Preparation and characterization of a human scFv against the Clostridium perfringens type A alpha-toxin

Wang, Dongdong; Yu-huan, Yue; Wu, Guangmou; Tian, Yuan; Yu-ling, Liu; Yu, Jia; Yuan-gang, JI; Wang, Jinpeng; Li, Jian; Rong-rong, Pan; Ma, Hongwei; Zhang, Guoli

doi:10.1016/j.toxicon.2017.02.021

Cited by 9 publications

(5 citation statements)

References 25 publications

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“…According to the traditional C. perfringens toxin typing scheme, C. perfringens is classified into five toxin types (A, B, C, D, and E) based on the major toxins α, β, ε, and ι produced by each toxinotype [3], while a recently updated study proposed that C. perfringens strains should be classified into seven toxinotypes, A to G [4]. The α-toxin with phospholipase C and sphingomyelinase activities is a major pathogenic factor influencing C. perfringens infections that are responsible for gas gangrene in sheep [5], and humans [6], which can be produced by all toxinotypes of C. perfringens but is the only toxin produced by toxinotype A [7,8]. The β-toxin (β1-toxin) produced by toxinotype B and C is a key virulence factor of fatal hemorrhagic enterocolitis and enterotoxemia in livestock and can lead to severe intestinal bleeding and small intestinal mucosal necrosis [9,10].…”

Section: Introductionmentioning

confidence: 99%

An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ε, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity

et al. 2019

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Clostridium perfringens is a common opportunistic pathogen endangering livestock and poultry breeds. Here, using enhanced green fluorescent protein as screening marker, a recombinant lactobacillus tetravalent vaccine constitutively expressing α, ϵ, β1, and β2 toxoids of C. perfringens was developed, and its immunogenicity in mice was investigated via oral administration. This probiotic vaccine could effectively induce antigen-specific secretory IgA (sIgA)-based mucosal and IgG-based humoral immune responses, and significantly high levels (p< 0.05) of cytokines IL-2, IL-4, IL-10, IL-12, IL-17, and IFN-γ were produced in immunized mice. Moreover, lymphoproliferation and percentage of CD4+ and CD8+ T cells significantly increased in mice of the probiotic vaccine group. Challenge experiments were performed in mice with C. perfringens toxinotypes A, C, and D crude toxins to evaluate protection efficiency of the probiotic vaccine, using a commercial inactivated C. perfringens vaccine made by C. perfringens toxinotypes A, C, and D as vaccine control. We observed 80% protection rate in the probiotic vaccine group, which was higher than commercial vaccine group, whereas all mice in control groups died and obvious histopathological changes were observed in liver, spleen, kidney, and intestines of mice. Significantly, we compared the immunogenicity and protection efficiency of lactobacillus constitutive expression system and lactobacillus inducible expression system, and results showed that lactobacillus constitutive expression system has obvious advantages. Our study clearly demonstrated that the probiotics vaccine could effectively induce mucosal, humoral, and cellular immunity, and provide effective protection against C. perfringens toxins, suggesting a promising strategy for the development of oral vaccine against C. perfringens.

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Section: Introductionmentioning

confidence: 99%

An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ε, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity

et al. 2019

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“…As such, it is considered a potential bioterrorism threat. However, the pathogenesis of CPA has not yet been fully elucidated [ 37 ]. Over the past few decades, the biological activity of CPA has been tested and examined, including necrotic, lethal, phospholipase C, and sphingomyelinase activities [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Purinergic Receptor Antagonists Inhibit Hemolysis Induced by Clostridium perfringens Alpha Toxin

Guo,

Yue,

Chen

et al. 2024

Pathogens

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Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus β-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis.

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“…a Toxin is the major virulence factor of Clostridium perfringens type A, so the antibody against a toxin is the most used indicator to evaluate the vaccine effect (26). Detection of specific immunoglobulin G or SIgA was examined by indirect enzyme-linked immunosorbent assay (ELISA) according to Li et al (27) with some modifications.…”

Section: Antibody Measurementmentioning

confidence: 99%

Nano selenium-enriched probiotic Lactobacillus enhances alum adjuvanticity and promotes antigen-specific systemic and mucosal immunity

Liu

Sun²,

Sun³

et al. 2023

Front. Immunol.

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Nano selenium-enriched probiotics have been identified to improve immune responses, such as alleviating inflammation, antioxidant function, treatment of tumors, anticancer activity, and regulating intestinal flora. However, so far, there is little information on improving the immune effect of the vaccine. Here, we prepared nano selenium-enriched Levilactobacillus brevis 23017 (SeL) and heat-inactivated nano selenium-enriched L. brevis 23017 (HiSeL) and evaluated their immune enhancing functions on the alum-adjuvanted, inactivated Clostridium perfringens type A vaccine in mouse and rabbit models, respectively. We found that SeL enhanced immune responses of the vaccine by inducing a more rapid antibody production, eliciting higher immunoglobulin G (IgG) antibody titers, improving secretory immunoglobulin A (SIgA) antibody level and cellular immune response, and regulating Th1/Th2 immune response, thus helping to induce better protective efficacy after challenge. Moreover, we confirmed that the immunoenhancement effects are related to regulating oxidative stress, cytokine secretion, and selenoprotein expression. Meanwhile, similar effects were observed in HiSeL. In addition, they show enhanced humoral immune response at 1/2 and 1/4 standard vaccine doses, which confirms their prominent immune enhancement effect. Finally, the effect of improving vaccine immune responses was further confirmed in rabbits, which shows that SeL stimulates the production of IgG antibodies, generates α toxin–neutralizing antibodies rapidly, and reduces the pathological damage to intestine tissue. Our study demonstrates that nano selenium-enriched probiotics improve the immune effect of the alum adjuvants vaccine and highlight its potential usage in remedying the disadvantages of alum adjuvants.

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Preparation and characterization of a human scFv against the Clostridium perfringens type A alpha-toxin

Cited by 9 publications

References 25 publications

An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ε, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity

An EGFP-marked recombinant lactobacillus oral tetravalent vaccine constitutively expressing α, ε, β1, and β2 toxoids for Clostridium perfringens elicits effective anti-toxins protective immunity

Purinergic Receptor Antagonists Inhibit Hemolysis Induced by Clostridium perfringens Alpha Toxin

Nano selenium-enriched probiotic Lactobacillus enhances alum adjuvanticity and promotes antigen-specific systemic and mucosal immunity

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