AAV11 Vector Capsid Optimization for Vaccine Potency
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Solution Overview
Problem
Current AAV-based vaccines require higher doses and have limited potency and adaptability to variants of concern, necessitating optimization for improved efficacy and reduced dosing.
Innovation Solution
Development of an AAV11 vector with modified capsid proteins and optimized promoter elements, such as the Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE) and synthetic polyadenylation sequences, to enhance immune response and adaptability, specifically targeting immunogenic polypeptides like coronavirus spike proteins for improved immunogenicity and reduced dosing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional AAV-based vaccines are used, then vaccine delivery is achieved, but higher doses are required and potency is limited
Solution Approach 1:
The patent modifies the AAV capsid protein sequence by introducing amino acid substitutions, deletions, and insertions to optimize viral entry efficiency and cellular uptake. These parameter changes in the capsid structure enable improved transduction at lower doses while maintaining or enhancing immunogenicity and protective efficacy
Solution Approach 2:
The vaccine construct combines multiple functional elements including the modified AAV11 capsid, WPRE posttranscriptional regulatory element, and synthetic polyadenylation sequences to create an optimized composite vector that enhances both delivery efficiency and immunogenic response at reduced dosing levels
2Duration of action of stationary object
If AAV-based vaccines are used, then durable immunity is achieved, but adaptability to variants of concern is limited
Solution Approach 1:
The patent employs a dynamic capsid design where the AAV11 capsid sequence can be systematically modified through amino acid substitutions, deletions, and insertions to adapt to different viral variants. This dynamic optimization of capsid structure maintains durable immunity while enabling rapid adaptation to emerging variants of concern
Solution Approach 2:
The optimized AAV11 vector platform serves multiple functions including delivering immunogenic polypeptides for current variants, adapting to future variants through sequence modification, and maintaining long-term immunogenicity. The universal platform can be applied across different coronavirus variants and potentially other pathogens
3Ease of manufacture
If standard AAV vectors are used, then vaccine production is achieved, but manufacturing efficiency and scalability need optimization
Solution Approach 1:
The patent optimizes manufacturing parameters by modifying the AAV11 capsid sequence to improve viral assembly efficiency, particle yield, and transduction effectiveness. These parameter changes enable more efficient production processes while maintaining the ability to scale manufacturing capacity to meet public health needs
Data Source
AI summary
The present application relates to compositions and methods for eliciting an immune response in a subject using an Adeno-Associated Virus (AAV) AAV11 vector comprising an AAV11 capsid protein and a nucleic acid encoding a transgene operably linked to a promoter, wherein the transgene encodes an immunogenic polypeptide. Further disclosed are immunogenic polypeptides that are used for the compositions and methods.