(1):6121. doi: 10.1038/s41467-020-19819-1.

Abstract

Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology
  • COVID-19 Vaccines / immunology*
  • Coronavirus Nucleocapsid Proteins / immunology*
  • Genetic Vectors / immunology
  • Humans
  • Immunity, Cellular
  • Mice
  • Phosphoproteins / immunology
  • SARS-CoV-2 / immunology
  • Spike Glycoprotein, Coronavirus / immunology*
  • Vaccines, Attenuated / immunology
  • Vaccines, Synthetic / immunology*
  • Vaccinia virus / immunology
  • Viral Vaccines / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • COVID-19 Vaccines
  • Coronavirus Nucleocapsid Proteins
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Attenuated
  • Vaccines, Synthetic
  • Viral Vaccines
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2