Multimeric SARS-CoV-2 RBD Polypeptides for Enhanced Immune Response
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Solution Overview
Problem
Current treatments and vaccines for SARS-CoV-2 infections face challenges in effectively addressing the rapid transmission and mutation of the virus, particularly in generating a robust immune response against various variants.
Innovation Solution
Development of isolated polypeptides comprising a receptor binding domain (RBD) with high identity to the SARS-CoV-2 RBD sequence, combined with a multimerization domain to create multimers, and administered via mRNA-based compositions to induce a strong immune response, including the use of pharmaceutical compositions with pharmaceutically acceptable carriers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments and vaccines are used, then some immune response is generated, but the response is insufficient against rapid transmission and mutation of the virus
Solution Approach 1:
The patent combines multiple RBD copies (60 or more) into a single multimeric structure, merging identical antigenic units to create a high-valency display that dramatically enhances immune recognition and neutralizing antibody generation against SARS-CoV-2 and its variants
Solution Approach 2:
The invention transitions from monomeric or low-valency RBD presentations to high-order multimers (60+ copies), effectively increasing the dimensionality of antigen display and creating a densely packed array that maximizes immune system engagement
2Reliability
If monomeric RBD is used, then the structure is simple, but the immune response is weak
Solution Approach 1:
Multiple RBD units are merged into a single multimeric polypeptide construct containing 60 or more RBD copies, where each RBD is separated by linkers, creating a unified structure that displays numerous identical antigens for enhanced immune recognition
Solution Approach 2:
Linker sequences serve as intermediaries between individual RBD units, allowing proper spacing and orientation while maintaining structural integrity of the multimeric construct, enabling each RBD to be independently accessible to antibodies
3Reliability
If low valency RBD presentation is used, then the polypeptide is easier to manufacture, but neutralizing antibody generation is insufficient
Solution Approach 1:
The patent merges 60 or more RBD copies into a single polypeptide chain with standardized linker sequences, creating a uniform high-valency construct that can be produced through recombinant expression systems, balancing manufacturing feasibility with enhanced immunogenicity
Solution Approach 2:
The invention changes the valency parameter from low (monomeric or dimeric) to high (60 or more copies), fundamentally altering the antigen presentation capacity while maintaining production through established molecular biology techniques for recombinant protein expression
Data Source
AI summary
The present disclosure provides polypeptides, and nucleic acids encoding the polypeptides, that include severe acute respiratory syndrome Co-V-2 (SARS-CoV-2) spike polypeptide receptor-binding domain (RBD) polypeptides or variants thereof, which are capable of multimerization and thus presenting multiple copies of the RBD to enhance the immune response generated when the polypeptide is administered to a subject. The disclosure also provides multimers, scaffolds, compositions, pharmaceutical compositions, and vaccines that include the polypeptides and/or nucleic acids that encode such polypeptides.