Dataset Information

Protective Effect of Oral BCG and Inactivated Mycobacterium bovis Vaccines in European Badgers (Meles meles) Experimentally Infected With M. bovis.

ABSTRACT: In Europe, badgers (Meles meles) are recognized as major tuberculosis (TB) reservoir hosts with the potential to transmit infection to associated cattle herds. Recent studies in Spain have demonstrated that vaccination with a heat-inactivated Mycobacterium bovis vaccine (HIMB) successfully protects captive wild boar and red deer against progressive disease. The aim of this study was to evaluate the efficacy of two oral vaccines against TB in a badger model: the live-attenuated M. bovis bacillus Calmette-Guérin BCG vaccine (Danish strain) and a HIMB vaccine. Twenty-four badgers were separated in three treatment groups: oral vaccinated with live BCG (108 CFU, n = 5), oral vaccinated with HIMB (107 CFU, n = 7), and unvaccinated controls (n = 12). All badgers were experimentally infected with M. bovis (103 CFU) by the endobronchial route targeting the right middle lung lobe. Throughout the study, clinical, immunological, pathological, and bacteriological parameters of infection were measured. Both vaccines conferred protection against experimental TB in badger, as measured by a reduction of the severity and lesion volumes. Based on these data, HIMB vaccination appears to be a promising TB oral vaccine candidate for badgers in endemic countries.

SUBMITTER: Balseiro A

PROVIDER: S-EPMC7011093 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Protective Effect of Oral BCG and Inactivated Mycobacterium bovis Vaccines in European Badgers (Meles meles) Experimentally Infected With M. bovis.

Balseiro Ana A Prieto José Miguel JM Álvarez Vega V Lesellier Sandrine S Davé Dipesh D Salguero Francisco J FJ Sevilla Iker A IA Infantes-Lorenzo José Antonio JA Garrido Joseba M JM Adriaensen Hans H Juste Ramón A RA Barral Marta M

Frontiers in veterinary science 20200204

In Europe, badgers (Meles meles) are recognized as major tuberculosis (TB) reservoir hosts with the potential to transmit infection to associated cattle herds. Recent studies in Spain have demonstrated that vaccination with a heat-inactivated Mycobacterium bovis vaccine (HIMB) successfully protects captive wild boar and red deer against progressive disease. The aim of this study was to evaluate the efficacy of two oral vaccines against TB in a badger model: the live-attenuated M ...[more]

PMID: 32118064

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Project description:Tuberculosis (TB) vaccination could be used as a key part of integrated strategies for the disease's control if an effective and safe vaccine under field conditions is obtained. Recent studies in Spain have evaluated the protective efficacy of two oral vaccines against experimental challenge with live intra-bronchial Mycobacterium bovis in captive badgers: the live-attenuated M. bovis BCG vaccine (Danish strain) and a heat-inactivated M. bovis (HIMB) vaccine. With the objective of increasing the knowledge of the cellular development progress of infection and generating further tools to discriminate between mild and severe TB lesions between and within animals, the immunopathology of tuberculous lesions was studied to characterize the local immune response (cell type profile) within lung granulomas from control (non-vaccinated), BCG vaccinated and HIMB-vaccinated experimentally infected badgers with M. bovis. Four immunohistochemical protocols, for the specific detection of macrophages, T lymphocytes, B lymphocytes and plasma cells within TB granulomas in formalin fixed sections of the right middle lung lobe (lobe targeted for the M. bovis delivery), were performed. Immunolabelled sections were scanned and five randomly selected areas were analyzed with digital image analysis software. The results were expressed as the proportion of the positively immunolabelled area within the total area of the selected site. Data was analyzed using the statistical analysis software (SAS). In the three treatment groups, macrophages were the most abundant inflammatory cells within the granulomas, followed by B lymphocytes and plasma cells. T lymphocyes were absent in those granulomas. This would suggest a predominance of a non-specific innate response mediated by phagocytic cells over an adaptative humoral immune response. The proportion of macrophages and plasma cells was higher in BCG and HIMB-vaccinated badgers, respectively, suggesting the establishment of an adaptative humoral response in HIMB-vaccinated badgers. The lower bacterial load at the lung level, as well as the volume of lesions in lungs using magnetic resonance imaging in badgers with the HIMB vaccine in relation with local immune response presented, must be highlighted, since it would be an advantage in favor of its use under field conditions in terms of reducing TB transmission and environmental contamination.

Project description:BackgroundBovine tuberculosis (bTB) caused by Mycobacterium bovis is the most serious endemic disease affecting livestock in the UK. The European badger (Meles meles) is the most important wildlife reservoir of bTB transmission to cattle, making eradication particularly difficult. In this respect, oral vaccination with the attenuated M. bovis vaccine Bacillus Calmette-Guerin (BCG) has been suggested as a wide-scale intervention to reduce bTB infection in badgers. However, experimental studies show variable protection. Among the possibilities for this variation is that the resident gut bacteria may influence the success of oral vaccination in badgers; either through competitive exclusion and/or inhibition, or via effects on the host immune system. In order to explore this possibility, we have tested whether typical gut commensals such as Lactic Acid Bacteria (LAB) have the capacity to impact on the viability and survival rate of BCG and to modulate the immune response to BCG using an in vitro model.ResultsTwelve LAB isolated from badger faeces displayed inhibitory activity to BCG that was species-dependent. Weissella had a bacteriostatic effect, whereas isolates of enterococci, lactobacilli and pediococci had a more bactericidal activity. Furthermore, BCG-induced activation of the pro-inflammatory transcription factor NF-κB in human THP-1 macrophages was modulated by LAB in a strain-dependent manner. Most pediococci enhanced NF-κB activation but one strain had the opposite effect. Interestingly, isolates of enterococci, lactobacilli and weissella had different effects as immunomodulators of BCG-induced macrophage responses as some had no significant influence on NF-κB activation, but others increased it significantly.ConclusionsOur in vitro results show that LAB isolated from badgers exhibit significant inhibitory activity against BCG and influence the immune activation mediated by BCG in a human macrophage assay. These findings suggest that gut commensal bacteria could play a role in influencing the outcome of oral BCG vaccination. Inactivated cells of LAB, or LAB that are bacteriostatic but have a synergistic immunostimulatory effect with BCG, could be potential adjuvants to be used for oral vaccination in badgers. Further work is needed to take into account the complex nature of the gut microbiome, specific immunity of the badger and the in vivo context.

Dataset Information

Protective Effect of Oral BCG and Inactivated Mycobacterium bovis Vaccines in European Badgers (Meles meles) Experimentally Infected With M. bovis.

Publications

Protective Effect of Oral BCG and Inactivated <i>Mycobacterium bovis</i> Vaccines in European Badgers (<i>Meles meles</i>) Experimentally Infected With <i>M. bovis</i>.

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