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Autochtonous toxigenic Corynebacterium diphtheriae have disappeared in mainland France, but non-toxigenic C. diphtheriae are still circulating. Using phenotypic and molecular tools, we retrospectively characterized 103 non-toxigenic C. diphtheriae collected in mainland France and highlight several changes. The proportion of C. diphtheriae belfanti increased between 1977 and 2011 and it is the most frequent biotype recovered in recent years. Resistance to ciprofloxacin has increased and most isolates with decreased sensitivity belong to the belfanti biotype. Using multilocus sequence typing, we demonstrate that French isolates are distributed in a large number of sequence types and identify three distinct lineages. C. diphtheriae mitis and gravis form lineage I while C. diphtheriae belfanti forms lineages II and III. Almost all isolates of lineage II are part of a unique clonal complex or are very close to it. Most French isolates have a dtxR sequence homologous to that of toxigenic isolates, suggesting that if lyzogenised by a corynephage, they can express diphtheria toxin.

International audience; The potent IFN-gamma inducing fusion antigen Ag8513-ESAT-6 (85136) is a lead subunit candidate to improve current vaccination against Mycobacterium tuberculosis (Mtb). The recombinant M. bovis BCG strain Myc3504 was constructed to secrete 85B6. It was based on commercial BCG strain Moreau Rio de Janeiro (BCG(MoWT)) which remains available for human oral administration. Myc 3504 induced higher levels of 85B6-specific IFN-gamma circulating T-cells as compared to BCG(MowT). A novel needle-free mucosal immunization regimen combining oral prime with Myc3504 or BCG(MoWT) With intranasal boost with LTK-63-adjuvanted 85136 was compared to subcutaneous prime-boost immunization. Strikingly whereas parenteral immunization induced sustained levels of 85B6-specific IFN-gamma secretion by circulating T-cells, rnucosal regimens induced barely detectable IFN-gamma. Despite this, mice and guinea pigs immunized with the mucosal regimens were as efficiently protected against aerosol Mtb challenge as parenterally immunized animals. After Mtb challenge, anti-ESAT-6 IFN-gamma responses sharply increased in non-vaccinated mice as a hallmark of infection. Parenterally immunized mice that controlled Mtb infection, displayed anti-ESAT-6 IFN-gamma responses as high as non-immunized infected mice, compromising the possible use of ESAT-6 as a diagnostic tool. Interestingly, in mucosally immunized mice that were equally protected, post-challenge ESAT-6-specific IFN-gamma T-cell response remained low. (c) 2008 Elsevier Ltd. All rights reserved.

International audience; The widely administered Mycobacterium bovis BCG is an attractive live vector for the development of AIDS vaccines. We explored immune responses induced in cynomolgus macaques tor BCG-SIV3, a mixture of three recombinant BCG strains expressing the SIVmac251 nef, gag and env genes. After a single intradermal (ID) inoculation, circulating blood cells from rBCG-SIV3-vaccinated monkeys exhibited CTL responses targeted against the three antigens and interferon-gamma (IFN-gamma) secretion was observed. A rectal or oral boosting dose of rBCG-SIV3 elicited anti-SIV IgAs in the rectum of vaccinated monkeys and increased IFNgamma secretion by circulating blood cells. Despite a good response against the vector, rBCG-SIV3 administration did not induce IgG antibody responses or lymphoproliferation against the SIV antigens in blood. This could be due to the lack of in vivo persistence of the recombinant BCG strains that were used. Rectal challenge with fully pathogenic SIVmac251-infected all animals. However, after viral challenge, anti-SIV cellular and antibody responses were higher in rBCG-SIV3 monkeys than in controls indicating that the vaccine induced anti-SIV CD4(+) T-cell memory. (C) 2003 Elsevier Ltd. All rights reserved.

Introduction Mayotte est un departement d’outre-mer geographiquement isole, expose au risque de maladies infectieuses et soumis a une forte migration sanitaire en provenance des iles voisines. La diphterie illustre l’importance d’un diagnostic microbiologique de proximite. En 2007, le dernier cas de diphterie ORL a Corynebacterium diphtheriae porteur du gene codant la toxine (tox +) est notifie chez un nourrisson de 2 mois, non vaccine, qui en est decede. L’annee suivante, le laboratoire de l’hopital met en place une procedure pour le diagnostic rapide des suspicions cliniques de diphterie. Materiels et methodes L’analyse porte sur les isolats de C. diphtheriae tox +identifies de 2008 a 2015 en associant microbiologie conventionnelle (milieu de culture specifique de Tinsdal) et biologie moleculaire (amplification du gene tox) avec confirmation secondaire du diagnostic par le CNR. Resultats Sur cette periode, 13 isolats de C. diphtheriae tox+ sont identifies au niveau de lesions cutanees chroniques evoluant depuis des semaines, voire des mois, souvent polymicrobiennes. Parmi ces cas : 10 hommes et 3 femmes, âge median de 11 ans (12 mois-39 ans), 8 cas importes et 7 sans antecedent vaccinal. Les patients ont recu une antibiotherapie adaptee, associee ou non a un geste chirurgical, sans serotherapie en absence de manifestations toxiniques. Le diagnostic par le laboratoire a permis une prise en charge adaptee et la mise en œuvre precoce des mesures de gestion preconisees par les autorites sanitaires pour les contacts (ecouvillonnage nasopharynge, antibioprophylaxie, vaccination ou rattrapage vaccinal). Parmi 168 contacts identifies, l’analyse a permis le diagnostic de 8 cas de portage pharynge asymptomatique dans l’entourage de 4 patients. Il est note que 25 isolats tox− ont egalement ete collectes de lesions cutanees chroniques. Conclusion Des cas de diphterie cutanee tox + surviennent episodiquement a Mayotte. L’absence d’une circulation plus importante de ces bacteries ne peut etre ecartee du fait de la frequence de plaies cutanees surinfectees et des difficultes d’acces aux soins d’une partie de la population. Face a l’insuffisance de couverture vaccinale chez l’adolescent et l’adulte, la poursuite de la surveillance microbiologique de la circulation de C. diphtheriae demeure une priorite.

Mice lacking B- and T cell functions could be made susceptible to the development of the human malaria parasite Plasmodium falciparum by partial depletion of macrophages and substitution of mice erythrocytes by human ones. Both tissue and blood macrophages of mice were found to be crucial in defense against heterologous human infected cells and had to be partially depleted and/or their increase controlled to allow for parasite development. In view of the scarcity of animals able to harbour human parasites, this novel model opens several new perspectives of research as discussed here by Edgar Badell, Valerie Pasquetto, Nico van Rooijen and Pierre Druilhe. It should become particularly useful in the fields of drugs and vaccine design.

In a recent issue of Parasitology Today, Stanley and Virgin1 have stressed the potential of B- and T-cell deficient mice, among which severe combined immunodeficiency (SCID) mice are most frequently used, as models for the study of parasites. One of the most tantalizing prospects has been in the development of liver stages (LS) of human Plasmodium.