Chimeric Sindbis-WEEV Vaccine Attenuation
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Solution Overview
Problem
Current vaccines for Western equine encephalitis virus (WEEV) are inadequate for the general population, particularly ineffective in infants and pose risks due to the need for multiple doses and potential encephalitis from live virus presence, with challenges in producing and handling inactivated vaccines.
Innovation Solution
Development of a recombinant chimeric Sindbis-Western equine encephalitis virus using Sindbis virus cDNA fragments, Eastern equine encephalitis virus cDNA fragments, and Western equine encephalitis virus cDNA fragments to create attenuated and inactivated vaccines that elicit immune responses without causing disease, allowing for safer and more efficient production and use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If live Western equine encephalitis virus vaccine is used, then immunity is induced, but encephalitis risk and multiple doses are required
Solution Approach 1:
The patent uses a Sindbis virus backbone as an intermediary carrier that expresses Western equine encephalitis virus antigens. This chimeric virus serves as a mediator between the live virus vaccine approach and safety requirements, providing immunity induction while reducing encephalitis risk through the Sindbis virus framework that lacks neuroinvasive properties.
Solution Approach 2:
The patent modifies the viral genome by incorporating specific mutations in the Western equine encephalitis virus genes within the Sindbis backbone. These parameter changes (mutations) attenuate the virus to reduce encephalitis risk while maintaining antigenicity for immunity induction, allowing single-dose administration.
2Object-affected harmful factors
If inactivated Western equine encephalitis virus vaccine is used, then safety is improved, but production complexity and handling difficulties increase
Solution Approach 1:
The patent employs a live attenuated chimeric Sindbis-Western equine encephalitis virus that can be handled and administered without complex inactivation procedures. The virus maintains live virus characteristics for effective immunity induction but with attenuated properties that simplify production and handling compared to traditional inactivated vaccines requiring formalin or other inactivants.
3Reliability
If traditional Western equine encephalitis virus vaccine is used, then protection is provided, but multiple doses and long duration are required
Solution Approach 1:
The chimeric Sindbis-Western equine encephalitis virus vaccine provides continuous immune protection through a single dose. The virus replicates efficiently in the host, providing sustained antigen expression and immune stimulation that maintains protection over time, eliminating the need for multiple spaced doses required by traditional vaccines.
Data Source
AI summary
The present invention discloses a chimeric alphavirus comprising a Sindbis virus cDNA fragment, an Eastern equine encephalitis virus cDNA fragment, a Western equine encephalitis virus cDNA fragment or a combination thereof. The present also discloses the use of this chimeric alphavirus as vaccines and in serological and diagnostic assays.