scholarly journals Protective Efficacy of Chitosan Coupled Johne’s Disease Vaccine

Author(s):  
B. Vasanthi ◽  
S. Pavithra ◽  
K. Vijayarani ◽  
R. Venkataramanan ◽  
K. Kumanan

Background: Johne’s disease (JD) is a chronic, economically important disease of domestic ruminants. Continuous efforts are being made to develop a potent vaccine for JD which confer a longer immunity. The present study was aimed at developing chitosan nanoparticles coupled JD vaccine and assess its efficacy. Methods: Potency of a heat killed, chitosan nanoparticle coupled JD vaccine developed with an Indian isolate of Mycobacterium avium subsp paratuberculosis (MAP) was tested in 107 goats. Pre and post immunization blood samples were collected at different time points and peripheral blood mononuclear cells were used for assessing IFN-γ, IL-2, IL-10 and IL-12 gene expressions. Immunized animals were challenged with a field isolate of MAP and the immune response was assessed. Result: Immunized goats were safe with no untoward reactions. Cytokine gene expression studies indicated a good Th1 response during 3-14 wk post immunization. The initial Th1 response was followed by a good Th2 response with a better IL-10 response than the IFN-γ and IL-2 responses in vaccinated animals at 23 wk PI. Both Th1 and Th2 responses were significantly higher in immunized animals at 23 and 34 weeks post challenge indicating a protective immune response.

2011 ◽  
Vol 18 (9) ◽  
pp. 1467-1476 ◽  
Author(s):  
Dairu Shu ◽  
Supatsak Subharat ◽  
D. Neil Wedlock ◽  
Dongwen Luo ◽  
Geoffrey W. de Lisle ◽  
...  

ABSTRACTMycobacterium aviumsubsp.paratuberculosis, the causative agent of Johne's disease, is able to dampen or distort immune responses at the mucosal sites and coexist with a massive infiltration of immune cells in the gastrointestinal tract. Knowledge of the mechanism by whichM. aviumsubsp.paratuberculosissubverts the immune response at the mucosal level in cattle is important for the development of improved disease control strategies, including new vaccines and diagnostic tests. In this study, 38 cull cows from herds infected withM. aviumsubsp.paratuberculosiswere divided into four groups, based onM. aviumsubsp.paratuberculosisculture from gut tissues and histopathological lesion scores. Cytokine gene expression and secretion fromM. aviumsubsp.paratuberculosissonicate-stimulated peripheral blood mononuclear cell (PBMC) and mesenteric lymph node (MLN) cultures of the animals were compared. Antigen stimulation of MLN cells from the severely lesioned group resulted in significant upregulation of the mRNA expression of five cytokines, gamma interferon (IFN-γ), interleukin-10 (IL-10), IL-13, IL-17A, and tumor necrosis factor alpha (TNF-α), which have a diverse range of functions, while there was no significant upregulation of these cytokines by the other groups. There were major differences between the responses of the PBMC and MLN cultures, with higher levels of secreted IFN-γ released from the MLN cultures and, conversely, higher levels of IL-10 released from the PBMC cultures. The upregulation of all five cytokines from cells at the site of infection in the severely lesioned animals suggested a dysregulated immune response, contributing to a failure to clear infection in this group of animals.


2002 ◽  
Vol 70 (11) ◽  
pp. 5938-5945 ◽  
Author(s):  
Sharon R. Chirgwin ◽  
Philip H. Elzer ◽  
Sharon U. Coleman ◽  
Jena M. Nowling ◽  
Sue D. Hagius ◽  
...  

ABSTRACT Filarial infections have been associated with the development of a strongly polarized Th2 host immune response and a severe impairment of mitogen-driven proliferation and type 1 cytokine production in mice and humans. The role of this polarization in the development of the broad spectra of clinical manifestations of lymphatic filariasis is still unknown. Recently, data gathered from humans as well as from immunocompromised mouse models suggest that filariasis elicits a complex host immune response involving both Th1 and Th2 components. However, responses of a similar nature have not been reported in immunologically intact permissive models of Brugia infection. Brucella abortus-killed S19 was inoculated into the Brugia-permissive gerbil host to induce gamma interferon (IFN-γ) production. Gerbils were then infected with B. pahangi, and the effect of the polarized Th1 responses on worm establishment and host cellular response was measured. Animals infected with both B. abortus and B. pahangi showed increased IFN-γ and interleukin-10 (IL-10) and decreased IL-4 and IL-5 mRNA levels compared with those in animals infected with B. pahangi alone. These data suggest that the prior sensitization with B. abortus may induce a down regulation of the Th2 response associated with Brugia infection. This reduced Th2 response was associated with a reduced eosinophilia and an increased neutrophilia in the peritoneal exudate cells. The changes in cytokine and cellular environment did not inhibit the establishment of B. pahangi intraperitoneally. The data presented here suggest a complex relationship between the host immune response and parasite establishment and survival that cannot be simply ascribed to the Th1/Th2 paradigm.


2013 ◽  
Vol 81 (6) ◽  
pp. 2242-2257 ◽  
Author(s):  
Pallab Ghosh ◽  
Chia-wei Wu ◽  
Adel M. Talaat

ABSTRACTMycobacterium aviumsubsp.paratuberculosiscauses Johne's disease, an enteric infection in cattle and other ruminants, greatly afflicting the dairy industry worldwide. Once inside the cell,M. aviumsubsp.paratuberculosisis known to survive harsh microenvironments, especially those inside activated macrophages. To improve our understanding ofM. aviumsubsp.paratuberculosispathogenesis, we examined phagosome maturation associated with transcriptional responses ofM. aviumsubsp.paratuberculosisduring macrophage infection. Monitoring cellular markers, only liveM. aviumsubsp.paratuberculosisbacilli were able to prevent phagosome maturation and reduce its acidification. On the transcriptional level, over 300M. aviumsubsp.paratuberculosisgenes were significantly and differentially regulated in both naive and IFN-γ-activated macrophages. These genes include the sigma factor H (sigH) that was shown to be important forM. aviumsubsp.paratuberculosissurvival inside gamma interferon (IFN-γ)-activated bovine macrophages. Interestingly, ansigH-knockout mutant showed increased sensitivity to a sustained level of thiol-specific oxidative stress. Large-scale RNA sequence analysis revealed that a large number of genes belong to thesigHregulon, especially following diamide stress. Genes involved in oxidative stress and virulence were among the induced genes in thesigHregulon with a putative consensus sequence for SigH binding that was recognized in a subset of these genes (n= 30), suggesting direct regulation by SigH. Finally, mice infections showed a significant attenuation of the ΔsigHmutant compared to its parental strain, suggesting a role forsigHinM. aviumsubsp.paratuberculosisvirulence. Such analysis could identify potential targets for further testing as vaccine candidates against Johne's disease.


2012 ◽  
Vol 80 (9) ◽  
pp. 3039-3048 ◽  
Author(s):  
Ryan J. Arsenault ◽  
Yue Li ◽  
Kelli Bell ◽  
Kimberley Doig ◽  
Andrew Potter ◽  
...  

ABSTRACTMycobacterium aviumsubsp.paratuberculosisis the causative agent of Johne's disease in cattle and may have implications for human health. Establishment of chronic infection byM. aviumsubsp.paratuberculosisdepends on its subversion of host immune responses. This includes blocking the ability of infected macrophages to be activated by gamma interferon (IFN-γ) for clearance of this intracellular pathogen. To define the mechanism by whichM. aviumsubsp.paratuberculosissubverts this critical host cell function, patterns of signal transduction to IFN-γ stimulation of uninfected andM. aviumsubsp.paratuberculosis-infected bovine monocytes were determined through bovine-specific peptide arrays for kinome analysis. Pathway analysis of the kinome data indicated activation of the JAK-STAT pathway, a hallmark of IFN-γ signaling, in uninfected monocytes. In contrast, IFN-γ stimulation ofM. aviumsubsp.paratuberculosis-infected monocytes failed to induce patterns of peptide phosphorylation consistent with JAK-STAT activation. The inability of IFN-γ to induce differential phosphorylation of peptides corresponding to early JAK-STAT intermediates in infected monocytes indicates thatM. aviumsubsp.paratuberculosisblocks responsiveness at, or near, the IFN-γ receptor. Consistent with this hypothesis, increased expression of negative regulators of the IFN-γ receptors SOCS1 and SOCS3 as well as decreased expression of IFN-γ receptor chains 1 and 2 is observed inM. aviumsubsp.paratuberculosis-infected monocytes. These patterns of expression are functionally consistent with the kinome data and offer a mechanistic explanation for this criticalM. aviumsubsp.paratuberculosisbehavior. Understanding this mechanism may contribute to the rational design of more effective vaccines and/or therapeutics for Johne's disease.


Author(s):  
Mansure HOJATIZADE ◽  
Ali BADIEE ◽  
Ali KHAMESIPOUR ◽  
Mahmoud Reza JAAFARI

Background: Whole killed Leishmania vaccine reached phase III clinical trials but failed to display significant efficacy in human mainly due to limited Th1 inducer adjuvant. Liposomes consisting of 1, 2-dioleoyl-3trimethylammonium-propane (DOTAP) bearing an inherent adjuvanticity and 1, 2-dioleoyl-L-α-glycero-3-phosphatidylethanolamine (DOPE) is well known to intensify the efficacy of positively charged liposomes. Methods: Soluble Leishmania major antigens (SLA) encapsulated in cationic liposomes using lipid film method in 2016). BALB/c mice were immunized subcutaneously (SC), three times in a 2-wk interval, with Lip (DOTAP)-SLA+, Lip (DOTAP/DOPE)-SLA+, Lip (DOTAP/DOPE/CHO)-SLA+, Lip (DOTAP/DOPE/CHO), Lip (DOPE/CHO), SLA or HEPES buffer. At week 2 after the last booster injection, immunized mice have challenged SC in the footpad with L. major parasites. To investigate the rate of protection and the type of immune response generated in mice, lesions development was assessed, IL-4 and IFN-γ levels with the ratio of IgG2a/IgG1 isotype were studied to describe the type of generated immune response. Results: Mice immunized with all liposomal form of SLA showed smaller footpad swelling and lower parasite burden in the spleen and footpad compared to the group of mice received buffer. However, these formulations did not show protection against leishmaniosis because of a generated mixed Th1/Th2 response in mice characterized by high production of IFN-γ and IL4 and a high titer of IgG1 and IgG2a antibody. Conclusion: Immunization with Lip (DOTAP/DOPE/CHO)-SLA+ was not an appropriate strategy to protect mice against leishmaniosis.


2006 ◽  
Vol 43 (2) ◽  
pp. 127-135 ◽  
Author(s):  
D. J. Weiss ◽  
O. A. Evanson ◽  
C. D. Souza

2022 ◽  
Vol 12 ◽  
Author(s):  
Yanhong Bao ◽  
Yu Yao ◽  
Zi Wang ◽  
Shuiyin Wu ◽  
Xiuyun Jiang ◽  
...  

Mycobacterium avium subsp. paratuberculosis (MAP) is the pathogen of Johne’s disease (paratuberculosis), which mainly causes chronic infectious granulomatous enteritis in ruminants and has brought huge economic losses to animal husbandry. As a specific intracellular pathogen, when MAP invades the body, it is internalized by macrophages where it is able to replicate by inhibition of the phagosome maturation, escaping the host immune system and surviving, which leads to the spread of the disease. More recent studies have shown that circRNA is involved in many pathological and physiological processes of the body as the molecular sponge of miRNA, the scaffold of RNA binding protein and having the characteristic of being able to translate into protein. In this study, the mRNA and circRNA expression profiles of MAP-infected bovine monocyte-macrophages and uninfected bovine cells were analyzed by high-throughput sequencing. A total of 618 differentially expressed mRNA were screened out, including 322 upregulated mRNA and 296 downregulated mRNA. In addition, the analysis of circRNA differential expression profile showed 39 differentially expressed genes including 12 upregulated and 27 downregulated genes. Moreover, differential genes belonging to cytokine activity, chemokine activity, inflammatory reaction, apoptosis, and other functional groups related to macrophage immune response were significantly enriched in Gene Ontology (GO). Multiple signal pathways including NF-κB, MAPK, Toll-like receptor, IL-17, JAK-STAT, and other signaling pathways related to activating macrophage immune response were significantly enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, RT-qPCR technology verified the accuracy of the mRNA sequencing results. In this study, we have obtained the transcriptome information of mRNA and circRNA of bovine monocyte-macrophage infected with MAP. These results will provide data support for the further study of mRNA–miRNA–circRNA network and immune escape mechanism of MAP and will enrich the knowledge of the molecular immune mechanisms of Johne’s disease as well.


2020 ◽  
Author(s):  
Mohammadali Alizadeh ◽  
Jegarubee Bavananthasivam ◽  
Bahram Shojadoost ◽  
Jake Astill ◽  
Khaled Abdelaziz ◽  
...  

Abstract There is some evidence that lactobacilli can strengthen immune system of chickens. This study evaluated the effects of in ovo and oral administration of a lactobacilli cocktail on cytokine gene expression, antibody-mediated immune response, and spleen cellularity in chickens. Lactobacilli were administered either in ovo at embryonic day 18, orally to hatched chicks at days 1, 7, 14, 21, and 28 post-hatches, or by both treatments combined. On days 5 and 10 post-hatch, spleen and bursa of Fabricius were collected for gene expression and cell composition analysis. On days 14 and 21 post-hatch, birds were injected with sheep red blood cells (SRBC) and keyhole limpet hemocyanin (KLH), and sera were collected on days 7, 14, and 21 post-primary immunization. Birds that received lactobacilli (107 CFU) via in ovo followed by weekly oral administration showed a greater immune response by enhancing antibody response, increasing the percentage of CD4+ and CD4+CD25+ T cells in the spleen, and upregulating the expression of the expression of interferon (IFN)-α, IFN-β, interleukin (IL)-12, and IL-13 in the spleen and expression of IFN-γ, IL-2, IL-6, IL-8, IL-12, and IL-18 in bursa. These findings suggest that pre-and post-hatch administration of lactobacilli modulate immune response in newly hatched chickens.


2008 ◽  
Vol 15 (6) ◽  
pp. 963-969 ◽  
Author(s):  
Mark Robinson ◽  
Rory O'Brien ◽  
Colin Mackintosh ◽  
Frank Griffin

ABSTRACT Immune responses of red deer (Cervus elaphus) that presented with different levels of paucibacillary pathology were profiled to detail immune changes during the progression of Johne's disease. Immune responses were monitored using an immunoglobulin G1 (IgG1) antibody enzyme-linked immunosorbent assay (ELISA), a gamma interferon (IFN-γ) ELISA, and flow cytometry. Animals in the study were divided into outcome groups postmortem according to disease severity. All animals mounted IgG1 antibody and IFN-γ responses to both the vaccination and experimental challenges. The Mycobacterium avium subsp. paratuberculosis-specific IgG1 antibody responses in the challenged group showed marked differences between infected and severely diseased animals. Slightly higher IFN-γ responses were seen in infected animals compared with severely diseased animals. No significant changes were seen in the phenotype of lymphocyte populations investigated. Vaccination with killed M. avium subsp. paratuberculosis in mineral oil adjuvant reduced the level of severe disease; however, it obscured immunological differences between the infected and severely diseased groups. This suggests protection is not exclusively mediated via the presence of a type 1 response and, furthermore, the presence of a type 2 response is compatible with protection. These profiles provide information on the different immune processes in Johne's disease progression.


2003 ◽  
Vol 71 (9) ◽  
pp. 5130-5138 ◽  
Author(s):  
W. R. Waters ◽  
J. M. Miller ◽  
M. V. Palmer ◽  
J. R. Stabel ◽  
D. E. Jones ◽  
...  

ABSTRACT Johne's disease (paratuberculosis) of cattle is widespread and causes significant economic losses for producers due to decreased production and poor health of affected animals. The chronic nature of the disease and the lack of a reproducible model of infection hinder research efforts. In the present study, instillation of Mycobacterium avium subsp. paratuberculosis into the tonsillar crypts of neonatal calves resulted in peripheral colonization as detected by antemortem culture of feces and postmortem (320 days postchallenge) culture of intestinal tissues. Antigen-specific blastogenic, gamma interferon (IFN-γ), and nitric oxide responses by blood mononuclear cells from infected calves exceeded prechallenge responses beginning 194 days postchallenge. Upon in vitro stimulation with paratuberculosis antigens, CD4+ cells from infected calves proliferated, produced IFN-γ, and increased expression of CD26 and CD45RO (indicative of an activated memory phenotype). Utilizing a lipoarabinomannan-based enzyme-linked immunosorbent assay, specific serum immunoglobulin was detected as early as 134 days postchallenge and generally increased after this time point. Two antigens of ∼50 and ∼60 kDa were particularly immunodominant early in infection, as shown by immunoblot with serum collected within 2 weeks postchallenge. Findings indicate that the intratonsillar inoculation route will prove useful as an experimental model for paratuberculosis infection. Additionally, this study confirms that mycobacteria-specific antibody is detectable early in the course of experimental Johne's disease, even preceding the development of specific cell-mediated responses.


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