Chimeric SpiN Protein Vaccine for Variant Resistance
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Solution Overview
Problem
Current COVID-19 vaccines face challenges due to low antibody levels after the first dose, particularly in Brazil, and are vulnerable to SARS-CoV-2 variants with mutations in the Spike protein, which is the target antigen for neutralizing antibodies.
Innovation Solution
A chimeric protein called SpiN, composed of the nucleocapsid (N) protein linked to the Receptor Binding Domain (RBD) of the Spike protein, is developed to induce high levels of antibodies and stimulate T lymphocytes, providing broader immune response coverage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If vaccines use only the Spike protein or mRNA encoding Spike protein to induce neutralizing antibodies, then the vaccine mechanism is simple and targeted, but the antibody levels after first dose are low and the vaccine is vulnerable to variants with Spike protein mutations
Solution Approach 1:
The patent combines two different viral antigens (Spike protein RBD domain and Nucleocapsid protein) into a single chimeric protein vaccine formulation. This merging approach allows the vaccine to target multiple viral components simultaneously, generating both anti-Spike and anti-Nucleocapsid antibodies, thereby improving reliability against variants while managing complexity through a unified protein structure
Solution Approach 2:
The chimeric protein vaccine represents a composite antigen structure that integrates functional domains from different viral proteins. The Spike-RBD-Nucleocapsid chimera creates a composite material at the molecular level, combining the immunogenic properties of both parent proteins to achieve broader and more durable immune protection
2Reliability
If vaccines rely solely on inducing neutralizing antibodies against Spike protein, then the vaccine design is straightforward, but protection against high viral loads and severe disease forms is insufficient
Solution Approach 1:
The chimeric protein vaccine performs multiple immune functions simultaneously: it induces neutralizing antibodies against Spike protein for viral entry blocking, generates antibodies against Nucleocapsid for intracellular virus targeting, and stimulates T-cell responses for cellular immunity. This multi-functionality enhances protection against severe disease while managing the complexity of immune mechanisms through a single vaccine antigen
3Productivity
If the vaccine uses only the most abundant and immunogenic N protein, then the production is simplified and immunogenicity is high, but the coverage against viral variants with Spike mutations is reduced
Solution Approach 1:
The patent merges the highly immunogenic Nucleocapsid protein with the variant-targeting Spike-RBD domain in a chimeric structure. This combination maintains the production efficiency benefit of using the abundant N protein while adding variant adaptability through the Spike component, allowing the vaccine to respond to both current and emerging variants
Data Source
AI summary
The production process for a chimeric protein with SEQ ID No. 1, using the nucleotide sequence with SEQ ID No. 2; the chimeric protein defined by SEQ ID No. 1, the gene in SEQ ID No. 2 used for its production, immunogenic compositions containing the protein, and the use thereof to prepare vaccines for prophylaxis and prevention of infection and moderate and severe forms of COVID-19. The present technology falls within the field of human health, specifically in the field of preventive measures against infection with SARS-CoV2. It involves the production of a vaccine composition comprising a chimeric protein that prevents high viral loads and moderate and severe clinical forms of the disease by stimulating the immune system.