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首页> 外文期刊>Vaccine >Differential regulation of polysaccharide-specific antibody responses to isolated polysaccharides, conjugate vaccines, and intact Gram-positive versus Gram-negative extracellular bacteria
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Differential regulation of polysaccharide-specific antibody responses to isolated polysaccharides, conjugate vaccines, and intact Gram-positive versus Gram-negative extracellular bacteria

机译：对分离的多糖，结合疫苗以及完整革兰氏阳性和革兰氏阴性细胞外细菌的多糖特异性抗体反应的差异调节

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Bacterial capsular polysaccharides are major virulence factors and are key targets in a number of licensed anti-bacterial vaccines. Their major characteristics are their large molecular weight and expression of repeating antigenic epitopes that mediate multivalent B cell receptor cross-linking. In addition, since the majority of these antigens cannot associate with MHC-II they fail to recruit CD4+ T cell help and are referred to as T cell-independent antigens. In this review I will discuss a series of studies from my laboratory that have underscored the importance of understanding polysaccharide-specific antibody responses within the context in which the PS is expressed (i.e. in isolation, as a component of conjugate vaccines, and expressed naturally by intact bacteria). We have shown that multivalent B cell receptor crosslinking, as mediated by polysaccharides, uniquely determines the qualitative response of the B cell to subsequent stimuli, but by itself is insufficient to induce antibody secretion or class switching. For these latter events to occur, second signals must act in concert with primary signals derived from the B cell receptor. The co-expression of polysaccharide and protein within intact bacteria promotes recruitment of CD4+ T cell help for the associated PS-specific IgG response, in contrast to isolated polysaccharides. Further, the particulate nature of extracellular bacteria confers properties to the polysaccharide-specific IgG response that makes it distinct immunologically from soluble conjugate vaccines. Finally, the underlying biochemical and/or structural differences that distinguish Gram-positive and Gram-negative bacteria appear to play critical roles in differentially regulating the associated polysaccharide-specific IgG responses to these groups of pathogens. These studies have a number of implications for the understanding and future design of polysaccharide-based vaccines. Published by Elsevier Ltd.
机译：细菌荚膜多糖是主要的毒力因子，并且是许多获得许可的抗菌疫苗的主要靶标。它们的主要特征是它们的大分子量和介导多价B细胞受体交联的重复抗原表位的表达。另外，由于这些抗原中的大多数不能与MHC-II结合，因此它们无法募集CD4 + T细胞的帮助，因此被称为非T细胞抗原。在这篇综述中，我将讨论来自我实验室的一系列研究，这些研究强调了在PS表达的背景下（即，作为结合疫苗的一种成分分离并通过以下方式自然表达）了解多糖特异性抗体反应的重要性。完整的细菌）。我们已经表明，由多糖介导的多价B细胞受体交联可唯一确定B细胞对随后刺激的定性反应，但其本身不足以诱导抗体分泌或类别转换。为了使这些后面的事件发生，第二信号必须与源自B细胞受体的第一信号协同作用。与分离的多糖相比，完整细菌内多糖和蛋白质的共表达促进CD4 + T细胞的募集，从而有助于相关的PS特异性IgG反应。此外，细胞外细菌的颗粒性质赋予多糖特异性IgG应答以特性，这使其在免疫学上不同于可溶性结合疫苗。最后，区分革兰氏阳性和革兰氏阴性细菌的潜在生化和/或结构差异似乎在差异性调节对这些病原体的相关多糖特异性IgG反应中起关键作用。这些研究对于基于多糖的疫苗的理解和未来设计具有许多意义。由Elsevier Ltd.发布

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