Institut Pasteur (FR) Nathalie Winter

Institution and Expertise
The Pasteur Institute is one of the world leading research center for infectious diseases. It houses 100 research units and close to 2700 people, including 500 permanent scientists and another 600 scientists visiting from 70 countries annually. The BCG Laboratory & Mycobacterial Genetics is composed of microbiologists and geneticists having long experience in Molecular Biology of mycobacteria. They have developed major genetic tools that are largely used by laboratories involved in mycobacterial research to perform allelic exchange in M. tuberculosis complex and expression of heterologous antigens in M. tb complex. This group is also experienced in recombinant BCG strains development and study of immune responses induced in small animal models This laboratory possesses all equipment for molecular biology experiments, cell cultures and immunology tests, as well as level 2 containment laboratories to perform experiments with rBCG strains.

Personnel involved
Brigitte Gicquel (Professor) is head of the laboratory. Brigitte Gicquel was a member of IMMYC, the WHO Steering Committee responsible for coordination of research on the immunology of tuberculosis and leprosy. She was of the Member of the Expert Panel of Tuberculosis Research Unit of N.I.H. secretariat for cooperation of the foreign office.
Nathalie Winter (Assistant professor) has constructed several rBCG strains expressing genes from various pathogens (including SIV/HIV) as well as reporter genes. She has long experience in mycobacterial expression vectors and immune responses induced in the mouse model.
Micheline Lagranderie (Assistant researcher) has outstanding expertise in BCG and study of immune responses induced by BCG and recombinant BCG strains in the mouse model both after parenteral and mucosal delivery. She will test immune responses induced by the various BCG strains which will be constructed during this project.
One postdoc to be recruited: with expertise in molecular biology and microbiology

Ongoing projects and previous collaboration
Brigitte Gicquel has participated in several European community projects since 1993 and is coordinator for a BIOMED project and a Framework V 'TB Vaccine Cluster' project, both of which also involve Dr McFadden (Partner No1). Professor Gicquel has hosted many international scientists in her laboratory, including Dr Luciana Leite (Partner No3) and Dr Angel Catladi (Partner No5).

Publications/patents
1. N. Winter, M. Lagranderie, S. Gangloff, C. Leclerc, M. Gheorghiu and B.Gicquel (1995) Recombinant BCG strains expressing the SIVmac251nef gene induce proliferative and CTL responses against NEF synthetic peptides in mice .Vaccine, 13, 471-478.
2. J.M. Reyrat, G. Ramirez-Lopez, C. Ofredo, B. Gicquel and N. Winter (1996) The urease activity does not contribute dramatically to the persistence of Mycobacterium bovis bacillus Calmette-Guérin. Infect. Immun., 64, 3934-3936.
3. E.M. Lim, M. Lagranderie, R. Legrand, J. Rauzier, M. Gheorghiu, B. Gicquel and N. Winter (1997) Recombinant Mycobacterium bovis-BCG producing the N-terminal half of SIVmac251 Env antigen induces neutralizing antibodies and cytotoxic T lymphocyte responses in mice and guinea pigs AIDS Res. and Hum. Retrovir. , 13, 1573-1581.
4. M. Lagranderie, N. Winter, Balazuc, A.M., Gicquel,B. and Gheorghiu, M. (1998) : A cocktail of Mycobacterium bovis BCG recombinants expressing the SIV Nef, Gag and Env antigens induces antibody and cytotoxic responses in mice vaccinated by different mucosal routes. AIDS Res and Human Retrovir., 14, 1625-1633
5. Berthet, F.X., M. Lagranderie, P. Gounon, C. Laurent-Winter, D. Ensergueix, P. Chavarot, F. Thouron, E. Maranghi, V. Pelicic, D. Portnoi, G. Marchal, and B. Gicquel (1998) : Attenuation of virulence by disruption of the Mycobacterium tuberculosis erp gene. Science. 282 : 759-762