Development of two recombinant vaccines against Clostridioides difficile infection and immunogenicity in pregnant sows and neonatal piglets

IF 2.5 3区 生物学 Q3 MICROBIOLOGY Anaerobe Pub Date : 2024-08-08 DOI:10.1016/j.anaerobe.2024.102896
Carolina P. Ramos , Williane F. Siqueira , Laila A. Viana , João L.R. Cunha , Ricardo T. Fujiwara , Victor S. Amarante , Thayanne G.V. Souza , Rodrigo O.S. Silva
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Abstract

Introduction

Clostridioides difficile is the main cause of antibiotic-associated diarrhea in humans and is a major enteropathogen in several animal species. In newborn piglets, colonic lesions caused by C. difficile A and B toxins (TcdA and TcdB, respectively) cause diarrhea and significant production losses.

Objective

The present study aimed to develop two recombinant vaccines from immunogenic C-terminal fragments of TcdA and TcdB and evaluate the immune response in rabbits and in breeding sows. Two vaccines were produced: bivalent (rAB), consisting of recombinant fragments of TcdA and TcdB, and chimeric (rQAB), corresponding to the synthesis of the same fragments in a single protein. Groups of rabbits were inoculated with 10 or 50 μg of proteins adjuvanted with aluminum or 0.85 % sterile saline in a final volume of 1 mL/dose. Anti-TcdA and anti-TcdB IgG antibodies were detected in rabbits and sows immunized with both rAB and rQAB vaccines by ELISA. The vaccinated sows were inoculated intramuscularly with 20 μg/dose using a prime-boost approach.

Results

Different antibody titers (p ≤ 0.05) were observed among the vaccinated groups of sows (rAB and rQAB) and control. Additionally, newborn piglets from vaccinated sows were also positive for anti-TcdA and anti-TcdB IgGs, in contrast to control piglets (p ≤ 0.05). Immunization of sows with the rQAB vaccine conferred higher anti-TcdA and anti-TcdB responses in piglets, suggesting the superiority of this compound over rAB.

Conclusion

The synthesized recombinant proteins were capable of inducing antibody titers against C. difficile toxins A and B in sows, and were passively transferred to piglets through colostrum.

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针对艰难梭菌感染的两种重组疫苗的开发以及妊娠母猪和新生仔猪的免疫原性。
导言:艰难梭菌是导致人类抗生素相关性腹泻的主要原因,也是多种动物的主要肠道病原体。在新生仔猪中,艰难梭菌 A 型和 B 型毒素(分别为 TcdA 和 TcdB)引起的结肠病变会导致腹泻和严重的生产损失:本研究旨在利用 TcdA 和 TcdB 的免疫原 C 端片段开发两种重组疫苗,并评估兔子和繁殖母猪的免疫反应。我们生产了两种疫苗:由 TcdA 和 TcdB 重组片段组成的双价疫苗(rAB)和嵌合疫苗(rQAB),前者相当于将相同片段合成为单一蛋白。每组兔子接种 10 或 50 μg 的铝或 0.85% 无菌生理盐水佐剂蛋白,最终剂量为 1 mL/次。用酶联免疫吸附试验检测使用 rAB 和 rQAB 疫苗免疫的兔子和母猪体内的抗 TcdA 和抗 TcdB IgG 抗体。接种后的母猪肌肉注射 20 μg/dose 疫苗,采用原代-加强免疫法:结果:接种母猪组(rAB 和 rQAB)与对照组的抗体滴度不同(p ≤ 0.05)。此外,接种疫苗母猪的新生仔猪抗 TcdA 和抗 TcdB IgG 也呈阳性,与对照组仔猪形成鲜明对比(p≤0.05)。用 rQAB 疫苗免疫母猪可使仔猪产生更高的抗 TcdA 和抗 TcdB 反应,表明该化合物优于 rAB:结论:合成的重组蛋白能诱导母猪产生抗艰难梭菌毒素 A 和 B 的抗体滴度,并能通过初乳被动转移给仔猪。
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来源期刊
Anaerobe
Anaerobe 生物-微生物学
CiteScore
5.20
自引率
8.70%
发文量
137
审稿时长
76 days
期刊介绍: Anaerobe is essential reading for those who wish to remain at the forefront of discoveries relating to life processes of strictly anaerobes. The journal is multi-disciplinary, and provides a unique forum for those investigating anaerobic organisms that cause infections in humans and animals, as well as anaerobes that play roles in microbiomes or environmental processes. Anaerobe publishes reviews, mini reviews, original research articles, notes and case reports. Relevant topics fall into the broad categories of anaerobes in human and animal diseases, anaerobes in the microbiome, anaerobes in the environment, diagnosis of anaerobes in clinical microbiology laboratories, molecular biology, genetics, pathogenesis, toxins and antibiotic susceptibility of anaerobic bacteria.
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