Ferritin Nanoparticle Spike Protein Multimers for Broad Coronavirus Immunity
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Solution Overview
Problem
The ongoing global pandemic of SARS-CoV-2 coronavirus necessitates the development of effective preventative and treatment therapies, with existing vaccines and therapies struggling to provide broad immunity against various coronavirus strains due to conformational evasion and limited cross-reactivity among SARS and MERS antibodies.
Innovation Solution
Design and production of modified coronavirus spike proteins, specifically recombinant fusion proteins forming multimeric complexes with ferritin nanoparticles, which present multiple copies of spike protein domains like RBD, NTD, and FP to induce a robust immunogenic response, including use of modified mRNAs and vectors for stable expression and integration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing vaccines and therapies are used, then some level of immunity is provided, but broad immunity against various coronavirus strains is not achieved due to conformational evasion and limited cross-reactivity
Solution Approach 1:
The spike protein is divided into functional domains (RBD, NTD, FP, S2) that are independently expressed and then assembled into multimeric complexes. This segmentation allows each domain to be optimized for its specific function while maintaining the ability to elicit cross-reactive antibodies against multiple coronavirus strains.
Solution Approach 2:
The invention creates composite protein structures by fusing coronavirus spike protein domains with multimeric scaffold proteins (ferritin, encapsulin). This composite approach generates particles that display multiple copies of antigenic domains in a stable, immunogenic configuration, enhancing both breadth and strength of immune response.
2Reliability
If modified coronavirus spike proteins are designed to form multimeric complexes with ferritin nanoparticles, then robust immunogenic response is induced, but protein design and production complexity increases
Solution Approach 1:
Multimeric scaffold proteins (ferritin, encapsulin) serve as intermediaries that simplify the design process. These pre-formed, stable nanoscaffolds provide a ready-made multimeric structure to which spike protein domains can be attached, avoiding the need to design complex multimeric interactions from scratch while ensuring proper folding and stability.
Solution Approach 2:
The multimeric scaffolds serve multiple functions: they provide structural stability, enable multivalent antigen display, facilitate self-assembly, and can be produced in various host systems. This multi-functionality reduces overall system complexity by consolidating multiple requirements into a single platform.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The approach elicits high titers of neutralizing antibodies and broad immune responses, effectively protecting against SARS-CoV-2 and other coronavirus strains by enhancing B cell receptor interaction and antigen trafficking to immune sites, thereby preventing severe infections.
Implementation Method 1
a self-assembling protein, wherein the fusion protein is comprised in a multimeric protein complex
Data Source
AI summary
The invention is directed to coronavirus based immunogens, including immunogens comprising spike protein and or domains thereof, comprised in multimeric complexes. Provided are also methods of using these immunogens to induce immunogenic responses in a subject.