A long-term study in Angora goats experimentally infected with Mycobacterium avium subsp. paratuberculosis: Clinical disease, faecal culture and immunological studies

Stewart, David J.; Vaughan, J.A.; Stiles, Paula L; Noske, P; Tizard, Mark; Prowse, Stephen J.; Michalski, Wojtek P.; Butler, K. L.; Jones, Stephen L.

doi:10.1016/j.vetmic.2005.09.015

Cited by 53 publications

(35 citation statements)

References 17 publications

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“…Although PBMCs of Sal-Ag induced significantly lower level of IFN-γ than MAP316F, the level was significantly higher than PBS and vector controls at week 6, 10 and 14 which correlated well with partial protection as increased expression of this cytokine is observed during early stage of infection and reduction in its level is the hallmark of clinical JD [37], [38]. The low level of antibodies induced after vaccination, which declined sharply after challenge, agrees well with previous reports where strong humoral responses occur at a later time point after infection and suggests that antibodies are usually not protective but is indicative of breakdown of CMI leading to rapid progression of disease [39], [40], [40,41]. Significant differences in proliferation and activation of T cells (CD4 and CD8) were observed between Sal-Ag and MAP316F correlating to protection, which is in accordance with previous studies that showed that cows infected with MAP have increased levels of these cells [40], [42].…”

Section: Discussionsupporting

confidence: 88%

“…al . but also provide detailed insight to early immune responses (antibody, IFN-γ, cytokines, T cells) to MAP vaccination and infection [39], [41]. Most importantly, our data indicate that Sal-Ag provided partial protection as it was able to limit MAP colonization to some extent and the tissue burden was low to moderate but did not achieve a statistically significant level that was seen with MAP316F.…”

Section: Discussionmentioning

confidence: 76%

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Evaluation of a Salmonella Vectored Vaccine Expressing Mycobacterium avium Subsp. paratuberculosis Antigens Against Challenge in a Goat Model

et al. 2013

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Johnes disease (JD), caused by Mycobacterium avium subsp paratuberculosis (MAP), occurs worldwide as chronic granulomatous enteritis of domestic and wild ruminants. To develop a cost effective vaccine, in a previous study we constructed an attenuated Salmonella strain that expressed a fusion product made up of partial fragments of MAP antigens (Ag85A, Ag85B and SOD) that imparted protection against challenge in a mouse model. In the current study we evaluated the differential immune response and protective efficacy of the Sal-Ag vaccine against challenge in a goat model as compared to the live attenuated vaccine MAP316F. PBMCs from goats vaccinated with Sal-Ag and challenged with MAP generated significantly lower levels of IFN-γ, following in vitro stimulation with either Antigen-mix or PPD jhonin, than PBMC from MAP316F vaccinated animals. Flow cytometric analysis showed the increase in IFN-γ correlated with a significantly higher level of proliferation of CD4, CD8 and γδT cells and an increased expression of CD25 and CD45R0 in MAP316F vaccinated animals as compared to control animals. Evaluation of a range of cytokines involved in Th1, Th2, Treg, and Th17 immune responses by quantitative PCR showed low levels of expression of Th1 (IFN-γ, IL-2, IL-12) and proinflammatory cytokines (IL-6, IL-8, IL-18, TNF-α) in the Sal-Ag immunized group. Significant levels of Th2 and anti-inflammatory cytokines transcripts (IL-4, IL-10, IL-13, TGF-β) were expressed but their level was low and with a pattern similar to the control group. Over all, Sal-Ag vaccine imparted partial protection that limited colonization in tissues of some animals upon challenge with wild type MAP but not to the level achieved with MAP316F. In conclusion, the data indicates that Sal-Ag vaccine induced only a low level of protective immunity that failed to limit the colonization of MAP in infected animals. Hence the Sal-Ag vaccine needs further refinement to increase its efficacy.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 76%

Evaluation of a Salmonella Vectored Vaccine Expressing Mycobacterium avium Subsp. paratuberculosis Antigens Against Challenge in a Goat Model

et al. 2013

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“…Higher levels of antigen-specific IFN-␥ secreted by peripheral blood mononuclear cells (PBMCs) have been reported for animals in the early stages of M. avium subsp. paratuberculosis infection, whether it be natural or experimental infection (11,18,22,24). Since IFN-␥ is a key effector cytokine involved in the activation of T cells and macrophages, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC) class I and II molecules, and production of reactive oxygen and nitrogen species by macrophages, it is purported to be not only an immune response variable but also a correlate of immune protection (7,16).…”

mentioning

confidence: 99%

Early Immune Markers Associated withMycobacterium aviumsubsp.paratuberculosisInfection in a Neonatal Calf Model

Stabel

Robbe‐Austerman

2011

Clin Vaccine Immunol

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The objective of this study was to observe early markers of cell-mediated immunity in naïve calves infected with Mycobacterium avium subsp. paratuberculosis and how expression of these markers evolved over the 12-month period of infection. Groups for experimental infection included control (noninfected), oral (infected orally with M. avium subsp. paratuberculosis strain K-10), oral/DXM (pretreatment with dexamethasone before oral inoculation), intraperitoneal (i.p.) inoculation, and oral/M (oral inoculation with mucosal scrapings from a cow with clinical disease) groups. One of the earliest markers to emerge was antigen-specific gamma interferon (IFN-␥). Only i.p. inoculated calves had detectable antigen-specific IFN-␥ responses at 7 days, with responses of the other infection groups becoming detectable at 90 and 120 days. All infection groups maintained robust IFN-␥ responses for the remainder of the study. At 1 month, calves in the oral and oral/M groups had higher antigen-stimulated interleukin-10 (IL-10) levels than calves in the other treatment groups, but IL-10 secretion declined by 12 months for all calves. T-cell activation markers such as CD25, CD26, CD45RO, and CD5 were significantly upregulated in infected calves compared to noninfected controls. Oral inoculation of calves resulted in significantly increased antigen-specific lymphocyte proliferation at 9 and 12 months, as well as inducible nitric oxide synthase (iNOS) secretion at 6 and 12 months. These results demonstrate that infection of naïve calves with M. avium subsp. paratuberculosis invoked early immunologic responses characterized by robust antigen-specific IFN-␥ responses and induction of CD25 and CD45RO expression on T-cell subsets. These were followed by antigen-specific lymphocyte proliferation, iNOS secretion, and expression of CD26 and CD5 bright markers in the latter part of the 12-month study.Deciphering host immune responses upon exposure to Mycobacterium avium subsp. paratuberculosis, differentiating the responses due to exposure from true infection, and then further characterizing responses at different stages of infection have been daunting and complex tasks that remain elusive. Early measures of host immune responses to infection with mycobacteria, including M. avium subsp. paratuberculosis, have been dominated by a strong bias toward Th1-mediated gamma interferon (IFN-␥) production. Higher levels of antigen-specific IFN-␥ secreted by peripheral blood mononuclear cells (PBMCs) have been reported for animals in the early stages of M. avium subsp. paratuberculosis infection, whether it be natural or experimental infection (11,18,22,24). Since IFN-␥ is a key effector cytokine involved in the activation of T cells and macrophages, maturation of dendritic cells, upregulation of major histocompatibility complex (MHC) class I and II molecules, and production of reactive oxygen and nitrogen species by macrophages, it is purported to be not only an immune response variable but also a correlate of immune protection (7,16). However, it is u...

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“…Therefore, the sensitivity of the ELISA is limited in unvaccinated goats. Yet goats are seemingly the least naturally resistant to MAP, resulting in persistent fecal shedding, seroconversion, and clinical disease following MAP challenge [35]. Compared to other species this potentially attributes to an increased sensitivity of the ELISA and even so PCR.…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium avium Subspecies paratuberculosis DNA and Antibodies in Dairy Goat Colostrum and Milk

Lievaart‐Peterson

Luttikholt

Gonggrijp

et al. 2019

Veterinary Sciences

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Mycobacterium avium subspecies paratuberculosis (MAP) is endemic in the Dutch dairy goat population causing economic loss, and negatively influencing welfare. Moreover, there are concerns about a potential zoonotic risk. Therefore the industry's objectives are to decrease MAP prevalence, limit economic losses as well as reduce the concentration of MAP in (bulk) milk. To diminish within-farm spread of infection, vaccination, age dependent group housing with separation of newborns from adults, as well as rearing on artificial or treated colostrum and milk replacers are implemented. However, the importance of MAP contaminated colostrum and milk as a route of infection in dairy goat herds is unknown. Therefore the aim of this study was to detect the presence of MAP DNA in colostrum and milk from dairy goats in infected herds. A convenience sample of 120 colostrum samples and 202 milk samples from MAP infected dairy goat herds were tested by IS900 real-time Polymerase Chain Reaction (PCR) for MAP DNA. Furthermore, 22 colostrum samples and 27 post mortem milk samples of goats with clinical signs consistent with paratuberculosis from known infected herds were tested. The majority of samples were from goats vaccinated against MAP. Positive or doubtful PCR results were obtained in none of the 120 and two of the 22 colostrum samples, and in eight of the 202 and four of the 27 milk samples Negative PCR results were obtained in the remaining 140 (99%) colostrum samples and 217 (95%) milk samples.

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A long-term study in Angora goats experimentally infected with Mycobacterium avium subsp. paratuberculosis: Clinical disease, faecal culture and immunological studies

Cited by 53 publications

References 17 publications

Evaluation of a Salmonella Vectored Vaccine Expressing Mycobacterium avium Subsp. paratuberculosis Antigens Against Challenge in a Goat Model

Evaluation of a Salmonella Vectored Vaccine Expressing Mycobacterium avium Subsp. paratuberculosis Antigens Against Challenge in a Goat Model

Early Immune Markers Associated withMycobacterium aviumsubsp.paratuberculosisInfection in a Neonatal Calf Model

Mycobacterium avium Subspecies paratuberculosis DNA and Antibodies in Dairy Goat Colostrum and Milk

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