Reducing Campylobacter jejuni colonization in broiler chickens by in-feed supplementation with hyperimmune egg yolk antibodies.

Campylobacter infections sourced mainly to poultry products, are the most important bacterial foodborne zoonoses worldwide. No effective measures to control these infections in broiler production exist to date. Here, we used passive immunization with hyperimmune egg yolks to confer broad protection of broilers against Campylobacter infection. Two novel vaccines, a bacterin of thirteen Campylobacter jejuni (C. jejuni) and C. coli strains and a subunit vaccine of six immunodominant Campylobacter antigens, were used for the immunization of layers, resulting in high and prolonged levels of specific immunoglobulin Y (IgY) in the hens' yolks. In the first in vivo trial, yolks (sham, bacterin or subunit vaccine derived) were administered prophylactically in the broiler feed. Both the bacterin- and subunit vaccine-induced IgY significantly reduced the number of Campylobacter-colonized broilers. In the second in vivo trial, the yolks were administered therapeutically during three days before euthanasia. The bacterin IgY resulted in a significant decrease in C. jejuni counts per infected bird. The hyperimmune yolks showed strong reactivity to a broad representation of C. jejuni and C. coli clonal complexes. These results indicate that passive immunization with hyperimmune yolks, especially bacterin derived, offers possibilities to control Campylobacter colonization in poultry.

In vitro efficacy of potentiated egg yolk powder against Campylobacter jejuni does not correlate with in vitro efficacy.

Campylobacter jejuni is a zoonotic agent responsible for the foodborne gastroenteritis campylobacteriosis. Control of C. jejuni load in the poultry primary production is recognized as an avenue to reduce human exposure to the pathogen. As for now, no commercially applicable control methods exist at the farm. Several studies tested egg yolk powders, potentiated or not against C. jejuni, as feed additives for chicken and suggested that the quantity and quality of the antibodies presence in the yolk are determinant factors for the full success of this approach. Unfortunately, data from these studies inconsistently showed a reduction of cecal C. jejuni carriage. Our first goal wwas to characterize (quantification by ELISA, agglutination test, bacterial antigen recognition profiles by Western blot, bactericidal effect by serum killing assays and C. jejuni mobility by soft agar migation) the antibodies extracted from egg yolk powders originating from different egg production protocols. Secondly, these powders were microencapsulated and recharacterized. Finally the protected powders were tested as a feed additive to destabilize C. jejuni colonization in an in vivo assay. Despite the in vitro results indicating the ability of the egg yolk powders to recognize Campylobacter and potentially alter its colonization of the chicken caecum, these results were not confirmed in the in vivo trial despite that specific caecal IgY directed toward Campylobacter were detected in the groups receiving the protected powders. More research is needed on Campylobacter in order to effectively control this pathogen at the farm.

Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part II: Vaccines for Shigella, Salmonella, enterotoxigenic E. coli (ETEC) enterohemorragic E. coli (EHEC) and Campylobacter jejuni.

In Part II we discuss the following bacterial pathogens: Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic) and Campylobacter jejuni. In contrast to the enteric viruses and Vibrio cholerae discussed in Part I of this series, for the bacterial pathogens described here there is only one licensed vaccine, developed primarily for Vibrio cholerae and which provides moderate protection against enterotoxigenic E. coli (ETEC) (Dukoral(®)), as well as a few additional candidates in advanced stages of development for ETEC and one candidate for Shigella spp. Numerous vaccine candidates in earlier stages of development are discussed.

Beneficial effect of Eucommia polysaccharides on systemic lupus erythematosus-like syndrome induced by Campylobacter jejuni in BALB/c mice.

The stem bark of Eucommia ulmoides Oliv. is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia in traditional Chinese medicine. This study was to determine whether the crude polysaccharides (EUPs) isolated from the stem bark of E. ulmoides had beneficial effects on lupus-like syndrome in mice. BALB/c mice were immunized with CJ-S(131) in Freund's complete adjuvant on day 0, and then boosted on day 14. EUPs 15 or 30 mg kg(-1)·day(-1), or prednisone 5 mg kg(-1)·day(-1) was given to BALB/c mice intragastrically from day 0 to 34. Treatment with EUPs 15 or 30 mg kg(-1)·day(-1) for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. These findings suggested that Eucommia polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndrome induced by CJ-S(131) in BALB/c mice.

Novel anti-idiotype antibody therapy for lipooligosaccharide-induced experimental autoimmune neuritis: use relevant to Guillain-Barré syndrome.

Campylobacteriosis is a frequent antecedent event in Guillain-Barré syndrome (GBS), inducing high-titer serum antibodies for ganglioside antigens in the peripheral nervous system (PNS). Molecular mimicry between the lipooligosaccharide (LOS) component of Campylobacter jejuni and human peripheral nerve gangliosides is believed to play an important role in the pathogenesis of GBS. Conventional treatment strategies for patients with GBS include plasmapheresis, intravenous immunoglobulin (IVIG), and immunosuppression, which are invasive or relatively ineffective. In this study, we used our animal model of GBS, in which Lewis rats were immunized with GD3-like LOS isolated from C.jejuni. The animals developed anti-GD3 ganglioside antibodies and manifested neuromuscular dysfunction. To develop novel therapeutic strategies, we treated the animals by intraperitoneal administration of an anti-GD3 antiidiotype monoclonal antibody (BEC2) that specifically interacts with the pathogenic antibody. The treated animals had a remarkable reduction of anti-GD3 antibody titers and improvement of motor nerve functions. The results suggest that ganglioside mimics, such as antiidiotype antibodies, may be powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic antiganglioside antibodies.

Effects of esculentoside A on autoimmune syndrome induced by Campylobacterjejuni in mice and its modulation on T-lymphocyte proliferation and apoptosis.

Esculentoside A (EsA), a saponin isolated from the root of Phytolacca esculenta, has been reported to exert anti-inflammatory effects in several animal models of acute and chronic inflammation by inhibiting the production and activity of pro-inflammatory cytokines in macrophages and epithelial cells. However, little is known about its modulation on T cells. In the present study, we further investigated its potential in treatment of autoimmune disease and its modulation on T cells, using an experimental autoimmune model established through immunizing mice with Campylobacterjejuni strain CJ-S(131) in Freund's complete adjuvant. Our results demonstrated that EsA administration markedly alleviated the inflammatory injury in liver and kidney of model mice, decreased the anti-CD3/CD28-stimulated proliferation of splenocytes and lymph node cells, and reduced the percentage of CD3+, CD4+, and CD8+ lymphocytes in peripheral blood. Furthermore, we demonstrated that EsA induced apoptosis in ConA-activated thymocytes but not in non-activated thymocytes. Gene expression analysis revealed that EsA up-regulated the expression of a group of pro-apoptotic genes more profoundly in Con A-activated thymocytes than in non-activated thymocytes. EsA-affected pro-apoptotic genes included those involved in Fas induction, p53 activation, redox metabolism, calcium- and glucocorticoid-induced apoptosis signals, suggesting that EsA may modulate multiple apoptotic signal pathways in activated T cells. Taken together, our findings suggest that EsA may be useful for the treatment of autoimmune disease through modulation on T cell-mediated adaptive immunity.

Beneficial effect of Bupleurum polysaccharides on autoimmune disease induced by Campylobacter jejuni in BALB/c mice.

AIM OF THE STUDY: Radix Bupleuri, is one of the most frequently prescribed crude herbs in the prescriptions of traditional Chinese medicine for the treatment of inflammatory diseases and auto-immune diseases. This study was to determine whether the crude polysaccharides (BPs) isolated from the roots of Bupleurum smithii var. parvifolium, had beneficial effects on autoimmune disease. MATERIALS AND METHODS: BALB/c mice were immunized with CJ-S(131) in Freund's complete adjuvant on day 0, and then boosted on day 14. BPs 15 or 30 mg kg(-1) day(-1), or prednisone 5 mg kg(-1) day(-1) was given to BALB/c mice intragastrically from day 0 to day 34. RESULTS: Treatment with BPs 15 or 30 mg kg(-1) day(-1) for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. BPs 30 mg kg(-1) day(-1) improved weight loss and spleen swelling when compared with vehicle-treated group. CONCLUSIONS: These findings suggested that Bupleurum polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndroma induced by CJ-S(131) in BALB/c mice.

[Immune-pharmacology study on the immunoregulatory effects of Dabuyin Wan in autoimmune mice induced by Campylobacter jejuni].

OBJECTIVE: To study the immunoregulatory effect of Dabuyin Wan (DBYW) on cytokines of IFN-gamma and IL-4 and proliferation of T, B lymphocytes in autoimmune mice induced by Campylobacter jejuni. METHODS: Healthy female ICR mice were divided into 8 groups at random: normal control group (N), model group (M), model control group (MC), five different time administration groups (30 min, 1h, 1.5h, 2h, 3h). The mice were induced by Campylobacter jejuni with Complete Freund's Adjuvant as autoimmune animal model except N group. From the fifteenth day after primary immunization, the administration groups were given DBYW through gastric route in a dosage of 0.4 g/ml. At the same time, MC group were given physiological saline instead. All the administration lasted for 10 days. Blood samples were taken 30 min, 1h, 1.5h, 2h and 3h respectively after the last administration to detect the proliferation of T, B lymphocytes and to cultivate T lymphocytes which were taken from M group. The concentrations of gamma-interferon (IFN-gamma) and interleukin-4 (IL-4) in culture supernantants were measured by an enzyme-linked immunosorbent asay (ELISA) after 48h. The drug efficacy was evaluated by marking the curve of time-effect relationship in the chart. RESULTS: It was found that the concentrations of IFN-gamma was significantly lower in cultures with the drug-containing serum taken at 1-1.5 h after the treatment than that in cultures with the MC control serum (P < 0.01). Only the serum taken at 1.5h was found to enhance the production of IL-4 (P < 0.05). The proliferation of T, B lymphocytes was markedly inhibited by the drug-containing serum taken at 1-1.5 h after the treatment (P < 0.01). CONCLUSION: The drug-containing serum in mice taken at 1-1.5 h after ingestion of DBYW can regulate the immunologic function of autoimmune mice induced by Campylobacter jejuni.

Secretion of the virulence-associated Campylobacter invasion antigens from Campylobacter jejuni requires a stimulatory signal.

Campylobacter jejuni are a common cause of human diarrheal illness. Previous work has demonstrated that C. jejuni synthesize a novel set of proteins upon coculturing with epithelial cells, some of which are secreted. The secreted proteins have been collectively referred to as Campylobacter invasion antigens (Cia proteins). Metabolic labeling experiments revealed that Cia protein synthesis and secretion are separable and that secretion is the rate-limiting step of these processes. Additional work indicated that Cia protein synthesis is induced in response to bile salts and various eukaryotic host cell components. Host cell components also can induce Cia protein secretion. Culturing C. jejuni on plates supplemented with the bile salt deoxycholate retarded the inhibitory effect of chloramphenicol on C. jejuni invasion, as judged by the gentamicin-protection assay. These data suggest that the coordinate expression of the genes encoding the Cia proteins is subject to environmental regulation.

[Intervention of Campylobacter jejuni subsp. jejuni flagella in the adhesion to cellular cultures: bacteriological and immunological evidence]. / Intervención del flagelo de Campylobacter jejuni subsp. jejuni en la adherencia a cultivos celulares: evidencias bacteriológicas e inmunológicas.

The participation of the flagella of a virulent strain (O52) of Campylobacter jejuni subsp. jejuni in the adhesion to HEp-2 cells and their inhibition by means of homologous polyclonal antibodies, monoclonal anti-flagella antibodies and colostral natural antibodies (IgA) was studied. An aflagellated strain (T1) was used as negative control. Adhesion was observed in higher rates with O52 strain (72%) than with T1 strain (27.5%). Polyclonal, monoclonal and colostral antibodies inhibited O52 strain adhesion in more than 70% (p < 0.001). T1 strain adhesion was inhibited only by polyclonal and colostral natural antibodies. Our results suggest that the flagella of C. jejuni subsp. jejuni could participate effectively in the adhesion process. However, the inhibition of T1 strain by polyclonal and colostral antibodies suggests the existence of other binds of adhesins in the bacterial surface.

Intervención del flagelo de campylobacter jejuni subsp. jejuni en la adherencia a cultivos celulares: evidencias bacteriológicas e inmunológicas / Intervention of campylobacter campylobacter jejuni subsp. jejuni flagella in the adhesion to cellular cultures: bacteriological and immunological evidences

The participation of the flagella of a virulent strain (O52) of campylobacter jejuni subsp. jejuni in the adhesion to HEp-2 cells and their inhibition by means of homologous polyclonal antibodies, moniclonal antiflagella antibodies and colostral natural antibodies (IgA) was studied. An aflagellated strain (T1) was used as negative control. Adhesion was observed in higher rates with O52 strain (72 percent) than with T1 strain (27,5 percent). Polyclonal, monoclonal and colostral antibodies inhibited O52 strain adhesion in more than 70 percent (p<0,001). T1 strain adhesion was inhibited only by polyclonal and colostral natural antibodies. Our results suggest that the flagella of C. jejuni subsp. jejuni could participate effectively in the adhesion process. However, the inhibition of T1 strain by polyclonal and colostral antibodies suggest the existence of other kinds of adhesins in the bacterial surface

Production of hyperimmune bovine colostrum against Campylobacter jejuni.

Serial immunization of dairy cows with Campylobacter jejuni resulted in an enhanced serum antibody response and production of hyperimmune colostrum in all vaccinated animals. An approximate 10-fold decrease in the Camp. jejuni-specific antibody titres in colostrum was observed within 2 d post-partum. The lyophilized colostral concentrate fed to newborn calves resulted in a rapid increase in serum antibody response. Specific Camp. jejuni immunoglobulins could be detected in these animals for a further 10 weeks. The lyophilized hyperimmunized colostrum was very stable in vitro at different storage temperatures. It could be used for passive immunization to campylobacteriosis.