C-Terminal NHBA Fragment Vaccine for Gonococcal Immune Killing

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Solution Overview

Problem

The emergence of multidrug-resistant strains of Neisseria gonorrhoeae poses a significant challenge in managing sexually transmitted infections, with high prevalence and severe sequelae, and existing vaccines face challenges due to antigenic variation and lack of protective immunity.

Innovation Solution

Administration of a C-terminal fragment of the Neisserial Heparin Binding Antigen (NHBA) protein from Neisseria gonorrhoeae elicits higher levels of bactericidal and opsonophagocytic antibodies, providing an immunogenic response against gonococcal bacteria.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If full-length NHBA protein is used as vaccine antigen, then immunogenicity is provided, but bactericidal and opsonophagocytic killing levels are insufficient compared to C-terminal fragment

Engineering Contradiction:

ImproveimmunogenicityVSAvoidbactericidal and opsonophagocytic killing levels

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The full-length NHBA protein is segmented into a C-terminal fragment (residues 300-426) that contains the critical immunogenic epitopes. This segmentation identifies and isolates the functional region responsible for high-level bactericidal and opsonophagocytic killing, while the N-terminal region (residues 1-299) which does not contribute to protective immunity is discarded.

Inventive Principle:

Principle #1Segmentation

2Productivity

If C-terminal NHBA fragment is used, then bactericidal and opsonophagocytic killing levels are enhanced, but protein expression levels in some gonococcal strains are reduced

Engineering Contradiction:

Improvebactericidal and opsonophagocytic killing levelsVSAvoidNHBA expression levels

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The C-terminal fragment is extracted as a separate immunogenic unit from the full-length protein. This allows the fragment to be produced independently in vaccine formulations, ensuring consistent expression levels regardless of the source strain's overall NHBA expression variability. The extracted fragment maintains its immunogenicity while eliminating the constraint of source strain expression levels.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If NHBA protein is used as vaccine, then immune response is elicited, but antigenic variation in N. gonorrhoeae surface structures complicates vaccine development

Engineering Contradiction:

Improveimmune responseVSAvoidantigenic variation

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The C-terminal fragment contains localized conserved epitopes that are critical for protective immunity against N. gonorrhoeae. By focusing the vaccine on this specific local region rather than the entire surface proteome, the vaccine targets conserved functional elements that are less subject to antigenic variation, thereby maintaining immune response effectiveness across different strains.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS12479892B2Immunogenic protein against gonococcal infection

Publication Date: 2025.11.25 GRIFFITH UNIVERSITY

AI summary

This invention relates, inter alia, to an immunogenic fragment of a Neisserial Heparin Binding Antigen (NHBA) protein of Neisseria gonorrhoeae (SEQ ID NO: 1) for the prevention and treatment of Neisseria gonorrhoeae or gonococcal- or meningococcal-associated diseases and conditions. In some embodiments, the immunogenic fragment corresponds to a C-terminal fragment of the protein (SEQ ID NO: 2).