Molecular Prevention and Therapy of Human Diseases - URA CNRS 3012  


  HEADDr Nicole GUISO / nguiso@pasteur.fr
  MEMBERSLanglais, Laurence (langlais@pasteur.fr) / Veillault, Sophie (50%) (sophveil@pasteur.fr)
GUISO Nicole, chef d'unité, chef de laboratoire, Director of the Reference National Center of Whooping cough and others bordetelloses, HDR ; nguiso@pasteur.fr / BEDOUELLE Hugues, Directeur de Recherche au CNRS Directeur de la FRE 2849, HDR ; hbedouel@pasteur.fr /ROSSO Marie-Laure, cadre administratif et technique IP, Vice-director of the Reference National Center of whooping cough and others bordetelloses ; mlrosso@pasteur.fr
LISOVA Olesia Post-doctoral researcher, Marie-Curie fellowship then European contract until February 2008 / BRIENT-LITZLER Elodie PhD student - Paris VI - until 10/2008 / BERTINE Mélanie Master 2 - Paris VI - until 30/08/08
BOUCHEZ Valérie - IP Engineer (0.80 %) on contract - vbouchez@pasteur.fr / GUILLOT Sophie – IP Engineer on contract – sguillot@pasteur.fr / NJAMKEPO Elisabeth– IP Engineer (50% Research - 50 % RNC) – enjamkep@pasteur.fr / BRUN Delphine - IP Technician (50% Research - 50 % RNC) - dbrun@pasteur.fr / DORE Gregory – IP Technician (50% Research - 50 % RNC) – gdore@pasteur.fr / CANTINELLI Thomas - IP Technician on contract - cantinel@pasteur.fr / CHENAL-FRANCISQUE Viviane - IP Technician on contract - vchenal@pasteur.fr / POURADIER Nadine – Aide de laboratoire (50%) – npouradi@pasteur.fr / BELHASSEN Chantal - Aide de laboratoire (50%) – cbelhass@pasteur.fr / LEBON Gisèle - Aide de laboratoire (50%) - glebon@pasteur.fr / NGUYEN Huu Huan– Agent de laboratoire (50%) - huuhuan@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 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 harbors the National Center of Reference for Whooping Cough and other bordetellosis http://www.pasteur.fr/sante/clre/cadrecnr/bordet-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 results of 2007 were the confirmation of the temporal evolution of B. pertussispopulation in France with a decrease in genetic material essentially due to loss of genes and pseudogenes, most of them being flanked by insertion sequences. We demonstrated that this evolution has no geographical specificity and does not involve virulence genes. However, herd immunity has an influence on the expression of some of them.Teaching, training scientists from the net of the Institut Pasteur in order to create National Reference Centers involved in vaccine surveillance, help in case of epidemics and public health activities, were pursued.

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 characterize the mechanisms of recognition between a neutralizing monoclonal antibody and the envelope glycoprotein E of dengue virus. The fine mapping of its epitope by site-directed mutagenesis and its transplantation in the E protein of other flaviviruses have enabled us to show that the mapped epitope was complete, discontinuous, specific for the taxonomic group of dengue virus, and overlaping residues involved in infection. We have developed an ELISA assay for the serology of infections by flaviviruses, which is simpler and more specific than the existing assays, and for which all the reagents are produced in bacteria at low levels of biosafety. The assays for dengue virus (4 serotypes), West-Nile virus, yellow fever virus and other flaviviruses are under evaluation with serums of infected patients. We have contributed to the development of a hybrid measle-dengue vaccine. Finally, we have extended the design and construction of reagentless fluorescent biosensors, previously developed for recombinant antibodies, to an artificial family of antigen binding proteins, whose physico-chemical properties (production, solubility, stability) are much more favorable.

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



  Publications

Patents: Bedouelle, H., Brient-Litzler, E., Dussart, P., Despres, P. and Bremand, L. (2007) Method for the diagnosis or the screening of an arbovirus infection, reagents useful in said method and their applications. Application No EP07290749.6; date of priority 15/06/2007; applicants: CNRS, Institut Pasteur.

List of the five publications in the four last years :

GUISO N, NJAMKEPO E, VIE LE SAGE F, ZEPP F, MEYER CU, ABITBOL V, CLYTI N, S CHEVALLIER. (2007) Long-term humoral and cell-mediated immunity after acellular pertussis vaccination compares favourably with whole-cell vaccines 6 years after booster vaccination in the second year of life. Vaccine. 25(8):1390-1397

CARO V., HOT D., GUIGON G., HUBANS C., ARRIVE M., SOUBIGOU G., RENAULD-MONGENIE G., ANTOINE R., LOCHT C. LEMOINE Y., GUISO N. (2006) Temporal analysis of French Bordetella pertussisisolates by comparative whole-genome hybridization. Microbes Infect. 8:2228-2235

CARO V., NJAMKEPO E., VAN AMERSFOORTH S. C.M. , MOOI F. R.,ADVANI A., HALLANDER H.O., HE Q., MERTSOLA J., RIFFELMANN M., VAHRENHOLZ C., VON KÖNIG C.H., GUISO N. (2005) Pulsed-field gel electrophoresis analysis of Bordetella pertussispopulations in various European countries with different vaccine policies. Microbes Infect.7: (7-8) 976-982

LISOVA O., HARDY F., PETIT V., BEDOUELLE H. (2007) Mapping to completeness and transplantation of a group specific, discontinuous, neutralizing epitope in the envelope protein of dengue virus. J. Gen. Virol. 88 : 2387-2397. doi: 10.1099/vir.0.83028-0.

BRANDLER S., LUCAS-HOURANI M., MORIS A., FRENKIEL M.-P., COMBREDET C., FÉVRIER M., BEDOUELLE H., SCHWARTZ O., DESPRÈS P. and TANGY F. (2007) Pediatric measles vaccine expressing a dengue antigen induces durable serotype-specific neutralizing antibodies to dengue virus. PLoS Neglected Tropical Diseases, 1(3):e96



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Activity Reports 2007 - Institut Pasteur
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