Variable protection against experimental broiler necrotic enteritis after immunization with the C-terminal fragment of<i>Clostridium perfringens</i>alpha-toxin and a non-toxic NetB variant

Costa, Sérgio P. Fernandes da; Mot, Dorien; Geeraerts, Sofie; Bokori-Brown, Monika; Immerseel, Filip Van; Titball, Richard W.

doi:10.1080/03079457.2015.1129663

Cited by 30 publications

(25 citation statements)

References 44 publications

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“…Remarkably, immunization with NetB toxin, which is essential to cause disease in broilers, does not afford higher levels of protection than vaccination with other toxins or proteins. However, when birds were vaccinated either via the parenteral or the oral route, with a combination of both NetB toxin and alpha toxin, higher levels of protection were obtained [ 107 , 108 ]. In order to obtain full protection against C. perfringens -induced enteric diseases, not only antibodies that inhibit toxin activity might be needed; a combination of antigens targeting also bacterial proliferation, colonization and/or nutrient acquisition could be more efficient than either one of the individual approaches.…”

Section: Vaccination Strategies To Reduce Antibiotic Use For Diseasesmentioning

confidence: 99%

Vaccines as alternatives to antibiotics for food producing animals. Part 2: new approaches and potential solutions

Hoelzer

Bielke²,

Blake

et al. 2018

Vet Res

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Vaccines and other alternative products are central to the future success of animal agriculture because they can help minimize the need for antibiotics by preventing and controlling infectious diseases in animal populations. To assess scientific advancements related to alternatives to antibiotics and provide actionable strategies to support their development, the United States Department of Agriculture, with support from the World Organisation for Animal Health, organized the second International Symposium on Alternatives to Antibiotics. It focused on six key areas: vaccines; microbial-derived products; non-nutritive phytochemicals; immune-related products; chemicals, enzymes, and innovative drugs; and regulatory pathways to enable the development and licensure of alternatives to antibiotics. This article, the second part in a two-part series, highlights new approaches and potential solutions for the development of vaccines as alternatives to antibiotics in food producing animals; opportunities, challenges and needs for the development of such vaccines are discussed in the first part of this series. As discussed in part 1 of this manuscript, many current vaccines fall short of ideal vaccines in one or more respects. Promising breakthroughs to overcome these limitations include new biotechnology techniques, new oral vaccine approaches, novel adjuvants, new delivery strategies based on bacterial spores, and live recombinant vectors; they also include new vaccination strategies in-ovo, and strategies that simultaneously protect against multiple pathogens. However, translating this research into commercial vaccines that effectively reduce the need for antibiotics will require close collaboration among stakeholders, for instance through public–private partnerships. Targeted research and development investments and concerted efforts by all affected are needed to realize the potential of vaccines to improve animal health, safeguard agricultural productivity, and reduce antibiotic consumption and resulting resistance risks.

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Section: Vaccination Strategies To Reduce Antibiotic Use For Diseasesmentioning

confidence: 99%

Vaccines as alternatives to antibiotics for food producing animals. Part 2: new approaches and potential solutions

Hoelzer

Bielke²,

Blake

et al. 2018

Vet Res

Self Cite

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“…There are some evidences that the Tpel have little effect on pathogenesis of NE and induces partial protection against NE [7,8]. However, there is no consensus in this regard and some researchers believe that it increases virulence of C. perfringens while others found no evidence of involving Tpel in the NE pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies demonstrated that immunizing ability for protection against NE was associated with several virulence factors. The most important of these virulence factors are phospholipase C known as Alpha-toxin, β-pore forming toxin, NetB, and a zinc metallopeptidase protein [7,8,28]. Utilizing a fusion of non toxic variants of these proteins as a recombinant subunit vaccine candidate could enhance protective immunity [31,6].…”

Section: Introductionmentioning

confidence: 99%

Design and Expression Optimization of a Chimeric Derivative of NetB, Alpha-Toxin and Metallopeptidase Proteins as a Subunit Vaccine Against Clostridium perfringens

Katalani¹,

Nematzadeh

Ahmadian

et al. 2019

vacres

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Avian necrotic enteritis (NE) is a multi-virulence disease caused by the bacterium Clostridium perfringens. Several toxins of this bacteria are components of different candidate vaccines, and have been considered as important factors in pathogenesis of NE. A fusion subunit protein composed of immunodominant segments of NetB, Alpha-toxin and metallopeptidase proteins (NAM) was designed. The high level production of NE subunit vaccine candidate is important for the in vitro and in vivo evaluation and later to decrease the production costs. Therefore, the Response Surface Methodology (RSM) was used for optimizing E. coli culture condition. To this end, induction conditions including cell optical density prior induction (OD600nm), IPTG concentration, post-induction temperature and time were modified. The statistical analysis revealed that all variables except IPTG had significant effects on production and solubility of rNAM. A 7.39 fold increase in production of soluble rNAM was achieved when the post induction temperature, IPTG concentration, the pre-induction OD and time were 19 ºC, 0.55 mM, 0.8 respectively in 8 h after induction. Our study indicated that the RSM method is a simple and superior strategy for protein expression improvement which is considered as a major limitation in production of vaccine candidate and other recombinant proteins using different hosts. Katalani1 et al Design and Expression Optimization of a Chimeric … * Recombinant NAM concentration yield (mg/L) obtained from densitometry analysis with different expression conditions of IPTG concentration, OD600, temperature and induction time using a central composite design for four variables.

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“…PE is the most abundant phospholipid present in intestinal epithelial cells (39) and is therefore a probable nutrient source during lesion formation at the intestinal mucosa, where C. perfringens cells are present in high numbers. PE can also be hydrolyzed by CPA (40), a zinc metallophospholipase C that, although no longer considered to be the key toxin involved (41), still appears to play a role in NE pathogenesis (42)(43)(44). Ethanolamine has been specifically implicated in virulence, due to its ability to serve as a sole carbon and nitrogen source for some bacterial pathogens, including C. perfringens (45).…”

Section: Discussionmentioning

confidence: 99%

The Agr-Like Quorum Sensing System Is Required for Pathogenesis of Necrotic Enteritis Caused by Clostridium perfringens in Poultry

Lepp

Gohari

et al. 2017

Infect Immun

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Clostridium perfringens encodes at least two different quorum sensing (QS) systems, the Agr-like and LuxS, and recent studies have highlighted their importance in the regulation of toxin production and virulence. The role of QS in the pathogenesis of necrotic enteritis (NE) in poultry and the regulation of NetB, the key toxin involved, has not yet been investigated. We have generated isogenic agrB-null and complemented strains from parent strain CP1 and demonstrated that the virulence of the agrB-null mutant was strongly attenuated in a chicken NE model system and restored by complementation. The production of NetB, a key NE-associated toxin, was dramatically reduced in the agrB mutant at both the transcriptional and protein levels, though not in a luxS mutant. Transwell assays confirmed that the Agrlike QS system controls NetB production through a diffusible signal. Global gene expression analysis of the agrB mutant identified additional genes modulated by Agrlike QS, including operons related to phospholipid metabolism and adherence, which may also play a role in NE pathogenesis. This study provides the first evidence that the Agr-like QS system is critical for NE pathogenesis and identifies a number of Agr-regulated genes, most notably netB, that are potentially involved in mediating its effects. The Agr-like QS system thus may serve as a target for developing novel interventions to prevent NE in chickens.KEYWORDS NetB, Clostridium perfringens, Agr-like quorum sensing, LuxS, VirS/VirR, necrotic enteritis, poultry, quorum sensing C lostridium perfringens is a Gram-positive, spore-forming, anaerobic bacterium that is widely distributed in soil, feces, and foods as well as the normal intestinal microbiota of both humans and animals (1). C. perfringens is responsible for a number of human and animal diseases owing to an arsenal of at least 16 different extracellular toxins, including food poisoning, gas gangrene in humans, enterotoxemia of sheep and goats, lamb dysentery, and necrotic enteritis (NE) in poultry (2). Strains are classified into five toxinotypes (A to E) based on the production of four major typing toxins (alpha-, beta-, epsilon-, and iota-toxin) (3, 4).Certain type A strains can produce NE, an enteric disease of poultry that, in 2015, was estimated to cost the worldwide poultry industry nearly $6 billion in losses (5). The disease occurs when C. perfringens proliferates to high numbers in the intestinal tract and produces extracellular toxins, resulting in characteristic necrotic lesions and often high rates of mortality (6, 7). In addition to producing alpha-toxin (CPA), which is carried

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Variable protection against experimental broiler necrotic enteritis after immunization with the C-terminal fragment ofClostridium perfringensalpha-toxin and a non-toxic NetB variant

Cited by 30 publications

References 44 publications

Vaccines as alternatives to antibiotics for food producing animals. Part 2: new approaches and potential solutions

Vaccines as alternatives to antibiotics for food producing animals. Part 2: new approaches and potential solutions

Design and Expression Optimization of a Chimeric Derivative of NetB, Alpha-Toxin and Metallopeptidase Proteins as a Subunit Vaccine Against Clostridium perfringens

The Agr-Like Quorum Sensing System Is Required for Pathogenesis of Necrotic Enteritis Caused by Clostridium perfringens in Poultry

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