CMV Surface Protein Complex for Subunit Vaccine Design
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Solution Overview
Problem
Current methods lack effective vaccines and treatments for cytomegalovirus (CMV) infections, particularly in immunocompromised individuals and pregnant women, and there is a need for screening assays to identify molecules that inhibit CMV infectivity.
Innovation Solution
Development of immunogenic compositions and vaccines featuring a complex of CMV proteins including pUL128, pUL131, and optionally other virion constituents like gH or gB, which induce an immune response and can be used to create subunit vaccines or nucleic acid vaccines to combat CMV infections.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current vaccine and treatment methods are used, then CMV infections can be managed in some cases, but there is no effective preventive vaccine or cure for CMV infection, particularly in immunocompromised individuals and pregnant women
Solution Approach 1:
The patent segments the CMV virion complex into specific protein components (pUL128, pUL130, pUL131, gH, gL, gB) to create subunit vaccines. This segmentation allows for targeted immunogenic compositions that focus on critical surface proteins involved in cell entry and infectivity, rather than using whole virus approaches
Solution Approach 2:
The patent changes the parameter of vaccine composition by defining specific stoichiometric ratios and combinations of CMV proteins (pUL128:pUL130:pUL131:gH:gL:gB) to optimize immune response. This parameter optimization addresses the lack of effective vaccines by creating precisely formulated immunogenic compositions
2Ease of manufacture
If laboratory strains with restricted tropism are used, then vaccine production is simplified, but the strains have lost the ability to infect epithelial and endothelial cells, which are critical targets for CMV pathogenesis
Solution Approach 1:
The patent extracts the critical surface protein complex (pUL128, pUL130, pUL131, gH, gL, gB) from the whole virus particle to create subunit vaccines. This extraction allows the vaccine to retain immunogenicity for critical cell types while avoiding the tropism restriction problem of laboratory strains
Solution Approach 2:
The patent uses the pUL128-pUL130-pUL131-gH-gL-gB protein complex as an intermediary that mediates the immune response against CMV-infected epithelial and endothelial cells. This intermediary approach allows vaccination without using live virus that could replicate in restricted cell types
3Adaptability or versatility
If screening assays are developed to identify molecules that inhibit CMV infectivity, then new therapeutic targets can be found, but there is currently no established screening system for identifying such molecules
Solution Approach 1:
The patent creates a self-service screening assay where the CMV surface protein complex itself serves as the target for identifying inhibitory molecules. The assay system uses the defined protein complex to screen for compounds that block CMV infectivity, allowing the system to identify new therapeutic agents without requiring complex external validation systems
Data Source
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AI summary
Immunogenic compositions and prophylactic or therapeutic vaccines for use in protecting and treating against human cytomegalovirus (CMV) are disclosed. Subunit vaccines comprising a human CMV protein complex comprising pUL128 or pUL130, and nucleic acid vaccines comprising at least one nucleic acid encoding a CMV protein complex comprising pUL128 or pUL130 are described. Also disclosed are therapeutic antibodies reactive against a CMV protein complex comprising pUL128 or pUL130, as well as methods for screening compounds that inhibit CMV infection of epithelial and endothelial cells, methods for immunizing a subject against CMV infection, methods for determining the capability of neutralizing antibodies to inhibit human CMV infection of cell types other than fibroblasts, and methods of diminishing an CMV infection.