Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice

Viruses. 2020 Sep 5;12(9):987. doi: 10.3390/v12090987.

Abstract

An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.

Keywords: RBD; SARS-CoV-2; influenza; intranasal; live attenuated vaccine; spike.

Publication types

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

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines* / administration & dosage
  • COVID-19 Vaccines* / genetics
  • COVID-19* / prevention & control
  • Coronavirus Infections
  • Fertility
  • Influenza A virus / genetics
  • Mice
  • Pandemics*
  • SARS-CoV-2 / genetics
  • Spike Glycoprotein, Coronavirus / genetics
  • Virion

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Spike Glycoprotein, Coronavirus
  • COVID-19 Vaccines