Lentiviral Vector Encoding LMP1-IPS1 Fusion Protein for STING Activation
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Solution Overview
Problem
Current vaccines, particularly those inducing antibody-based immune responses, are ineffective or unsafe for diseases like HIV and cancer, and fail to elicit strong cellular immune responses necessary for combating cancer and infectious agents that evade the immune system.
Innovation Solution
Development of viral vectors encoding genetic adjuvants, specifically a fusion protein combining the transmembrane portion of the latent membrane protein 1 (LMP1) of Epstein Barr virus with human IPS1, which activates the STING pathway, to enhance cellular immune responses, integrated into a single lentiviral vector for improved immune response induction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If classical vaccines based on antibody-based immune response are used, then eradication of certain infectious diseases is achieved, but they are ineffective or unsafe for diseases like HIV and cancer
Solution Approach 1:
The patent changes the fundamental parameter of immune response type from antibody-based (humoral immunity) to cellular-based (cell-mediated immunity) by using viral vectors that express antigens directly in host cells, making the vaccine effective for diseases like HIV and cancer that require cellular immunity rather than antibody immunity
Solution Approach 2:
The viral vector platform provides universality by being able to deliver antigens for multiple different diseases (HIV, cancer, infectious diseases) through a single technology platform, allowing the same vector system to be adapted for prophylactic and therapeutic applications across different disease indications
2Reliability
If conventional adjuvants like aluminum salts are used, then vaccine effectiveness is improved, but cellular immune response enhancement is poor
Solution Approach 1:
The patent uses viral vectors as an intermediary carrier that delivers antigen genes into host cells, which then express the antigens endogenously and present them through MHC molecules, thereby mediating strong cellular immune responses that conventional adjuvants cannot achieve
Solution Approach 2:
The vaccine combines multiple elements (viral vector platform, antigen genes, and genetic adjuvants encoding immune regulatory molecules) into a composite immunotherapeutic product that simultaneously provides antigen delivery, immune stimulation, and cellular response enhancement
3Object-generated harmful factors
If viral vectors encoding genetic adjuvants are used, then cellular immune response is enhanced, but vector complexity increases
Solution Approach 1:
The patent merges the antigen delivery function and genetic adjuvant function into a single viral vector construct, where the vector simultaneously delivers both the antigen gene and the adjuvant gene (encoding immune regulatory molecules), simplifying the overall vaccine architecture while maintaining enhanced cellular immune response
Data Source
AI summary
Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens and an adjuvant, and optionally may encode one or more soluble checkpoint inhibitor molecules. The adjuvant is a fusion protein including latent membrane protein 1 (LMP1) from Epstein Barr virus with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.