Rabies Virus Vector Prime Boost Regimen for Targeted Antigen Response
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Solution Overview
Problem
Recombinant viruses used in vaccinology often result in immune responses that dominate against the virus vector over the foreign antigen, and existing adjuvants used to enhance vaccine potency are associated with reactogenicity and toxicity, making it challenging to achieve a potent immune response without adverse reactions.
Innovation Solution
A prime/boost immunization regimen using attenuated recombinant rabies virus expressing foreign protein antigens, where the virus is attenuated through mutations in the glycoprotein gene, and a booster composition without adjuvants is administered to enhance the immune response specifically to the foreign antigen.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recombinant viruses are used to express foreign antigens, then immune response to foreign antigen is induced, but immune response against virus vector dominates over response to foreign antigen
Solution Approach 1:
The patent extracts the foreign antigen from the virus vector context and delivers it as a separate purified protein component in the booster composition. This separation allows the immune system to focus on the foreign antigen without being dominated by responses to viral vector components, thereby resolving the contradiction between inducing foreign antigen response and avoiding vector-dominated response.
Solution Approach 2:
The patent employs a two-stage immunization strategy where the virus vector is used first for prime immunization to establish initial immune recognition, followed by a booster with purified foreign antigen. This preliminary action with the vector prepares the immune system, and the subsequent booster reinforces specificity to the foreign antigen, preventing vector response dominance.
2Reliability
If adjuvants are used to enhance vaccine potency, then immune response is enhanced, but reactogenicity and toxicity occur
Solution Approach 1:
The patent replaces traditional adjuvants with a simplified booster composition containing only the purified foreign antigen in a safe carrier. This disposable, simple formulation achieves enhanced immune response through the prime-boost strategy without introducing adjuvant-related reactogenicity or toxicity, effectively resolving the contradiction between potency enhancement and safety.
3Productivity
If traditional adjuvants are used in booster composition, then immune response is enhanced, but adverse inflammatory mechanisms are induced
Solution Approach 1:
The patent extracts and removes adjuvants from the booster composition, using only the purified foreign antigen delivered in a safe carrier solution. This extraction eliminates the source of adverse inflammatory mechanisms while maintaining immune response enhancement through the optimized prime-boost immunization regimen with the virus vector followed by purified antigen booster.
Data Source
AI summary
An immune response in a subject is elicited by a regiment comprising immunization with an attenuated recombinant rabies virus encoding at least one foreign protein antigen, and booster immunization with the at least one foreign protein antigen in a vehicle that does not contain adjuvant. The foreign protein antigen may comprise a prion protein antigen, a cancer-associated antigens, a viral antigen, a bacterial antigens, or a protozoal antigen. The prime/boost regimen produces predominantly IgG 2A/C and IgG 2B antibodies against the foreign protein antigen, indicating a TH1 response. Rabies virus attenuation may be provided, for example, by one or more mutations in the rabies glycoprotein gene which confers attenuation of pathogenicity.