Attenuated Salmonella Vaccine Vector for Chlamydia

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Solution Overview

Problem

Current vaccines for Chlamydia trachomatis have shown limited effectiveness and safety concerns, with no vaccine advanced into Phase I clinical trials in over 40 years, despite efforts to develop an effective vaccine against Chlamydial infections and associated conditions like trachoma.

Innovation Solution

Development of attenuated Salmonella microorganisms with mutations in SPI-2 genes and aromatic compound biosynthesis genes, expressing immunogenic Chlamydial peptides like PmpG, Pmpl, MOMP, PmpD, PmpH, OmcB, OmpH, and HtrA proteins, to induce an effective immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If attenuated Salmonella microorganisms are used as vaccine vectors, then immune response effectiveness is improved, but safety concerns arise due to potential pathogenicity

Engineering Contradiction:

Improvevaccine effectivenessVSAvoidpathogenicity risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the harmful pathogenicity of Salmonella into a beneficial vaccine platform by using the bacterium's natural ability to invade and replicate within host cells. The attenuated strains, while less virulent, maintain sufficient intracellular presence to effectively present Chlamydia antigens to the immune system, transforming a potential harm into a useful immunological stimulus

Inventive Principle:

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

Solution Approach 2:

The patent applies parameter changes by modifying the Salmonella strain through attenuation mutations that reduce virulence while preserving immunogenicity. Specific genetic modifications alter the bacterium's parameters (virulence factors, replication rate) to achieve an optimal balance between safety and effectiveness as a vaccine vector

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If multiple Chlamydia antigens are expressed in the vaccine vector, then broad protection is improved, but device complexity increases

Engineering Contradiction:

Improvebroad protectionVSAvoidvaccine construct complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent applies universality by designing a single Salmonella vaccine vector that can simultaneously express multiple different Chlamydia antigens (PmpG, PmpH, MOMP, OmcB). This multi-functional platform provides broad protection against different Chlamydia serovars and strains through one vaccine administration, eliminating the need for multiple separate vaccines

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent merges multiple antigen expression cassettes into a single vaccine construct within the Salmonella vector. Different Chlamydia antigens are combined in one bacterial platform, simplifying administration while maintaining the complexity of providing multi-serovar protection

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS8703153B2Salmonella vectored vaccines against Chlamydia and methods of use

Publication Date: 2014.04.22 PROKARIUM LTD

AI summary

The invention provides an attenuated Salmonella vaccine vector comprising one or more heterologous polynucleotides that encode immunogenic Chlamydial peptides. In one embodiment, the attenuated Salmonella vaccine vector comprises aroC and ssaV attenuating mutations. The heterologous polynucleotides encoding the immunogenic Chlamydial peptides can be under the control of an inducible promoter such as a Salmonella ssaG promoter. In one embodiment of the invention, the immunogenic Chlamydial peptide is a PmpG peptide, for instance, a CT110, CT84 or CT40 peptide.