GSK Vaccines Institute for Global Health (GVGH) S.r.l., Siena, Italy.
Department of Life Sciences, Imperial College London, London, United Kingdom.
Front Cell Infect Microbiol. 2023 May 16;13:1171213. doi: 10.3389/fcimb.2023.1171213. eCollection 2023.
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 being mostly an intracellular pathogen. In the absence of a correlate of protection, functional assays rebuilding salient moments of pathogenesis can improve our understanding of the role of protective antibodies in blocking infection and disease. 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 assays to evaluate the functionality of anti- antibodies in polyclonal sera in light of the multistep and multifaced 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.
志贺氏菌是一种主要的全球病原体，也是志贺菌病的病原体，志贺菌病是一种腹泻病，主要影响中低收入国家。志贺菌病的发病机制复杂，多步骤，在此过程中，细菌利用多种侵袭蛋白来操纵和侵袭肠上皮细胞。抗体，特别是针对 O 抗原和一些侵袭蛋白的抗体，发挥保护作用，因为针对特定抗原的抗体效价与疾病严重程度呈反比；然而，在发病机制中抗体作用的背景仍有待阐明，特别是因为志贺氏菌主要是一种细胞内病原体。在缺乏保护相关物的情况下，重建发病机制重要时刻的功能测定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。 测定是构建保护相关物的重要工具。只有最近才建立了能够重现人类发病机制的动物模型，但通常并不完整。本文旨在讨论 测定，以根据多步骤和多方面的 感染过程评估多克隆血清中抗-抗体的功能。事实上，仅测量抗体水平可能会限制对疫苗全部潜力的评估。血清杀菌测定（SBA）和其他功能测定，如调理吞噬杀伤测定（OPKA）和黏附/入侵抑制测定（AIA），则具有生理相关性，并可能提供关于这些效应机制在保护性免疫中所起作用的重要信息。最终，本文旨在为该领域的科学家提供新的观点，即选择的功能测定更能代表免疫介导的保护机制的重要性。
