Designed Coronavirus Spike Protein Sequences for Variant Coverage
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current vaccines against coronaviruses, particularly RNA viruses, face challenges such as limited breadth of protection due to viral strain variation, empirical immunogen selection, and time-consuming development, leading to issues like antibody-dependent enhancement and immune evasion by emerging variants.
Innovation Solution
Development of novel coronavirus spike protein sequences, including full-length, truncated, and receptor binding domain (RBD) polypeptides with specific amino acid modifications to elicit a broadly neutralizing immune response, reducing the risk of antibody-dependent enhancement and immune evasion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If wild-type field isolate glycoproteins are used as vaccine antigens, then vaccine development is simplified, but breadth of protection is limited due to viral variation
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the spike protein vaccine antigen. Specifically, it introduces non-conservative amino acid substitutions at positions 484 (K→E), 496 (K→E), and 501 (Y→C) in the receptor binding domain, creating a chimeric spike protein that combines characteristics of different coronavirus strains to achieve broad protection across multiple lineages
2Adaptability or versatility
If empirical immunogen selection is used, then vaccine development is more flexible, but the process becomes slow and time-consuming
Solution Approach 1:
The patent applies preliminary action by pre-designing and pre-optimizing the spike protein sequence based on computational algorithms and structural biology principles before vaccine formulation. The chimeric spike protein was designed in advance with specific amino acid modifications to enhance immunogenicity and broad coverage, eliminating the need for trial-and-error selection during the vaccine development process
3Loss of time
If current vaccine candidates are used, then vaccine deployment is faster, but emerging variants can evade immune response
Solution Approach 1:
The patent applies universality by creating a chimeric spike protein that combines conserved regions from multiple coronavirus lineages (alpha, beta, gamma, and delta) into a single vaccine antigen. This universal design enables the vaccine to elicit neutralizing antibodies that recognize and neutralize variants from different lineages, including emerging variants like Delta and Omicron, thereby maintaining reliability across evolving viral strains
4Speed
If RNA virus vaccines are developed, then vaccine response is rapid, but antibody-dependent enhancement and immune evasion occur
Solution Approach 1:
The patent applies local quality by making targeted modifications specifically in the receptor binding domain (RBD) of the spike protein, where amino acid substitutions are introduced at critical positions (484, 496, 501) that are involved in host cell receptor interaction. These localized changes in the RBD region enhance the vaccine's ability to induce neutralizing antibodies without compromising the overall structural integrity or causing harmful effects like antibody-dependent enhancement
Data Source
AI summary
Designed coronavirus polypeptide sequences are described, and their use as vaccines against viruses of the coronavirus family. The designed sequences include designed coronavirus spike (S) proteins and fragments thereof, including designed full-length S protein sequences SEQ ID NOs: 88, 87, and 53. Designed coronavirus envelope (E), membrane (M), and nucleocapsid (N) protein sequences are also described, and their use as vaccines. Nucleic acid molecules encoding the polypeptides, vectors, fusion proteins, pharmaceutical compositions, cells, and their use as vaccines against viruses of the coronavirus family are also described.