Formulation and Immunogencity studies of Type III Secretion System needle antigens as Vaccine Candidates

Bacterial infections caused by Shigella flexneri, Salmonella typhimurium and Burkholderia pseudomallei are currently difficult to prevent due to the lack of a licensed vaccine. Here we present formulation and immunogenicity studies for the three type III secretion system (TTSS) needle proteins MxiHΔ5, PrgIΔ5 and BsaLΔ5 (each truncated by five residues at its C terminus) as potential candidates for vaccine development. These antigens are found to be thermally stabilized by the presence of carbohydrates and polyols. Additionally, all adsorb readily to aluminum hydroxide apparently through a combination of hydrogen bonds and/or Van der Waals forces. The interaction of these proteins with the aluminum-based adjuvant changes with time to resulting in varying degrees of irreversible binding. Peptide maps of desorbed protein, however, suggest that chemical changes are not responsible for this irreversible association. The ability of MxiHΔ5 and PrgIΔ5 to elicit strong humoral immune responses was tested in a murine model. When administered intramuscularly as monomers, the needle components exhibited dose dependent immunogenic behavior. The polymerized version of MxiH was exceptionally immunogenic even at low doses. The responses of both monomeric and polymerized forms were boosted by adsorption to an aluminum salt adjuvant

Cervicovaginal bacterial communities in reproductive-aged Tanzanian women with Schistosoma mansoni, Schistosoma haematobium, or without schistosome infection

Schistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV acquisition and have not been studied in schistosome infection. We collected cervical swabs from Tanzanian women with and without S. mansoni and S. haematobium to determine effects on cervicovaginal microbiota. Infected women were treated, and follow-up swabs were collected after 3 months. 16S rRNA sequencing was performed on DNA extracted from swabs. We compared 39 women with S. mansoni with 52 uninfected controls, and 16 with S. haematobium with 27 controls. S. mansoni-infected women had increased abundance of Peptostreptococcus (p = 0.026) and presence of Prevotella timonesis (p = 0.048) compared to controls. High-intensity S. haematobium infection was associated with more diverse cervicovaginal bacterial communities than uninfected controls (p = 0.0159). High-intensity S. mansoni infection showed a similar trend (p = 0.154). At follow-up, we observed increased alpha diversity in S. mansoni (2.53 vs. 1.72, p = 0.022) and S. haematobium (2.05 vs. 1.12, p = 0.066) infection groups compared to controls. Modifications in cervicovaginal microbiota, particularly increased diversity and abundance of taxa associated with bacterial vaginosis and HIV (Peptostreptococcus, Prevotella), were associated with schistosome infection.Host-parasite interactio

Identification of "Salmonella" high risk pig-herds in Belgium by using semiparametric quantile regression

Consumption of pork that is contaminated with "Salmonella" is an important source of human salmonellosis world wide. To control and prevent salmonellosis, Belgian pig-herds with high "Salmonella" infection burden are encouraged to take part in a control programme supporting the implementation of control measures. The Belgian government decided that only the 10% of pig-herds with the highest "Salmonella" infection burden (denoted high risk herds) can participate. To identify these herds, serological data reported as sample-to-positive ratios (SP-ratios) are collected. However, SP-ratios have an extremely skewed distribution and are heavily subject to confounding seasonal and animal age effects. Therefore, we propose to identify the 10% high risk herds by using semiparametric quantile regression with "P"-splines. In particular, quantile curves of animal SP-ratios are estimated as a function of sampling time and animal age. Then, pigs are classified into low and high risk animals with high risk animals having an SP-ratio that is larger than the corresponding estimated upper quantile. Finally, for each herd, the number of high risk animals is calculated as well as the beta-binomial "p"-value reflecting the hypothesis that the "Salmonella" infection burden is higher in that herd compared with the other herds. The 10% pig-herds with the lowest "p"-values are then identified as high risk herds. In addition, since high risk herds are supported to implement control measures, a risk factor analysis is conducted by using binomial generalized linear mixed models to investigate factors that are associated with decreased or increased "Salmonella" infection burden. Finally, since the choice of a specific upper quantile is to a certain extent arbitrary, a sensitivity analysis is conducted comparing different choices of upper quantiles. Copyright (c) 2008 Royal Statistical Society.

Efficiency of a Lactobacillus plantarum-xylanase combination on growth performances, microflora populations, and nutrient digestibilities of broilers infected with Salmonella Typhimurium

Three experiments were performed to assess the ability of a Lactobacillus plantarum probiotic combined with a xylanase to reduce the effects of S. typhimurium infection in broiler chickens from 1- to 30- or 42-d-old. Chicks were challenged at 3-d-old with 108 or 105 cfu S. typhimurium/chick. Four diets were studied: a wheat-based diet (C+) supplemented with 0.1 g/kg xylanase (E), or 106 cfu/g or L. plantarum (P), or both (PE). Uninfected chicks fed the C diet were used as negative control (C-). Six or 8 chicks were housed per cage with 9 cages/treatment. Growth performance and feed conversion ratio (FCR) were recorded weekly. In experiment 1, bacterial enumeration in caeca was achieved using the fluorescent in situ hybridization technique. Salmonella enumeration was realized in excreta by microbiological cultures (Exp. 2 and 3). Nutrient digestibilities and AMEn were determined in experiment 3 from d 35 to d 39. Infection with S. typhimurium led to a significant decrease in the daily weight gain (DWG) by 23.6% to 32.8%, whereas FCR was increased by 1.0% to 19.7%. Chickens fed the PE diet showed significantly improved performance in comparison with C+ birds (DWG: +12.5% in Exp. 1; FCR: -2.1-8.6%), and in comparison with the P and E treatments (DWG: +6.3-8.3% in Exp. 1; FCR: -2.7-6.4%). In experiment 3, the FCR was significantly improved by 3% with the PE diet in comparison with C- chickens. The PE combination tended to restore a microflora similar to that of uninfected broilers, whereas the P and E diets had less of an effect on the profile of bacterial communities. At slaughter age, Salmonella contamination was reduced by 2.00 and 1.85 log cfu for the E and PE treatment, respectively. The PE diet significantly reduced the crude fat digestibility by 9.2%, in comparison with the C+ chickens. These results suggest that combination between L. plantarum and a xylanase as feed additive could be effective for reduction of detrimental effect following S. typhimurium infection of broilers.Recherche d'un probiotique travaillant en synergie avec une hémicellulase en alimentation aviair