A highly efficacious live attenuated mumps virus-based SARS-CoV-2 vaccine candidate expressing a six-proline stabilized prefusion spike

Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2201616119. doi: 10.1073/pnas.2201616119. Epub 2022 Jul 27.


With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)-based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P-M or F-SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P-M gene junction was more efficient than from the F-SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1-/- mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.

Keywords: SARS-CoV-2; mumps virus; vaccine.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • COVID-19 Vaccines* / genetics
  • COVID-19 Vaccines* / immunology
  • COVID-19* / prevention & control
  • Immunogenicity, Vaccine
  • Measles-Mumps-Rubella Vaccine* / genetics
  • Measles-Mumps-Rubella Vaccine* / immunology
  • Mesocricetus
  • Mice
  • Mumps virus / genetics
  • Mumps virus / immunology
  • Proline / genetics
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus* / genetics
  • Spike Glycoprotein, Coronavirus* / immunology
  • Vaccine Efficacy*
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Measles-Mumps-Rubella Vaccine
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Attenuated
  • spike protein, SARS-CoV-2
  • Proline

Supplementary concepts

  • SARS-CoV-2 variants