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Published on: November 1, 2011
A protease activation mutant, MVCES1, as a safe and potent live vaccine derived from currently prevailing Sendai
Abstract:
Sendai virus fresh isolates were shown to be antigenically different from the prototype Fushimi strain that had long been passaged in embryonated chicken eggs. Phylogenetic analysis of the hemagglutinin-neuraminidase genes also revealed the difference between these two virus groups. Both trypsin-resistant and elastase-sensitive mutations were additionally introduced to an LLC-MK2-cell-adapted and attenuated mutant derived from one of the fresh isolates. This protease activation mutant (MVCES1) showed the same antigenicity as the fresh isolates, and as a result of a single cycle of growth in lungs, it could confer better protection on mice against challenge infection with the currently prevailing Sendai virus than TR-5, which is a trypsin-resistant mutant derived from the Fushimi strain. The eligibility of MVCES1 as an attenuated live vaccine of Sendai virus is discussed.
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.

