Molecular Prevention and Therapy of Human Diseases - CNRS URA3012  


  HEADNicole GUISO, PhD / nicole.guiso@pasteur.fr
  MEMBERSOffice staff: LANGLAIS Laurence (laurence.langlais@pasteur.fr) VEILLAULT Sophie (50%) (sophie.veillault@pasteur.fr)
Researchers: GUISO Nicole, Head of the Institut Pasteur Research Unit (PTMMH), Director of the National Reference Centre of Whooping cough and others bordetelloses and Director of the National Reference Centre of Toxinogenic Corynebacteria; nicole.guiso@pasteur.fr BEDOUELLE Hugues, Director of the CNRS Research Unit URA3012; hugues.bedouelle@pasteur.fr
Scientific trainees: ABACHE Toufik Post-doctoral researcher - until 08/2010 PETIT TOPIN Isabelle Post-doctoral researcher - until 10/2010 RHAYAT Lamya Post-doctoral researcher - until 12/2010 OULD ABEIH Mohamed Doctoral student - Paris VII - until 09/2012 mohamed.ould-abeih@pasteur.fr ZIDANE Nora Doctoral student - Paris VII - until 09/2013 nora.zidane@pasteur.fr FARFOUR Eric Master student-MD until 09/2011 eric.farfour@pasteur.fr
Other personnel : GUILLOT Sophie Engineer, Vice-director of the National Reference Centre of whooping cough and others bordetelloses – sophie.guillot@pasteur.fr BADELL-OCANDO Edgar Engineer, Vice-director of the National Reference Centre of Toxigenic corynebacteria- edgar.badell-ocando@pasteur.fr HEGERLE Nicolas Engineer (under contract)- nicolas.hegerle@pasteur.fr NJAMKEPO Elisabeth Engineer (50% Research - 50 % NRC) – elisabeth.njamkepo-nguemkam@pasteur.fr PARIS Anne-Sophie Engineer (under contract)- anne-sophie.paris@pasteur.fr BRUN Delphine Technician (50% Research - 50 % NRC) - delphine.brun@pasteur.fr DORE Gregory Technician (50% Research - 50 % NRC) – gregory.dore@pasteur.fr ZIDANE Nora Technician (under contract) - nora.zidane@pasteur.fr POURADIER Nadine Preparation laboratory (50%) – nadine.pouradi@pasteur.fr DENIZON Mélanie Preparation laboratory (50%) – melanie.denizon@pasteur.fr SIMONEAU Elsa Preparation laboratory (50%) - elsa.simoneau@pasteur.fr NGUYEN Huu Huan Preparation laboratory (50%) - huu-huan.nguyen@pasteur.fr


  Annual Report

The main objective of our unit is to evaluate the consequences of extensive vaccination of human populations on the microbe targeted by the vaccine, the bacterial ecosystem and the human population in order to propose adapted strategies of prevention and new therapeutic tools to face some of these consequences.

Our unit harbours the National Centre of Reference for Whooping Cough and other bordetellosis http://www.pasteur.fr/sante/clre/cadrecnr/bordet-index.htmland theNational Centre of Reference for toxigenic corynebacteria .http://www.pasteur.fr/sante/clre/cadrecnr/coryndipht-index.html

The Bordetella teamstudies the bacterial determinants involved in the pathogenicity of the bacteria from the Bordetellagenus, the regulation of the expression of these determinants, the immune responses that they induce in the host, human or animal, after infection, the spatio-temporal evolution of the bacteria and the development of new therapeutical and diagnostic tools. The major observations of 2010 were the influence of herd immunity induced by vaccination with subunit pertussis vaccines, in the control of the virulence of B. pertussis isolates but also B. parapertussisisolates, in contrast to the influence of herd immunity induced by vaccination with whole-cell vaccines.

The Coryne teamhas participated to the development of Multi Locus Sequence Typing technique of C. diphtheriae to replace ribotyping and is currently developing different new identification tools of the species of the diphtheriaecomplex (diphtheriae, ulceransand pseudotuberculosis). Furthermore, we are analyzing the evolution of antibiotic resistances of the corynebacteria of the diphtheriaecomplex.

The protein and antibody engineering teamis studying the mechanisms of neutralization of infectious agents by antibodies at the molecular and atomic levels, and their implications for the development of diagnostic and therapeutic tools. We have undertaken to clarify, through in vitro studies, the complex relations between structure and functions of the Human Ribosomal Protein SA (RPSA), which is a membrane receptor of laminin, prion and re-emerging arboviruses. We have pursued the development of new serological assays for the early serodiagnosis of flavivirus infections, in particular to distinguish between vaccine responses and natural infections. Finally, we have shown that is is possible to create reagentless fluorescent biosensors from any element of natural (e.g. antibodies) or artificial families of antigen binding proteins.

Teaching, training scientists from the net of the Institut Pasteur in order to create National Reference Centres involved in vaccine surveillance, help in case of epidemics and public health activities, were pursued.

Keywords: whooping cough, diphtheria, dengue, vaccines, consequences of vaccination, antibodies, biosensors



  Publications

GUISO N. Bordetella pertussisand pertussis vaccines. Clinical Infectious Diseases. 2009, 49(10):1565-9

BOUCHEZ V, BRUN D, DORE G, NJAMKEPO E, GUISO N. Bordetella parapertussis isolates not expressing pertactin circulating in France Clin Microbiol Infect2010 DOI: 10.1111/j.1469-0691.2010.03303.x

BOLT F, CASSIDAY P, TONDELLA ML, DE ZOYSA A, EFSTRATIOU A, SING A, ZASADA A, BERNARDS K, GUISO N, BADELL-OCANDO E, ROSSO ML, BALDWIN A, DOWSON C. Multilocus sequence typing identifies evidence for recombination and two distinct lineages for Corynebacterium diphtheriaJ Clin Microbiol. 2010 48(11): 4177-4185

HERSHKOVITZ, O, ROSENTAL, B, ROSENBERG L A, NAVARRO-SANCHEZ ME, JIVOV S, ZILKA A, GERSHONI-YAHALOM, O, BRIENT-LITZLER, E, BEDOUELLE H, HO JW, CAMPBELL KS, RAGER-ZISMAN B, DESPRES P, PORGADOR A, NKp44 receptor mediates interaction of the envelope glycoproteins from the West Nile and dengue viruses with NK cells. Journal of Immunology,2009, 183, 2610-2621

TAWAR, R. G., DUQUERROY, S, VONRHEIN, C, VARELA, P. F, DAMIER-PIOLLE, L, CASTAGNÉ, N, MACLELLAN, K, BEDOUELLE, H, BRICOGNE, G, BHELLA, DELÉOUËT, J.-F, REY FA. X-ray structure of a Respiratory Syncytial Virus Nucleoprotein-RNA template-like assembly. Science, 2009, 326, 1279-1283



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Activity Reports 2010 - Institut Pasteur
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