A protease activation mutant, MVCES1, as a safe and potent live vaccine derived from currently prevailing Sendai

X L Wang1, M Itoh, H Hotta

  • 1Department of Microbiology, Kobe University School of Medicine, Japan.

Insights

Fresh Sendai virus isolates differ antigenically from older strains. A novel mutant (MVCES1) offers improved protection in mice, suggesting its potential as an attenuated live vaccine.

Area of Science:

  • Virology
  • Immunology
  • Vaccinology

Background:

  • Sendai virus (SeV) strains exhibit antigenic variation, particularly between fresh isolates and laboratory-passaged prototypes like the Fushimi strain.
  • Phylogenetic analysis of hemagglutinin-neuraminidase (HN) genes confirms genetic divergence between fresh SeV isolates and the Fushimi strain.

Purpose of the Study:

  • To investigate the antigenic and genetic differences between fresh Sendai virus isolates and a long-passaged strain.
  • To develop and evaluate a novel attenuated Sendai virus mutant (MVCES1) for enhanced vaccine potential.

Main Methods:

  • Comparative antigenic analysis of fresh SeV isolates and the Fushimi strain.
  • Phylogenetic analysis of HN genes.
  • Introduction of trypsin-resistant and elastase-sensitive mutations into an attenuated SeV mutant (MVCES1).
  • Assessment of MVCES1's protective efficacy in a mouse model against challenge infection.

Main Results:

  • Fresh Sendai virus isolates demonstrated significant antigenic differences compared to the Fushimi strain.
  • Phylogenetic analysis confirmed genetic divergence in HN genes.
  • The engineered mutant MVCES1 retained the antigenicity of fresh isolates.
  • MVCES1 provided superior protection in mice against prevailing Sendai virus challenge compared to a control mutant (TR-5).

Conclusions:

  • The engineered mutant MVCES1 exhibits promising characteristics for an attenuated live Sendai virus vaccine.
  • MVCES1's improved protective efficacy highlights its potential for controlling current Sendai virus infections.

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