Variant mRNA Vaccine Composition for SARS-CoV-2 Strain Coverage
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Solution Overview
Problem
Existing COVID-19 vaccines, such as mRNA-1273, face challenges in effectively neutralizing emerging SARS-CoV-2 variants with mutations in the spike protein, particularly the B.1.1.7 and B.1.351 variants, which reduce antibody efficacy and increase transmission and potential mortality.
Innovation Solution
Development of variant vaccines comprising nucleic acids encoding SARS-CoV-2 antigens with specific amino acid mutations, administered alone or in combination with other vaccines, to induce immune responses against multiple circulating variants.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing COVID-19 vaccines (e.g., mRNA-1273) are used, then initial immune protection is achieved, but effectiveness against emerging SARS-CoV-2 variants with spike protein mutations is reduced
Solution Approach 1:
The vaccine composition is designed to dynamically adapt to emerging variants through the inclusion of multiple antigen variants. The formulation can be updated by replacing or adding different spike protein variants (e.g., B.1.1.7, B.1.351, P.1, D614G) based on circulating strains, allowing the vaccine to evolve alongside the virus while maintaining protective efficacy
Solution Approach 2:
The vaccine employs a composite antigen structure containing multiple spike protein variants from different SARS-CoV-2 strains. This composite approach combines antigens from ancestral strains (D614G) with variant strains (B.1.1.7, B.1.351, P.1) to create a multi-component vaccine that elicits broad immune responses against diverse viral variants simultaneously
2Reliability
If vaccines target only the ancestral SARS-CoV-2 strain, then initial vaccination is effective, but protection against variants with amino acid substitutions in RBD and NTD is reduced
Solution Approach 1:
The vaccine achieves universal protection against multiple SARS-CoV-2 variants by incorporating spike protein antigens from diverse strains. The multi-variant formulation functions against both ancestral strains and emerging variants (including B.1.1.7, B.1.351, P.1, and D614G), providing broad-spectrum immunity that addresses the limitations of strain-specific vaccines
Solution Approach 2:
The vaccine utilizes parameter changes in the antigen composition by incorporating spike proteins with different amino acid sequences from various variants. This includes variants with specific mutations in the receptor binding domain (RBD) and N-terminal domain (NTD), such as N501Y in B.1.1.7 and E484K in B.1.351, thereby expanding the immune response to cover diverse viral configurations
3Ease of manufacture
If a single antigen variant is used in the vaccine, then manufacturing is simpler, but immune response breadth against multiple circulating variants is limited
Solution Approach 1:
The vaccine formulation is segmented into multiple discrete antigen components, each representing a different SARS-CoV-2 variant. This segmentation allows for modular manufacturing where individual variant antigens can be produced separately and then combined, facilitating both simplified production processes and the ability to update specific components as new variants emerge
Data Source
AI summary
The disclosure provides coronavirus mRNA vaccines, including vaccines directed against spike proteins of one or more variant strains of SARS-CoV-2, as well as methods of using the vaccines.