Viral Genomic and Vaccination / Introduction
The Viral Genomics and Vaccination laboratory was created in January 2006 within the Department of Virology of the Institut Pasteur and transformed into a Unit in 2010 with two objectives: (i) to use reverse genetics to develop new live recombinant vaccines based on measles virus, and (ii) to map virus-host protein interactions to identify new therapeutic targets. These approaches are synergistic: reverse genetics of viral vectors is instrumental to investigate the role of protein-protein interactions identified by functional genomics, and the information obtained from virus-host interactions improves the design of vectors. Over the past years, we managed to introduce in clinical trial a measles-HIV vaccine candidate currently in development with GSK. We also generated other vaccine candidates against dengue, WVN, chikungunya, SARS and H5N1 respiratory viruses that were protective in animal models and are at different steps of development in the context of industrial or academic partnerships. In parallel, a large plasmid collection of viral ORFs was established and used to perform yeast two-hybrid screens. This allowed us to identify hundreds of novel protein-protein interactions involved in viral replication and antiviral innate immunity. In particular, we have shown that virulence factors expressed from the P gene of paramyxoviruses target STAT1, STAT2 and Jak1 to block IFN-a/b signaling but also stimulates the MAPK/ERK pathway to promote viral replication. More recently, we have developed alternative strategies to yeast two-hybrid, using either novel protein-binding assays or recombinant virus strains expressing tagged proteins to purify protein complexes directly from infected cells. For the next years, our objective in vaccinology is to take advantage of our previous results and industrial partnerships to further develop and introduce in clinical trials several other vaccine candidates against malaria, dengue and AIDS. Finally, we will take advantage of this information to search for chemical compounds that disrupt essential virus-host interactions and represent antiviral lead compounds.
Our work during the last three years has generated 44 scientific publications, 8 international patents, 3 industrial R&D contracts, 3 European programs, a number of institutional grants and a number of national and international collaborations. The whole team is committed to these projects. Recently M. Sala and N. Escriou, two Institut Pasteur scientists have been integrated into the Unit, which is now composed of 3 CNRS scientists, 2 Institut Pasteur scientists, 4 post-docs, 3 PhD students, 1 engineer, 3 technicians and 1 secretary. This report describes the main progress of the past 5 years activity of UG2V and related future projects.