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大型梭菌毒素:简要综述及兽用疫苗开发抗原设计见解

Large Clostridial Toxins: A Brief Review and Insights into Antigen Design for Veterinary Vaccine Development.

作者信息

Rodrigues Rodrigues Rafael, Alves Mariliana Luiza Ferreira, Bilhalva Miguel Andrade, Kremer Frederico Schmitt, Junior Clóvis Moreira, Ferreira Marcos Roberto Alves, Galvão Cleideanny Cancela, Quatrin Pedro Henrique Dala Nora, Conceição Fabricio Rochedo

机构信息

Centro de Desenvolvimento Tecnológico, Biotecnologia, Universidade Federal de Pelotas - Campus Universitário, Capão do Leão, Rio Grande Do Sul, CEP 96160-000, Brazil.

Instituto Federal Sul-Rio-Grandense, IFSul, Campus Pelotas, Pelotas, Rio Grande Do Sul, Brasil.

出版信息

Mol Biotechnol. 2024 Oct 29. doi: 10.1007/s12033-024-01303-6.

Abstract

The group of large clostridial toxins (LCTs) includes toxins A (TcdA) and B (TcdB) from Clostridioides difficile, hemorrhagic and lethal toxins from Paeniclostridium sordellii, alpha toxin from Clostridium novyi (TcnA), and cytotoxin from Clostridium perfringens. These toxins are associated with severe pathologies in livestock, including gas gangrene (P. sordellii and C. novyi), infectious necrotic hepatitis (C. novyi), avian necrotic enteritis (C. perfringens), and enterocolitis (C. difficile). Immunoprophylaxis is crucial for controlling these diseases, but traditional vaccines face production challenges, such as labor-intensive processes, and often exhibit low immunogenicity. This has led to increased interest in recombinant vaccines. While TcdA and TcdB are well-studied for human immunization, other LCTs remain poorly characterized and require further investigation. Therefore, this study emphasizes the importance of understanding lesser-explored toxins and proposes using immunoinformatics to identify their immunodominant regions. By mapping these regions using silico tools and considering their homology with TcdA and TcdB, the study aims to guide future research in veterinary vaccinology. It also explores alternatives to overcome the limitations of conventional and recombinant vaccines, offering guidelines for developing more effective vaccination strategies against severe infections in animals.

摘要

大型梭菌毒素(LCTs)组包括艰难梭菌的毒素A(TcdA)和毒素B(TcdB)、索氏梭菌的出血毒素和致死毒素、诺维氏梭菌的α毒素(TcnA)以及产气荚膜梭菌的细胞毒素。这些毒素与家畜的严重病理状况有关,包括气性坏疽(索氏梭菌和诺维氏梭菌)、传染性坏死性肝炎(诺维氏梭菌)、禽坏死性肠炎(产气荚膜梭菌)和小肠结肠炎(艰难梭菌)。免疫预防对于控制这些疾病至关重要,但传统疫苗面临生产挑战,如劳动密集型工艺,且往往免疫原性较低。这导致人们对重组疫苗的兴趣增加。虽然TcdA和TcdB在人类免疫方面已有充分研究,但其他LCTs的特征仍了解不足,需要进一步研究。因此,本研究强调了了解研究较少的毒素的重要性,并提出使用免疫信息学来识别它们的免疫显性区域。通过使用计算机工具绘制这些区域,并考虑它们与TcdA和TcdB的同源性,该研究旨在指导未来兽医疫苗学的研究。它还探索了克服传统疫苗和重组疫苗局限性的替代方法,为制定更有效的动物严重感染疫苗接种策略提供了指导方针。

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