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

Yuexiu Zhang1, Mijia Lu1, K C Mahesh2

  • 1Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210.

Proceedings of the National Academy of Sciences of the United States of America
|July 27, 2022
PubMed

Insights

A novel recombinant mumps virus vaccine candidate expressing SARS-CoV-2 spike protein demonstrated strong immunogenicity and complete protection against COVID-19 variants in animal models, suggesting potential for a combined MMR vaccine.

Area of Science:

  • Virology
  • Vaccinology
  • Immunology

Background:

  • The urgent need for a safe and effective SARS-CoV-2 (COVID-19) vaccine for children.
  • The established safety and efficacy of the measles/mumps/rubella (MMR) vaccine in pediatric populations.
  • Development of live attenuated recombinant vaccines offers a promising platform for novel disease prevention.

Purpose of the Study:

  • To develop and evaluate novel live attenuated recombinant mumps virus (rMuV)-based SARS-CoV-2 vaccine candidates.
  • To optimize the expression and immunogenicity of SARS-CoV-2 prefusion spike protein (preS) within the rMuV backbone.
  • To assess the protective efficacy of the most promising vaccine candidate against SARS-CoV-2 challenge in animal models.

Main Methods:

  • Construction of rMuV vectors encoding stabilized SARS-CoV-2 preS genes (preS-2P and preS-6P) at different genomic locations.
  • Evaluation of preS gene expression efficiency in the rMuV genome.
  • Assessment of immunogenicity, including neutralizing antibody and mucosal immune responses, in mice and hamsters.
  • Challenge studies in IFNAR1-/- mice and golden Syrian hamsters with SARS-CoV-2 USA-WA1/2020 and Delta variants.

Main Results:

  • The rMuV-preS-6P vaccine candidate showed superior expression and immunogenicity compared to rMuV-preS-2P.
  • PreS-6P expression was more efficient at the P-M gene junction than the F-SH junction.
  • The rMuV-preS-6P vaccine induced robust neutralizing antibodies, mucosal IgA, and T cell responses.
  • Vaccinated animals were completely protected from challenge with both wild-type and Delta SARS-CoV-2 variants.
  • Sera neutralized SARS-CoV-2 variants of concern, including the Delta variant.

Conclusions:

  • The rMuV-preS-6P vaccine is a highly promising candidate for COVID-19 prevention.
  • This platform demonstrates potential for development into a tetravalent MMR vaccine offering protection against SARS-CoV-2.
  • Further development is warranted to explore its potential in pediatric and adult populations.

Keywords:
SARS-CoV-2mumps virusvaccine

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