志贺氏菌是一种主要的全球性病原体,是志贺氏菌病的病原,主要影响低收入和中等收入国家的腹泻病。志贺氏菌病的特点是复杂的,多步骤的发病过程中,细菌使用多种入侵蛋白来操纵和入侵肠上皮。抗体,特别是针对O-抗原和一些入侵蛋白,发挥保护作用,因为针对特定抗原的滴度与疾病严重程度成反比;然而,发病机理中抗体作用的背景还有待阐明,特别是志贺氏菌主要是细胞内病原体。在没有相关保护的情况下,功能测定重建志贺氏菌发病机制的重要时刻可以提高我们对保护性抗体在阻断感染和疾病中的作用的理解。体外测定是建立保护相关性的重要工具。只是最近的动物模型来概括人类的发病机制,往往不完整,已经建立。这篇综述旨在讨论体外试验,以根据多步多面志贺氏菌感染过程评估抗志贺氏菌抗体在多克隆血清中的功能。的确,单独测量抗体水平可能会限制对完整疫苗潜力的评估。血清杀菌试验(SBA),和其他功能测定,如调理吞噬杀伤测定(OPKA),和粘附/侵袭抑制试验(AIA),相反,它们具有生理相关性,并且可能提供有关这些效应子机制在保护性免疫中所起作用的重要信息。最终,这篇综述旨在为该领域的科学家提供新的观点,以了解所选择的功能测定的重要性,这些方法可能更代表免疫介导的保护机制。
Shigella is a major global pathogen and the etiological agent of shigellosis, a diarrheal disease that primarily affects low- and middle-income countries. Shigellosis is characterized by a complex, multistep pathogenesis during which bacteria use multiple invasion proteins to manipulate and invade the intestinal epithelium. Antibodies, especially against the O-antigen and some invasion proteins, play a protective role as titres against specific antigens inversely correlate with disease severity; however, the context of antibody action during pathogenesis remains to be elucidated, especially with Shigella being mostly an intracellular pathogen. In the absence of a correlate of protection, functional assays rebuilding salient moments of Shigella pathogenesis can improve our understanding of the role of protective antibodies in blocking infection and disease. In vitro assays are important tools to build correlates of protection. Only recently animal models to recapitulate human pathogenesis, often not in full, have been established. This
review aims to discuss in vitro assays to evaluate the functionality of anti-Shigella antibodies in polyclonal sera in light of the multistep and multifaced Shigella infection process. Indeed, measurement of antibody level alone may limit the evaluation of full vaccine potential. Serum bactericidal assay (SBA), and other functional assays such as opsonophagocytic killing assays (OPKA), and adhesion/invasion inhibition assays (AIA), are instead physiologically relevant and may provide important information regarding the role played by these effector mechanisms in protective immunity. Ultimately, the
review aims at providing scientists in the field with new points of view regarding the significance of functional assays of choice which may be more representative of immune-mediated protection mechanisms.