Replication-Deficient MCMV Vector for Non-Mouse Immunity

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Solution Overview

Problem

Current vaccines face challenges in inducing robust and lasting antigen-specific immune responses, particularly due to limitations in re-usability and safety concerns related to vector-specific neutralizing antibodies, which restrict their application against multiple infectious diseases and cancers.

Innovation Solution

A replication-deficient murine Cytomegalovirus (MCMV) vector with a disrupted immediate-early 2 (ie2) gene is used to induce antigen-specific immune responses in non-mouse subjects, offering a safer and more effective alternative by expressing disease antigens without replicating in human cells, thus avoiding immune priming and providing long-term immunity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a replication-competent viral vector is used to induce immune response, then the immune response is robust, but safety concerns arise due to potential disease manifestations and immune priming

Engineering Contradiction:

Improveimmune response robustnessVSAvoiddisease manifestations

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The viral vector genome is segmented into essential replication genes and non-essential genes. The ie2 gene is selectively deleted to create replication deficiency in non-murine cells while preserving immune-stimulating capabilities. This segmentation allows the vector to maintain immunogenicity without full replication competence, resolving the contradiction between robust immune response and safety.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The vector exhibits differential replication properties in different host species: it is replication-competent in murine cells but replication-deficient in non-murine cells due to species-specific requirements for the IE2 protein. This local quality variation allows the same vector to provide robust immune stimulation while being safe for human and veterinary use.

Inventive Principle:

Principle #3Local quality

2Object-affected harmful factors

If a replication-deficient viral vector is used to ensure safety, then disease manifestations are avoided, but the immune response may be insufficient or short-lived

Engineering Contradiction:

Improvesafety from disease manifestationsVSAvoidduration of immune response

Core Design Contradiction:

Object-affected harmful factorsVSDuration of action of moving object

Solution Approach 1:

The replication status of the viral vector is changed as a key parameter: the vector is engineered to be replication-deficient in non-murine cells through ie2 gene deletion. This parameter change ensures safety by preventing disease manifestations while the vector still provides sufficient immune stimulation for robust and lasting immunity through alternative mechanisms.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If conventional vaccines requiring prime/boost protocols are used, then adequate immune response can be achieved, but delivery logistics and compliance become problematic

Engineering Contradiction:

Improveimmune response adequacyVSAvoidvaccination protocol complexity

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The vector is pre-engineered with optimized immunogenic properties through selective gene deletion (ie2) that enhances its ability to stimulate immune responses. This preliminary action allows the vector to achieve adequate immune response with a single administration, eliminating the need for complex prime/boost protocols and improving ease of operation.

Inventive Principle:

Principle #10Preliminary action

4Reliability

If adenovirus-based vaccines are used, then robust immune protection is achieved, but re-usability is limited due to vector-specific neutralizing antibodies

Engineering Contradiction:

Improveimmune protectionVSAvoidre-usability against multiple targets

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The MCMV vector platform is designed with universal applicability: by using a replication-deficient design that does not elicit strong neutralizing antibody responses, the same vector type can be reused to deliver different disease antigens for multiple infectious diseases and cancers, unlike adenovirus vectors that become ineffective after initial exposure.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250092421A1A murine cytomegalovirus vaccine vector for administration in a non-mouse subject

Publication Date: 2025.03.20 HELMHOLTZ ZENTRUM FUER INFEKTIONSFORSCHUNG GMBH

AI summary

The invention relates to a replication-deficient murine Cytomegalovirus (MCMV) vector for use in inducing an antigen-specific immune response in a subject, wherein the subject is not a mouse, and wherein said vector expresses a disease antigen. The invention further relates to a pharmaceutical composition comprising a replication-deficient murine Cytomegalovirus (MCMV) vector suitable to induce an antigen-specific immune response in a subject, wherein said vector expresses a disease antigen, and wherein the composition is configured for administration to a non-mouse subject. In embodiments, the vector has a disrupted immediate-early 2 (ie2) gene causing a replication deficiency of said vector in a non-mouse subject. The invention further relates to a pharmaceutical composition for use in inducing an antigen-specific immune response in a non-mouse subject to the expressed disease antigen.