Chimeric Coronavirus Spike Protein Stabilization
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Solution Overview
Problem
Current vaccines for SARS-CoV-2 and other coronaviruses face challenges in effectively preventing transmission and inducing sterile immunity, particularly in animals like cats and ferrets, where the virus can shed and potentially infect humans, and there is a need for improved immunogenicity and stability of the spike protein to counter the spread of COVID-19.
Innovation Solution
Development of recombinant vectors encoding chimeric coronavirus spike proteins with modified transmembrane and C-terminal domains from budding viruses, such as vesicular stomatitis virus, and stabilization through proline substitutions, which are used in immunogenic compositions and vaccines to enhance immunogenicity and prevent transmission.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current vaccines are used for SARS-CoV-2 and other coronaviruses, then some level of immunity is induced, but transmission prevention is ineffective and sterile immunity is not achieved, particularly in animals like cats and ferrets
Solution Approach 1:
The patent modifies the spike protein by changing parameters such as adding proline substitutions (e.g., at positions 986-987) and altering the transmembrane and C-terminal domains. These parameter changes in the protein sequence stabilize the spike protein in a prefusion state and enhance immunogenicity, leading to effective transmission prevention and sterile immunity in animal models
Solution Approach 2:
The patent creates chimeric spike proteins that combine elements from different coronavirus species (e.g., SARS-CoV-2 spike protein fused with IBV spike protein domains). This composite approach produces vaccines that induce broad immunity across multiple coronavirus types, achieving both transmission prevention and sterile immunity in various animal models including cats, ferrets, and poultry
2Reliability
If the spike protein is used in vaccines, then immunogenicity is achieved, but the spike protein lacks stability and proper conformational stability
Solution Approach 1:
The patent introduces proline substitutions at specific positions in the spike protein sequence (e.g., positions 986-987 in SARS-CoV-2 spike protein). These parameter changes stabilize the protein's three-dimensional structure in a prefusion conformation, preventing premature degradation and ensuring proper presentation to the immune system, thereby maintaining both immunogenicity and structural stability
Solution Approach 2:
The patent makes local modifications to specific domains of the spike protein, particularly in the transmembrane and C-terminal regions. By altering these local areas while preserving the receptor-binding domain, the patent maintains immunogenicity through the RBD while improving overall protein stability and conformational integrity through the modified regions
3Object-generated harmful factors
If the virus sheds in animals, then transmission occurs, but effective protection against infection and transmission is not achieved
Solution Approach 1:
The patent modifies vaccine parameters by using stabilized prefusion spike proteins with proline substitutions and altered membrane domains. These changes enhance the vaccine's ability to induce neutralizing antibodies that block viral shedding, achieving effective protection against transmission in animal models including cats, ferrets, and poultry
Solution Approach 2:
The patent develops chimeric spike proteins that combine conserved regions from multiple coronavirus species. This composite approach induces broad-spectrum immunity that effectively blocks shedding and transmission across different coronavirus types, achieving reliable protection against both infection and transmission in various animal models
Data Source
AI summary
The present invention provides recombinant vectors encoding a chimeric coronavirus spike protein. The present invention further provides new immunogenic compositions and vaccines comprising these recombinant vectors. Methods of administering these immunogenic compositions and vaccines to animal subjects, including humans, felines, and avians, to protect them against coronaviruses also are included. Methods of making the immunogenic compositions and vaccines alone or in combinations with other protective agents are provided too.