Recombinant<i>Bacillus subtilis</i>Expressing the<i>Clostridium perfringens</i>Alpha Toxoid Is a Candidate Orally Delivered Vaccine against Necrotic Enteritis

Hoang, Tran Huy; Hong, Huynh A.; Clark, Graeme C.; Titball, Richard W.; Cutting, Simon M.

doi:10.1128/iai.00686-08

Cited by 83 publications

(52 citation statements)

References 40 publications

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“…It is possible that our prototype vaccines simply do not elicit sufficiently high toxin B-neutralizing titers, possibly due to B15-24 being displayed in a partially denatured form that impairs the generation of appropriate neutralizing antibodies. This may reflect the action of its fusion partner, the spore coat protein CotB, although this has been used successfully previously (8,13). Full protection to challenge using PP108 spores might be achieved either by changing the dosing regimen or by increasing the dose of heterologous protein expression (whether of A26-39 and/or of B15-24).…”

Section: Discussionmentioning

confidence: 99%

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Immunization with Bacillus Spores Expressing Toxin A Peptide Repeats Protects against Infection with Clostridium difficile Strains Producing Toxins A and B

et al. 2011

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). Thus, although many strains produce both toxins, antibodies to only toxin A can mediate protection. Animals vaccinated with recombinant spores were fully able to survive reinfection, a property that is particularly important for a disease with which patients are prone to relapse. We show that mucosal immunization, not parenteral delivery, is required to generate secretory IgA and that production of these neutralizing polymeric antibodies correlates with protection. This work demonstrates that an effective vaccine against C. difficile can be designed around two attributes, mucosal delivery and the repeat domain of toxin A.

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Section: Discussionmentioning

confidence: 99%

“…In experiments using spores expressing antigens on their surface coats, they have been shown to protect mice immunized against tetanus toxin from Clostridium tetani (8) and Clostridium perfringens alpha toxin (13). In both cases, significant levels of local immunity (sIgA) were induced.…”

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Immunization with Bacillus Spores Expressing Toxin A Peptide Repeats Protects against Infection with Clostridium difficile Strains Producing Toxins A and B

et al. 2011

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“…Practical delivery methods, such as infeed, drinking water or spray application, have not yet been tested. Recombinant B. subtilis endospores that express the C-terminal domain of alpha toxin have been used to vaccinate mice against C. perfringens infection (Hoang et al, 2008). The endospores appear to provide an adjuvant effect, boosting the immune response to the antigens.…”

Section: The Future Of Vaccine Delivery and Immunization Methods For mentioning

confidence: 99%

“…While Salmonella strains are thus potential vaccine carriers for C. perfringens proteins, there are other possibilities that, although not yet explored for protection of poultry against necrotic enteritis, may be of value. The expression of the C-terminal domain of alpha toxin on the surface of Bacillus subtilis spores was described and shown to be immunogenic in mice (Hoang et al, 2008). Lactic acid bacteria can be used as vaccine carriers for Clostridium antigens (Robinson et al, 1997(Robinson et al, , 2004.…”

Section: An Overview Of Vaccination Studies Against Necrotic Enteritismentioning

confidence: 99%

Progress and problems in vaccination against necrotic enteritis in broiler chickens

et al. 2014

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Necrotic enteritis in broilers is caused by Clostridium perfringens type A strains that produce the NetB toxin. Necrotic enteritis is one of the gastrointestinal diseases in poultry that has gained worldwide importance during the last decade due to efforts to improve broiler performance. Prevention strategies include avoiding predisposing factors, such as coccidiosis, and in-feed supplementation with a variety of feed additives. However, vaccination with modified toxin or other secreted immunogenic proteins seems a logical preventive tool for protection against a toxin-producing bacterium. Formalin-inactivated crude supernatant has been used initially for vaccination. Several studies have been carried out recently to identify the most important immunogenic and protective proteins that can be used for vaccination. These include the NetB toxin, as well as a number of other proteins. There is evidence that immunization with single proteins is not protective against severe challenge and that combinations of different antigens are needed. Most published studies have used multiple dosage vaccination regimens that are not relevant for practical use in the broiler industry. Single vaccination regimens for 1-day-old chicks appear to be non-protective. This review describes the history of vaccination strategies against necrotic enteritis in broilers and gives an update on future vaccination strategies that are applicable in the field. These may include breeder hen vaccination, in ovo vaccination and live attenuated vectors to be used in feed or in drinking water

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“…Επί σης, ο εμβολιασμός μυών με το καρβοξυλικό άκρο (C terminal domain) της τοξίνης -α διέγειρε το ανο σοποιητικό σύστημα και προκάλεσε την παραγωγή εξουδετερωτικών αντισωμάτων, τα οποία ήταν προ στατευτικά έναντι της μόλυνσης με C. perfringens (Hoang et al 2008, Zekarias et al 2008). …”

Section: δεδομένα που ενισχύουν τον ρόλο της τοξίνης -α στην παθογένεunclassified

Update on the emergence and pathogenesis of necrotic enteritis in broiler chickens

Tsiouris

Georgopoulou

Petridou

2018

J Hellenic Vet Med Soc

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Necrotic enteritis (NE) is a disease of broiler chickens, which is caused by Clostridiumperfringens type A or C and is characterized by high mortality and severe intestinal lesions. NE is described as a disease of high economical importance which affects health and welfare of broilers and also may pose a threat to public health. Although NE was known as a disease since 1930, it did not cause serious problems to the poultry industry. The emergence of the disease occurred after 1986 in Scandinavia and 2000 in the European Union and was related with the ban of in-feed antimicrobial growth promoter. Furthermore, the ban of meat meal and bone meal from the feed of broiler chickens and their replacement by fishmeal increased further the occurrence of NE. NE breaks the Koch's postulate, which supports that "a disease-causing organism should not be present in healthy individuals", because C perfringens may be detected in high populations in the gut of birds with no visible signs of NE. Moreover, challenge of birds with C perfringens does not \eadperse to the development of the disease. It is very well accepted that NE is a multi-factorialdisease in which a number of co-factors are usually required for the proliferation and toxinogenesis of C. perfringens and manifestation of the disease. Toxin -a, since 2006, has been proposed to be the main virulence factor for NE in poultry. The origin of this assumption seems to lie to observation that crude supernatant from C perfringens type A cultures induced necrotic lesions in broilers. Moreover, the development of NE lesions prevented partially by antibodies against C. perfringens toxin -a. The interpretation of these early studies is not clear, because they used crude supernatant and the assumption was made that the effects were caused by the dominant protein present (i.e. toxin -a). However, many other proteins are also present in the supernatant ofC perfringens cultures. The most convincing evidence, that toxin -a is not essential virulence factor for the pathogenesis of NE, comes from studies using a toxin -a negative mutant (epa mutant) of a C perfringens strain from NE outbreak, which was able to produce characteristic NE lesions. Recently, netB, a novel toxin that is associated with broiler NE, has been described. A netB mutant of C perfringens was unable to cause necrotic lesions in the gut of experimentally infected broilers, but a complemented netB mutant was virulent, like the wild-type strain. However, netB per se, might not be an essential component of virulence factor for the pathogenesis of NE, because not all strains isolated from diseased birds carry the netB gene. The presence of the toxin -β2, although it has been linked with increased incidence of bovine enterotoxaemia, intestinal disorders in human, horses and diarrhea in piglets, does not seem to be involved in the pathogenesis of NE in broiler. Most C. perfringens strains isolated from cases of NE do not carry the gene (cpb2) which is responsible for the production of toxin -β2. The efficacy of antitoxin -a toxoid vaccines, the high concentration of toxin-a at the supernatant of C. perfringens culture and feces of diseased birds, as well as the high titer of antibodies against toxin-a in birds with NE, indicate that toxin -a definitely play a role, major or minor, on the pathogenesis of NE in broilers.

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RecombinantBacillus subtilisExpressing theClostridium perfringensAlpha Toxoid Is a Candidate Orally Delivered Vaccine against Necrotic Enteritis

Cited by 83 publications

References 40 publications

Immunization with Bacillus Spores Expressing Toxin A Peptide Repeats Protects against Infection with Clostridium difficile Strains Producing Toxins A and B

Immunization with Bacillus Spores Expressing Toxin A Peptide Repeats Protects against Infection with Clostridium difficile Strains Producing Toxins A and B

Progress and problems in vaccination against necrotic enteritis in broiler chickens

Update on the emergence and pathogenesis of necrotic enteritis in broiler chickens

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