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Martine CERUTTI

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A NEW BACULOVIRUS EXPRESSION SYSTEM FOR THE PRODUCTION OF HIGHLY GLYCOSYLATED MULTI-SUBUNIT PROTEINS. Application to the production of antibody, antibody-derived molecules and vaccines.

Summary of the presentation :

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Multi-subunit proteins are involved in many important biological processes. The baculovirus insect cell system is one of the most efficient system to produce such structures. Glycosylation contributes to very subtle modifications of the structure and activity of numerous proteins, thus it seemed important to consider a new baculovirus expression system allowing the production of complex recombinant proteins with a mammalian complex glycosylation.

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This new system combines the generation of stable multi-recombinant baculoviruses and the production of proteins with "à la carte" glycannic patterns, from simple insect-type glycans to complex-type glycans such as galactosylated and sialylated glycans. In a very original way, all genes are integrated into different individual locus thus contributing to the stability of the resulting multi-recombinant virus which can then be used for large-scale production. The integration of all genes is carried out by homologous recombination - in a single step - into the insect cell.

 

This technology could be used to construct multi-recombinant baculoviruses for the production of complex proteins such as antibodies, antibody-derived molecules and virus-like-particles (VLP). It is then possible to modulate the effector activities of antibodies by optimizing the structure of glycans linked to their constant domain. Glycosylation may also be of a great interest in the design of vaccines. Several vaccines produced in the baculovirus system have already been approved by FDA and EMA. Many scientific reports have also demonstrated that, in contrast with subunit vaccines, injection of recombinant VLPs led to the induction of cellular and humoral responses even in the absence of adjuvant.

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Professional background :

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- Emeritus Director of Research at CNRS.

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- PhD in Virology (1986, Rouen University) and Diploma in Virology at Pasteur Institute (Paris).

Team leader of « Biologie cellulaire et moléculaire » group at Station de Pathologie Comparée, in Saint Christol Lès Alès from 1997 to 2004. Director of “Baculovirus and therapy” unit, CNRS UPS3044, Saint Christol Lès Alès from 2007 to 2019.

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- Basic research on the replication of insect viruses (polyDNAviruses, baculoviruses)

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- Valorization : Setting up of a Technological Platform for the development of original and proprietary technologies for the production of recombinant proteins using the baculovirus/insect cell system i.e. humanisation of glycosylation of recombinant proteins and development of new approaches for the production of recombinant vaccines.

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- Teacher in Master II of Virology, Biotechnology, Immunology, at University of Montpellier, University of Aix-Marseille and Saint Joseph University, Beyrouth, Lebanon.

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- Founding member of « QUARES » association (Qualité en recherche) and participation to the organization of summer schools «  Ecole interorganisme pour la qualité en recherche » (2004-2007).

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- Member of LabEx MAbimprove steering commitee from 2011 to 2018.

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