HBV-Specific T Cell Response via MHC-E CMV Vector Engineering

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current immunotherapies for chronic hepatitis B virus (HBV) infection struggle to overcome T cell immunotolerance and consistently achieve lasting reversal of T cell exhaustion or sustained viral suppression, exacerbated by the lack of physiologically relevant animal models.

Innovation Solution

Administering a cytomegalovirus (CMV) vector expressing HBV antigens without active UL128, UL130, UL146, and UL147 proteins to elicit a CD8+ T cell response, utilizing MHC-E restriction to generate a unique set of T cell responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional immunotherapies are used to treat chronic HBV infection, then T cell immunity is stimulated, but T cell immunotolerance and exhaustion prevent lasting viral suppression

Engineering Contradiction:

Improvelasting viral suppressionVSAvoidT cell immunotolerance

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses MHC-E as an intermediary pathway to present HBV antigens to CD8+ T cells. By utilizing the MHC-E restriction system, the invention creates a novel immunological pathway that bypasses the exhausted conventional MHC-I restricted T cell responses, enabling effective viral suppression without triggering immunotolerance

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the MHC restriction parameter of the T cell response by focusing on MHC-E restricted epitopes rather than conventional MHC-I epitopes. This parameter change allows the generation of robust CD8+ T cell responses that are functional in chronic infection settings where conventional pathways have failed

Inventive Principle:

Principle #35Parameter changes

2Productivity

If CMV vector is used to express HBV antigens, then robust T cell response is generated, but UL128-UL147 proteins may interfere with MHC-E presentation

Engineering Contradiction:

ImproveT cell response magnitudeVSAvoidMHC-E interference by UL proteins

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and removes the problematic UL128, UL130, UL146, and UL147 genes from the CMV vector. This extraction eliminates the harmful interference these proteins cause with MHC-E presentation, while preserving the beneficial robust T cell response generation capability of the CMV vector system

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent converts the potential harm of CMV UL proteins into benefit by selectively removing only the interfering UL128-UL147 genes while retaining the CMV vector's strong antigen expression and T cell stimulatory capabilities. This creates an optimized vector that maintains productivity without the harmful side effects

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS12599658B2Hepatitis B virus-specific T cell responses

Publication Date: 2026.04.14 OREGON HEALTH & SCI UNIV

AI summary

The present disclosure relates to methods to generate an immune response for the treatment or prevention of hepatitis B virus infection. This disclosure also relates to methods to generate MHC-E and/or MHC-II restricted CD8+ T cells for the treatment or prevention of hepatitis B virus infection.