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研发两种针对艰难梭菌感染的重组疫苗及其在妊娠母猪和新生仔猪中的免疫原性。

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

机构信息

Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

出版信息

Anaerobe. 2024 Oct;89:102896. doi: 10.1016/j.anaerobe.2024.102896. Epub 2024 Aug 8.

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.

摘要

简介

艰难梭菌是人类抗生素相关性腹泻的主要病原体,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)引起的结肠病变导致腹泻和严重的生产损失。

目的

本研究旨在从 TcdA 和 TcdB 的免疫原性 C 端片段中开发两种重组疫苗,并评估其在兔和种猪中的免疫反应。生产了两种疫苗:双价(rAB),由 TcdA 和 TcdB 的重组片段组成,嵌合(rQAB),对应于在单个蛋白中合成相同片段。用铝佐剂或 0.85%无菌生理盐水将 10 或 50μg 蛋白作为佐剂加入到 1mL 终体积中,给兔分组接种。用 ELISA 法检测免疫了 rAB 和 rQAB 疫苗的兔和母猪的抗 TcdA 和抗 TcdB IgG 抗体。用 20μg/剂量对免疫母猪进行肌肉内接种,采用初免-加强免疫程序。

结果

免疫母猪的不同抗体滴度(p≤0.05)(rAB 和 rQAB 疫苗)与对照组不同。此外,与对照组仔猪相比,来自免疫母猪的新生仔猪也对 TcdA 和 TcdB IgGs 呈阳性(p≤0.05)。rQAB 疫苗免疫母猪可诱导仔猪产生更高的抗 TcdA 和抗 TcdB 反应,表明该化合物优于 rAB。

结论

合成的重组蛋白能够在母猪中诱导针对艰难梭菌毒素 A 和 B 的抗体滴度,并通过初乳被动传递给仔猪。

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