OMVac project - Outer Membrane Vesicles (OMVS) from "Vaccinobacter": a Synthetic Biology approach for effective vaccines against infectious diseases and cancer - involves the application of synthetic biology to create a new bacterial strain ("Vaccinobacter") for the production of multivalent vaccines against infectious diseases and cancer. The research project, awarded to Prof. Guido Grandi, University of Trento, has a term of five years and benefits from 2.61 million euro of funding under the Seventh Framework Program of the European Union. Role of TLS is to collaborate on the development of the platform and validation of cancer vaccines, using innovative animal models.
Overview Vaccination is one of the most effective intervention in the history of medicine. Devastating diseases caused by various infectious agents have been completely or almost completely eliminated thanks to the introduction of vaccination practice. However, there are a number of infectious diseases for which vaccines do not exist yet. Furthermore, chronic diseases such as cancer are still awaiting valid solutions to turn vaccination into an effective prophylactic and/or therapeutic intervention. The development of vaccines against recalcitrant infections and cancer will depend on the identification of highly specific antigens to be formulated with potent adjuvants capable of eliciting effective immune responses. The main objective of our Laboratory is to create novel vaccine platforms based on the exploitation of the Outer Membrane Vesicles (OMVs) naturally released by Gram-negative bacteria. Because of the intrinsic capacity of OMVs to potently stimulate innate immunity and thanks to the possibility of OMVs to be manipulated with heterologous antigens the vesicles have the potential to become the scaffold of highly innovative and effective vaccines.
The main project activities can be summarized as follows:
Genome editing of Escherichia coli to create a new strain specialized in OMVs production
OMVs carry a conspicuous number of endogenous proteins mainly belonging to outer membrane and periplasmic compartments. It is expected that the alteration of the protein repertoire of OMVs could profoundly affect the immune response elicited in mammals both in qualitative and quantitative terms. Innovative approaches for genome editing are being applied to selectively remove/add genes and gene pathways to ultimately create an E. coli strain capable of releasing abundant quantities of OMVs carrying a minimal amount of endogenous proteins and novel immune-stimulatory components.
Development of novel genetic tools to decorate OMVs with foreign antigens The main objective of this activity is to develop gene technology strategies to deliver the desired protein antigens to the OMV compartments. Such technologies will include gene fusions, domain engineering and grafting of transport machineries.
Development of novel OMV-based vaccines against bacterial pathogens and cancer OMVs are being decorated with selected bacterial and cancer antigens and immunogenicity and protective activity of OMVs are being evaluated in vitro and in vivo. In particular, the mechanisms of stimulation of innate immunity is being analyzed using cell lines engineered with specific Patterns Recognition Receptors (PRRs). Furthermore, the elicitation of antibodies, CD4 and CD8 T cells will be evaluated in appropriate animal models. Finally, mouse models for infectious diseases and cancer will be set-up and used to establish the protective properties of OMV-based vaccines and to correlate protection to humoral and cell-mediated immunity.
Principal Investigator Guido Grandi, Prof.
Team at University of Trento, CIBIO Elena Caproni, PhD (hosted at TLS) Laura Fantappiè, PhD (hosted at TLS) Luca Frattini, PhD Luisa Ganfini, Dr., PhD student (hosted at TLS) Enrico Enrico Konig, PhD Carmela Irene, PhD Michele, Tomasi PhD student Ilaria Zanella, PhD student Francesca Zerbini, PhD Sabine Isaac, PhD student
Team at Toscana Life Sciences (TLS) Alberto Grandi, PhD Matteo Parri, PhD