Virus-Like Vesicle Vaccines for Durable SARS-CoV-2 and HCC Immunity
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Solution Overview
Problem
There is a need for effective vaccines against SARS-CoV-2 to control the pandemic and treat hepatocellular carcinoma (HCC), as existing vaccines face challenges with viral mutation and fading immunity, and current HCC treatments have high relapse and recurrence rates.
Innovation Solution
Development of virus-like vesicle (VLV) producing vectors that express SARS-CoV-2 antigens or GPC3 proteins, inducing immune responses through high-titer VLVs, including mutations to enhance immunogenicity and stability, administered to elicit memory T and B cell responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mRNA and adenovirus based vaccines are used, then initial immunity is induced, but viral mutation and fading immunity occur
Solution Approach 1:
The patent changes the fundamental parameter of the vaccine platform from mRNA/adenovirus to virus-like particles (VLVs) with modified envelope proteins. This parameter change enables longer-lasting immunity while maintaining effectiveness against viral mutations, as the VLV platform allows for stable antigen presentation and sustained immune memory.
Solution Approach 2:
The patent creates composite virus-like particles that combine viral envelope proteins with specific antigens (including SARS-CoV-2 spike protein and HCC markers). This composite structure enables simultaneous induction of neutralizing antibodies and T-cell responses, providing durable and reliable immunity that persists longer than conventional vaccines.
2Reliability
If current HCC treatments (chemotherapy, radiation, liver transplant) are used, then tumor removal is achieved, but high relapse and recurrence rates occur
Solution Approach 1:
The patent employs self-service by using the tumor's own markers (GPC3, HCC markers) as the antigen target. The VLV vaccine presents these self-markers to the immune system, enabling the body's own immune cells to recognize and attack the tumor. This self-service approach eliminates the need for external chemotherapy or radiation, resulting in lower relapse rates and improved long-term survival.
Solution Approach 2:
The virus-like particle acts as an intermediary between the tumor marker and the immune system. The VLV presents HCC-specific markers (GPC3, HCC markers) on its surface, serving as a bridge that enables T-cells and antibodies to specifically target and destroy tumor cells. This intermediary mechanism provides more durable treatment effects compared to direct cytotoxic therapies.
3Reliability
If VLV vectors expressing SARS-CoV-2 or HCC antigens are administered, then robust immune responses are induced, but production complexity increases
Solution Approach 1:
The patent segments the VLV production system into modular components: a standardized VLV platform, separate antigen expression cassettes, and defined production steps. This segmentation allows for flexible combination of different antigens (SARS-CoV-2 spike protein, HCC markers) using the same core VLV production system, reducing overall complexity while maintaining robust immune responses.
Solution Approach 2:
The patent creates a universal VLV platform that can express multiple different antigens (SARS-CoV-2 proteins, HCC markers, GPC3) using the same production system. This multi-functionality eliminates the need for separate vaccine development pipelines for different diseases or variants, simplifying production complexity while maintaining the ability to induce strong, disease-specific immune responses.
Data Source
AI summary
The present disclosure relates to the discovery of compositions and methods for therapeutic immunization for SARS-CoV-2 infections and/or disease(s) associated with expression of Glypican-3 (GPC3), including but not limited to cancers such as hepatocellular carcinoma (HCC). Methods of the disclosure include a method of generating virus like vesicles (VLVs), VLVs comprising SARS-CoV-2 antigens from a high titer VLV producing vector, VLVs comprising GPC3 antigens from a high titer VLV producing vector, methods of treating, ameliorating, and/or preventing SARS-COV-2 infection, methods of inducing a memory T and B cell immune response against SARS-CoV-2 infection in a, methods of treating, ameliorating, and/or preventing GPC3 associated disease, and methods of inducing a memory T and B cell immune response against GPC3 in a subject. Furthermore, the disclosure encompasses a pharmaceutical composition for vaccinating a subject to protect the subject against infection with