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  • Periodic Report Summary 2 - OMVAC (Outer Membrane Vesicles (OMVs) from “Vaccinobacter”: A Synthetic Biology approach for effective vaccines against infectious diseases and cancer)

OMVAC Report Summary

Project ID: 340915
Funded under: FP7-IDEAS-ERC
Country: Italy

Periodic Report Summary 2 - OMVAC (Outer Membrane Vesicles (OMVs) from “Vaccinobacter”: A Synthetic Biology approach for effective vaccines against infectious diseases and cancer)

Executive Summary
The main objective of the OMVac project is to apply Synthetic Biology to create a new bacterial species, Vaccinobacter, devoted to the production of multivalent, highly effective vaccines against infectious diseases and cancer.
The project is organized in four main activities: 1) remodeling of E. coli genome to create “Vaccinobacter”, a “living factory” of OMVs deprived of all unnecessary components but carrying the relevant immune potentiators, 2) characterization and optimization of the immune stimulatory properties of OMVs, 3) development of novel methods to incorporate foreign antigens into Vaccinobacter-derived OMVs, 4) loading of OMVs with selected pathogen- and cancer-derived antigens and demonstration of their protective efficacy in appropriate animal models.
The main results and achievements can be summarized as follows:
Activity 1
The proteome of OMVs from the Vaccinobacter progenitor has been defined by using bioinformatics tools and Mass Spectrometry. The list of OMV proteins has been prioritized on the basis of their predicted “dispensability” and abundancy.
An extremely efficient protocol for genome editing has been set-up. The protocol allow the isolation of single and double gene deletions in two working days.
The genome editing protocol is currently being used for the construction of Vaccinobacter whose creation is expected to be completed by the end of 2017.
Activity 2
Cell-based assays for the dissection and quantitation of OMV agonistic activities on different innate immunity receptors have been set-up.
The assays are currently being used for to study the adjuvanticity properties of OMVs purified from the Vaccinobacter progenitor and the mutants that are being generated by Syntheic Biology. A relevant result so far obtained is that, when heterologous antigens are expressed in a particular configuration in specific mutants the reactogenicity of OMVs is drastically reduced but their adjuvanticity properties is largely maintained. The result is expected to be particularly relevant for the use of Vaccinobacter-derived OMVs as pediatric vaccines.
Activity 3
Several strategies have been devised to decorate OMVs with heterologous antigens. They include: 1) the expression of heterologous proteins to allow their compartmentalization in the lumen of OMVs; 2) the expression of heterologous antigens in specific configurations that allow their compartmentalization in the membrane of OMVs; 3) the fusion of heterologous antigens to the C-terminus of different surface-exposed proteins so as to deliver the antigens to the surface of OMVs.
Several bacterial and cancer antigens have been successfully expressed using the above strategies and OMVs decorated with such antigens have been shown to elicit potent antigen-specific immune responses in animal models.
Activity 4
OMVs decorated with Group A Streptococcus and Staphylococcus aureus antigens are being tested in mouse models to evaluate the protective activity the OMV-based vaccines.
Preliminary data using a Group A Streptococcus mouse challenge model indicate that the OMV vaccines confer close to 100% protection.
OMV decorated with several cancer antigens/epitopes are being tested for immunogenicity and protection in immunocompetent cancer mouse models. The data so far accumulated indicate that the OMV-based cancer vaccines are capable of conferring robust protection in different mouse models and can be considered a valid platform for personalized cancer immunotherapy.

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