HVEM Agonist Immunization for Enhanced HSV ADCC Responses

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Solution Overview

Problem

Existing HSV vaccines fail to provide effective protection against HSV-1 and HSV-2 infections and latency, with a focus on neutralizing antibody responses that may skew away from antibody-dependent cell-mediated cytotoxicity (ADCC), necessitating a method to enhance ADCC responses for improved immunogenicity and protection.

Innovation Solution

Administering herpesvirus entry mediator (HVEM) agonists or tumor necrosis factor superfamily-14 (TNFSF-14) agonists to enhance ADCC antibody responses over neutralizing antibody responses, potentially through the use of vaccines like ΔgD-2, which induce high-titer ADCC antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If vaccines target glycoprotein D to elicit neutralizing antibody responses, then protection against primary infection is improved, but ADCC responses are suppressed

Engineering Contradiction:

Improveprotection against primary infectionVSAvoidsuppression of ADCC responses

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The vaccine design segments the viral antigens by deleting the gD gene from HSV-2, separating the neutralizing antibody function from the ADCC suppression function. This allows the vaccine to elicit neutralizing antibodies without the concurrent suppression of ADCC responses that occurs with gD-targeting vaccines

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The gD gene is extracted and removed from the HSV-2 vaccine construct. This extraction eliminates the immunomodulatory effect of gD that skews the immune response away from ADCC, while preserving other viral antigens that can stimulate protective immunity through other mechanisms

Inventive Principle:

Principle #2Taking out (Extraction)

2Quantity of substance

If adjuvanted subunit vaccines targeting gD are used, then neutralizing antibody titers are increased, but protection against latency and recurrence is reduced

Engineering Contradiction:

Improveneutralizing antibody titersVSAvoidprotection against latency and recurrence

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

Instead of using gD as the vaccine antigen to elicit neutralizing antibodies, the invention inverts the approach by deleting gD from the vaccine. This allows the immune system to respond to other viral antigens that do not suppress ADCC, thereby achieving protection against latency and recurrence through enhanced ADCC responses rather than neutralizing antibodies

Inventive Principle:

Principle #13The other way round (Inversion)

3Reliability

If vaccines focus on eliciting neutralizing antibody responses, then seroconversion is achieved, but ADCC-mediated protection is compromised

Engineering Contradiction:

ImproveseroconversionVSAvoidcompromised ADCC-mediated protection

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The vaccine creates local quality differences in the immune response by selectively eliminating gD, which is responsible for suppressing ADCC. This allows other regions of the viral antigens to stimulate the immune system in ways that promote ADCC, creating a localized enhancement of ADCC-mediated protection while maintaining overall immunogenicity

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250276039A1Method of enhancing antibody-dependent cell-mediated cytotoxicity (ADCC)

Publication Date: 2025.09.04 ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIV

AI summary

Methods of preferentially enhancing in a subject an antibody-dependent cell-mediated cytotoxicity (ADCC) antibody response over a neutralizing antibody response to a vaccine for an infectious agent using herpesvirus entry mediator (HVEM) agonists, and related compositions.