The response of red deer to oral administration of heat-inactivated Mycobacterium bovis and challenge with a field strain

Thomas, Jobin; Risalde, María Ángeles; Serrano, Miriam; Sevilla, Iker A.; Geijó, Mariví; Ortíz, José Antonio; Fuertes, M.; Ruíz-Fons, José Francisco; Fuente, José de la; Domı́nguez, Lucas; Juste, Ramón A.; Garrido, Joseba M.; Gortázar, Christian

doi:10.1016/j.vetmic.2017.08.007

Cited by 33 publications

(38 citation statements)

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“…This state of “anergy” is recorded in animals subjected to stress and in cattle with advanced or generalized TB [ 10 , 65 ]. This agrees with the findings observed in our study, in which the deer inoculated intratracheally with 10 6 CFU of M. bovis had generalized TB with a massive growth of mycobacteria in different tissues [ 43 ], which could explain this state of immunosuppression at 60 dpi. However, the suppression of the CMI appears to drift to a humoral immune response according to the response of antibodies to bPPD observed at necropsy time.…”

Section: Discussionsupporting

confidence: 93%

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Development and evaluation of an interferon gamma assay for the diagnosis of tuberculosis in red deer experimentally infected with Mycobacterium bovis

et al. 2017

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BackgroundRed deer (Cervus elaphus) is regarded as an epidemiologically relevant host for Mycobacterium bovis (M. bovis) and closely related members of the Mycobacterium tuberculosis complex that cause animal tuberculosis (TB). The standard antemortem screening test for the detection of TB in deer is the intradermal tuberculin skin test, but the detection of interferon-gamma (IFNγ) produced by white blood cells exposed to M. bovis antigens can be used as an alternative or supplemental assay in most TB eradication/control programs. This study aims to develop an in-house sandwich ELISA for deer IFNγ, based on the cross-reactivity of the antibodies to both cervid and bovine IFNγ, and to evaluate the potential of this assay to detect M. bovis-infected red deer in response to the in vitro stimulation of whole-blood cells with bovine purified protein derivative (bPPD), p22 protein complex derived from bPPD or using the specific tuberculous mycobacterial proteins ESAT-6/CFP-10, Rv3615c and Rv3020c. The positive control stimulant used in this study was pokeweed mitogen, which resulted in a consistent induction of IFNγ in samples from red deer, thus allowing the interpretation of the assay.ResultsThe percentage of animals correctly classified by this technique as M. bovis non-infected was 100%. The detection of infected animals as positive was high and ranged widely depending upon the antigen and the cut-off value applied, as well as the time after infection. Our findings indicate that this protocol may serve as a reliable assay for the antemortem diagnosis of TB from the initial stage of M. bovis-infection, and may also be adequately sensitive.ConclusionsThe suggested optimal antigens and cut-off are bPPD, p22 and the combination of ESAT-6/CFP-10 and Rv3020c with a 0.05 Δ optical density, which yielded a up to 100% correct classification of TB positive and negatve red deer under our experimental conditions. This technique will aid in TB testing of farmed and translocated deer. Future studies should evaluate the ability of this IFNγ assay to detect specific responses under field conditions.Electronic supplementary materialThe online version of this article (10.1186/s12917-017-1262-6) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 93%

“…An experimental infection with M. bovis was carried out as part of a vaccine trial [ 43 ]. For the challenge, a M. bovis field strain (2008/2575) was propagated in Middlebrook 7H9 broth containing 10% OADC Enrichment (Becton, Dickinson and Company, New Jersey, USA), 0.2% glycerol and 0.05% Tween 80 ( v /v).…”

Section: Methodsmentioning

confidence: 99%

Development and evaluation of an interferon gamma assay for the diagnosis of tuberculosis in red deer experimentally infected with Mycobacterium bovis

et al. 2017

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“…Application of an orally-administered, heat-inactivated M. bovis vaccine to bovine tuberculosis-affected wild boar populations in Spain appears to have helped in reducing disease prevalence [8]. In addition, that vaccine preparation administered orally has shown some efficacy in protecting cattle and cervids, as well as goats and wild boar parenterally [9][10][11][12][13]. Here, we describe the use of heat-inactivated M. bovis vaccine in wild pigs of Molokai origin, and its efficacy against experimental infection with virulent M. bovis.…”

Section: Introductionmentioning

confidence: 99%

“…Average lesion score based on examination of 23 tissues; 2 Bilateral tissues were collected and total score from both tissues reported here;3 Caud, Caudal Lung Lobes;4 Cran, Cranial Lung Lobes;5 Card, Cardiac Lung Lobes;6 Acc, Accessory Lung Lobe;7 Mand, Mandibular Lymph Nodes;8 Superf Cerv, Superficial Cervical Lymph Nodes;9 Medias, Mediastinal Lymph Node;10 Tracheo-bronch, Tracheobronchial Lymph Nodes;11 Hep, Hepatic Lymph Node;12 Mes, Mesenteric Lymph Node;13 Shaded cells have at least one positive outcome.…”

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Effects of Inactivated Mycobacterium bovis Vaccination on Molokai-Origin Wild Pigs Experimentally Infected with Virulent M. bovis

et al. 2020

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The wild pig population on Molokai, Hawaii, USA is a possible reservoir for bovine tuberculosis, caused by Mycobacterium bovis, and has been implicated in decades past as the source of disease for the island's domestic cattle. Heat-inactivated vaccines have been effective for reducing disease prevalence in wild boar in Spain and could prove useful for managing M. bovis in Molokai wild pigs. We designed an experiment to test this vaccine in wild pigs of Molokai genetics. Fifteen 3-4-month-old pigs were orally administered 10 6 -10 7 colony forming units (cfu) of heat-inactivated M. bovis (Vaccinates; n = 8; 0.2 mL) or phosphate buffered saline (Controls; n = 7; 0.2 mL). Each dose was administered in a 0.5 mL tube embedded in a fruit candy/cracked corn mix. Boosters were given seven weeks post-prime in the same manner and dose. Nineteen weeks post-prime, pigs were orally challenged with 1 × 10 6 cfu of virulent M. bovis. Twelve weeks post-challenge, pigs were euthanized and necropsied, at which time 23 different tissues from the head, thorax, and abdomen were collected and examined. Each tissue was assigned a lesion score. Ordinal lesion score data were analyzed using non-parametric Wilcoxon Signed Rank test. Effect size was calculated using Cohen's d. Four of eight Vaccinates and four of seven Controls had gross and microscopic lesions, as well as culture-positive tissues. Vaccinates had statistically lower lesion scores than Controls in the following areas: gross thoracic lesion scores (p = 0.013 Cohen's d = 0.33) and microscopic thoracic lesion scores (p = 0.002, Cohen's d = 0.39). There were no differences in head lesion scores alone, both gross and microscopic, nor were there differences when comparing combined gross and microscopic head and thoracic lesion

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“…Heat-inactivated M. bovis (oral and parenteral) has been shown to reduce disease severity in wild boar ( 82 , 116 ) similar to protection provided through vaccination with BCG ( 117 ), without risk of environmental contamination or spread to non-target species. Similarly, heat-inactivated M. bovis has been shown to decrease disease severity in experimentally infected red deer ( 118 ). Another noted advantage to heat-inactivated M. bovis is that vaccinated calves did not have false positive responses in either antibody-based assays or interferon gamma release assays measuring cell-mediated immune responses ( 118 ) reducing concern that vaccine exposed cattle would be falsely identified as M. bovis infected during routine surveillance.…”

Section: Future Directionsmentioning

confidence: 99%

Use of the Human Vaccine, Mycobacterium bovis Bacillus Calmette Guérin in Deer

Palmer

Thacker

2018

Front. Vet. Sci.

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The only vaccine ever approved for human tuberculosis was developed a century ago from an isolate of Mycobacterium bovis derived from a tuberculous cow. Initial safety and efficacy studies of an attenuated version of this isolate were conducted in cattle and other animals. In 1921 the first human, an infant, was orally dosed with this attenuated strain that came to be known as M. bovis bacillus Calmette-Guérin (BCG); named for Albert Calmette and Camille Guérin, the two French scientists that developed the strain. Since 1921, billions of people have been vaccinated with BCG making it the oldest, most widely used, and safest vaccine in use today. It is also the tuberculosis vaccine most studied for use in wildlife, including deer. While BCG vaccination of deer may not reliably prevent infection, it consistently decreases lesion severity, minimizing large, necrotic lesions, which often contain large numbers of bacilli. It is believed that decreased lesion severity correlates with decreased disease transmission; however, this hypothesis remains to be proven. Safety studies in white-tailed deer show BCG may persist in lymphoid tissues for up to 12 months; a factor to be considered in deer used for food. Beyond efficacy and safety, methods of vaccine delivery to free-ranging deer are also under investigation, both in the laboratory and in the field. The ideal delivery method is effective, efficient and safe for non-target species, including livestock. Ingestion of BCG by cattle is of special concern as such cattle may present as “false positives” using currently approved diagnostic methods, thus interfering with efforts by animal health agencies to monitor cattle for tuberculosis. An effective BCG vaccine for deer would be of value in regions where free-ranging deer represent a potential source of M. bovis for livestock. Such a vaccine would also be beneficial to farmed deer where M. bovis represents a serious threat to trade and productivity.

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The response of red deer to oral administration of heat-inactivated Mycobacterium bovis and challenge with a field strain

Cited by 33 publications

References 31 publications

Development and evaluation of an interferon gamma assay for the diagnosis of tuberculosis in red deer experimentally infected with Mycobacterium bovis

Development and evaluation of an interferon gamma assay for the diagnosis of tuberculosis in red deer experimentally infected with Mycobacterium bovis

Effects of Inactivated Mycobacterium bovis Vaccination on Molokai-Origin Wild Pigs Experimentally Infected with Virulent M. bovis

Use of the Human Vaccine, Mycobacterium bovis Bacillus Calmette Guérin in Deer

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