Utilisation des vecteurs viraux dans l'immunothérapie antitumorale

Les virus sont des outils très intéressants pour délivrer du matériel génétique dans les cellules qu'ils infectent ; c'est pourquoi la thérapie génique les a vite adoptés pour de nombreuses applications, notamment dans la lutte contre les cancers. L'immunothérapie consiste en la stimulation du système immunitaire pour lutter contre une maladie. Différentes stratégies utilisant des vecteurs viraux ont été entreprises : induire une réponse immunitaire anticancéreuse spécifique, moduler la réponse immunitaire, ou encore associer l'immunothérapie à d'autres thérapeutiques comme la virothérapie ou la thérapie monoclonale. L'utilisation des vecteurs viraux dans l'immunothérapie antitumorale est un domaine de recherche encore au stade des essais cliniques animaux et humains. L'objet de cette thèse est de faire un état des lieux sur l'utilisation des vecteurs viraux dans les stratégies d'immunothérapie antitumorale

Antimicrobial susceptibility monitoring of Mycoplasma hyopneumoniae isolated from seven European countries during 2015-2016

Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia, a chronic respiratory disease, causing significant economic losses. Results from the 2015-2016 MycoPath pan-European antimicrobial susceptibility monitoring survey of M. hyopneumoniae are presented. In total, 147 M. hyopneumoniae porcine isolates from Belgium, France, Germany, Great Britain, Hungary, Italy, and Spain were tested. One isolate per farm was retained from pigs that had not been recently treated with antimicrobial agents. The minimal inhibitory concentration (MIC) of 13 antimicrobial agents was determined in a central laboratory using a broth microdilution method, with Friis Medium, incubated at 35 +/- 1 degrees C for 5-12 days. M. hyopneumoniae NCTC 10110 was used as Quality Control. MIC50/MIC90 (mg/L) values were: enrofloxacin 0.06/1; marbofloxacin 0.06/2; spiramycin 0.06/0.25; tulathromycin <= 0.001/0.004; gamithromycin 0.06/0.5; tylosin 0.016/0.06; tilmicosin 0.06/0.5; florfenicol 0.5/1; doxycycline 0.25/1; oxytetracycline 0.25/2; lincomycin 0.06/0.25; tiamulin 0.016/0.06 and valnemulin <= 0.001/0.004. Compared with the data from 2010 to 2012 MycoPath study (50 isolates), MIC50/90 results were similar and the majority were within +/- two dilution steps, except for the MIC50 of oxytetracycline which is more than two dilution steps higher in the present study. Between-country comparisons show some differences in the MIC values for the fluoroquinolones, tulathromycin and tylosin, but the limited sample size per country precludes performing meaningful country comparisons for several countries. Standardized laboratory methods and interpretive criteria for MIC testing of veterinary mycoplasmas are clearly needed; there are currently no clinical breakpoints available to facilitate data interpretation and correlation of MICs with in vivo efficacy

Utilisation des vecteurs viraux dans l'immunothérapie antitumorale

Les virus sont des outils très intéressants pour délivrer du matériel génétique dans les cellules qu'ils infectent ; c'est pourquoi la thérapie génique les a vite adoptés pour de nombreuses applications, notamment dans la lutte contre les cancers. L'immunothérapie consiste en la stimulation du système immunitaire pour lutter contre une maladie. Différentes stratégies utilisant des vecteurs viraux ont été entreprises : induire une réponse immunitaire anticancéreuse spécifique, moduler la réponse immunitaire, ou encore associer l'immunothérapie à d'autres thérapeutiques comme la virothérapie ou la thérapie monoclonale. L'utilisation des vecteurs viraux dans l'immunothérapie antitumorale est un domaine de recherche encore au stade des essais cliniques animaux et humains. L'objet de cette thèse est de faire un état des lieux sur l'utilisation des vecteurs viraux dans les stratégies d'immunothérapie antitumorale.TOULOUSE-EN Vétérinaire (315552301) / SudocTOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Efficacy and Safety of 4.7 mg Deslorelin Acetate Implants in Suppressing Oestrus Cycle in Prepubertal Female Dogs

Our multicentric, masked, controlled and randomised study aimed to assess the efficacy and safety of Suprelorin&reg; 4.7 mg (Virbac, Carros, France) regarding oestrus prevention in prepubertal intact bitches. Twelve- to eighteen-week-old females (n = 83) were allocated either a deslorelin implant (n = 62) or 0.9% sodium chloride (n = 21) group. Clinical assessment (heat signs), 17&beta; oestradiol and progesterone assays, and vaginal cytology were performed at day (D)0, D7, D21, month (M)3 and M6 after product administration, and were then performed every other month until reaching puberty. Trained owners assessed heat signs between each veterinary visit. All bitches (n = 83) reached puberty before M30. Deslorelin significantly extended the median time to sexual maturity when compared to the control group (377 days versus 217 days after D0, p &lt; 0.0001). Three females, implanted between 16 and 18 weeks of age, expressed an induced oestrus. Additional descriptive data, collected over a 24 month-period, showed functional reproductive abilities in both deslorelin (n = 52) and control (n = 21) groups once puberty was achieved. In conclusion, Suprelorin&reg; 4.7 mg seems to be an effective and safe option for postponing the onset of oestrus when administered to prepubertal female dogs aged from 12 to 16 weeks

Antimicrobial susceptibility of nine udder pathogens recovered from bovine clinical mastitis milk in Europe 2015–2016: VetPath results

International audienceVetPath is an ongoing pan-European antimicrobial susceptibility monitoring programme collecting pathogens from diseased cattle, pigs and poultry not recently treated with antibiotics. Non-duplicate isolates (n = 1244) were obtained from cows with acute clinical mastitis in eight countries during 2015-2016 for centrally antimicrobial susceptibility testing according CLSI standards. Among Escherichia coli (n = 225), resistance was high to ampicillin and tetracycline, moderate to kanamycin and low to amoxicillin/clavulanic acid and cefazolin. The MIC50/90 of danofloxacin, enrofloxacin and marbofloxacin were 0.03 and 0.06 μg/mL. For Klebsiella spp. (n = 70), similar results were noted, except for ampicillin and kanamycin. We detected 3.7 % (11/295) Enterobacteriaceae isolates carrying an ESBL/AmpC gene. Staphylococcus aureus (n = 247) and coagulase-negative staphylococci (CoNS; n = 189) isolates were susceptible to most antimicrobials tested except to penicillin (25.1 and 29.1 % resistance). Two S. aureus and thirteen CoNS isolates harboured mecA gene. Streptococcus uberis isolates (n = 208) were susceptible to β-lactam antibiotics (87.1-94.7 % susceptibility), 23.9 % were resistant to erythromycin and 37.5 % to tetracycline. Resistance to pirlimycin was moderate. For Streptococcus dysgalactiae (n = 132) the latter figures were 10.6 and 43.2 %; pirlimycin resistance was low. MIC values for Streptococcus agalactiae, Trueperella pyogenes and Corynebacterium spp. were generally low. This current VetPath study shows that mastitis pathogens were susceptible to most antimicrobials with exceptions of staphylococci against penicillin and streptococci against erythromycin or tetracycline. For most antimicrobials, the percentage resistance and MIC50/90 values among the major pathogens were comparable to that of the preceeding VetPath surveys. This work highlights the high need to set additional clinical breakpoints for antimicrobials frequently used to treat mastitis

New antimicrobial susceptibility data from monitoring of Mycoplasma bovis isolated in Europe

Mycoplasma bovis is an important respiratory pathogen of cattle across Europe and is included in the MycoPath pan-European antimicrobial susceptibility monitoring programme. M. bovis strains (232) were isolated from cattle, not recently treated with antimicrobials, at diverse geographical locations in France, Great Britain, Hungary, Italy and Spain during 2014 to 2016. Only one isolate per farm and per outbreak was retained. For each isolate, the MICs of ten antimicrobials were determined in a central laboratory using a broth microdilution method with modified Eaton’s medium and incubation at 35 °C ± 1 °C for 24 ± 6 h. MIC50/MIC90 (mg/L) values for the 232 strains were: danofloxacin 0.25/1; enrofloxacin 0.5/8; marbofloxacin 1/4; gamithromycin > 64/ > 64; spiramycin 8/16; tilmicosin > 64/ > 64; tulathromycin > 64/ > 64; tylosin 64/ > 64; florfenicol 4/8; oxytetracycline 8/32. Minor between-country differences in the MIC90 values were observed for the fluoroquinolones, spiramycin and oxytetracycline, whilst the MIC values for the other compounds were similar. Spain and Italy had the higher MIC90 values for the fluoroquinolones. Compared with the 2010–2012 study (156 isolates) results are similar, with an overall MIC50 increase of at most one doubling dilution for enrofloxacin, spiramycin, tylosin, florfenicol and oxytetracycline. In contrast, the MIC90 value for oxytetracycline decreased from > 64 to 32 mg/L. Standardized laboratory methods and interpretive criteria for MIC testing of veterinary mycoplasmas are clearly needed; there are currently no clinical breakpoints available to facilitate data interpretation and correlation of MICs with in vivo efficacy