Protection Efficacy of Oral Bait Probiotic Vaccine Constitutively Expressing Tetravalent Toxoids against Clostridium perfringens Exotoxins in Livestock (Rabbits)

Jing Bai,Xinyuan Qiao,Yigang Xu,Shuo Jia,Li Wang,Xinning Huang,Bing Han,Meijing Han,Yijing Li,Yingying Ma

doi:10.3390/vaccines8010017

Jing Bai, Xinyuan Qiao + Show 8 more

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https://doi.org/10.3390/vaccines8010017

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Journal: Vaccines	Publication Date: Jan 8, 2020
Citations: 11	License type: CC BY 4.0

Affiliation: Northeast Agricultural University, Westlake University

Abstract

Clostridium perfringens is an opportunistic pathogen. Its main virulence factors are exotoxins, which are the etiological agents of enteritis necroticans and enterotoxemia caused in livestock (cattle, sheep, and rabbits). Here, we demonstrated effective immune protection for rabbits against α, β, and ε exotoxins of C. perfringens provided by an oral tetravalent bait probiotic vaccine delivering α, ε, β1, and β2 toxoids of C. perfringens. Results showed that the recombinant probiotic had good segregational stability and good colonization ability in the rabbit intestinal tract. Oral administration of the probiotic vaccine can effectively elicit significant levels of antigen-specific mucosa sIgA and sera IgG antibodies with exotoxin-neutralizing activity. Additionally, oral immunization with the probiotic vaccine effectively promoted lymphoproliferation and Th1/Th2-associated cytokine production. The protection rate of immunized rabbits with the probiotic vaccine was 80% after challenging rabbits with a combination of C. perfringens (toxinotypes A, C, and D) and exotoxin mixture, which was better than the 60% provided by a commercial inactivated C. perfringens A, C, and D trivalent vaccine. Moreover, obvious histopathological changes were observed in the intestinal tissues of rabbits in the commercial vaccine and PBS groups. The bait probiotic vaccine can provide effective protection against C. perfringens exotoxins, suggesting a promising C. perfringens vaccination strategy.

Highlights

Clostridium perfringens is an opportunistic pathogen that is commonly found in the gastrointestinal tract of livestock and poultry
Α, β, and ε are the most important pathogenic factors of C. perfringens. α-toxin is excreted by all C. perfringens toxinotypes, and it is the only exotoxin produced by toxinotype A. α-toxin has phospholipase and sphingomyelinase activities, and it can cause hemolysis, tissue necrosis, edema, and other effects [6,7]. β-toxin, known as β1-toxin, is a key lethal virulence factor mainly produced by C. perfringens toxinotype B
The constitutive enhanced green fluorescent protein (EGFP) marker expression by the recombinant strain cultured in normal MRS medium without the presence of any inducers was first identified using ultra-high-resolution microscopy

Summary

Introduction

Clostridium perfringens is an opportunistic pathogen that is commonly found in the gastrointestinal tract of livestock and poultry. It is a Gram-positive, anaerobic, rod-shaped, and spore-forming bacterium that is the major causative agent of enteritis necroticans and enterotoxemia in animals. Β-toxin, known as β1-toxin, is a key lethal virulence factor mainly produced by C. perfringens toxinotype B and C, which has strong neurotoxicity, lethality, and necrotic effects. It can cause fatal hemorrhagic enterocolitis and enterotoxemia [8]. It can cause fatal hemorrhagic enterocolitis and enterotoxemia [8]. β2-toxin, which has similar biological activities to β1-toxin, can cause gastrointestinal diseases [9]. ε-toxin, which is produced by C. perfringens toxinotypes B and

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