SARS-CoV-2 Epitope-Based Polypeptide Vaccine Design
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Solution Overview
Problem
The rapid global spread and high mortality rate of SARS-CoV-2 pose significant public health and socio-economic challenges, with no available treatments or vaccines, necessitating the development of effective vaccine candidates to reduce morbidity and mortality.
Innovation Solution
Identification of specific epitopes for SARS-CoV-2 vaccines through in silico analysis of amino-acid sequences using software like NetMHC-4.0, NetMHCII-2.3, BepiPred-2.0, and Discotope, to create candidate vaccines that include predicted MHC-I and -II epitopes, B cell epitopes, and regions homologous between SARS-CoV-2 and SARS-CoV-1, adapted for use in ready-to-use vaccine platforms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional vaccine development methods are used, then comprehensive immune response can be achieved, but development time is excessive and cannot meet urgent pandemic needs
Solution Approach 1:
The vaccine candidate is segmented into multiple distinct epitope regions (S1, S2, N, M, E proteins) that can be independently identified and combined. This segmentation allows for targeted immunogenic regions to be selected and assembled in different configurations, enabling rapid development of multiple vaccine candidates simultaneously while ensuring comprehensive immune coverage through inclusion of multiple viral protein targets
Solution Approach 2:
In silico epitope prediction and selection is performed in advance before experimental validation and vaccine manufacturing. Computational tools are used to pre-identify promising epitopes from SARS-CoV-2 proteome, predict their immunogenicity and T-cell recognition potential, and select optimal combinations. This preliminary computational screening accelerates the development process by filtering out non-promising candidates before resource-intensive wet lab work begins
2Reliability
If multiple epitope types are included to enhance immune response, then vaccine effectiveness improves, but vaccine composition complexity increases
Solution Approach 1:
Multiple distinct epitope sequences from different SARS-CoV-2 proteins (S1, S2, N, M, E) are merged into single polypeptide constructs or combined in viral-like particle formulations. This merging creates multi-epitope vaccine candidates that can elicit broad immune responses against multiple viral antigens simultaneously, enhancing protective efficacy while consolidating multiple immune targets into unified vaccine compositions
Solution Approach 2:
The vaccine platform is designed with universal applicability across different SARS-CoV-2 variants and can be adapted to other coronaviruses. The selection of conserved epitopes from multiple viral proteins creates a multi-functional vaccine that targets various viral components, providing broad-spectrum protection while using a standardized delivery platform that can be rapidly reconfigured for different pathogens
Data Source
AI summary
The present disclosure provides polypeptides derived from SARS-CoV-2 which have therapeutic use. One such polypeptide is a polypeptide, referred to as “Npep2,” is derived from the SARS-CoV-2 protein N and has at least 50 consecutive amino acids of the amino acid sequence having at least 90% identity with the amino acid sequence that ranges from the residue at position 276 to the residue at position 411 of SEQ ID NO:2. Further described are conjugates wherein a heterologous polypeptide is conjugated or fused to Npep2. The present disclosure further provides vaccines employing the polypeptides, polynucleotides encoding the polypeptides, and methods of vaccinating subjects against SARS-CoV-2 by administering a therapeutically effective amount of one or more of the polypeptides.