Wang Zhu, Lazinski David W, Camilli Andrew
Department of Molecular Biology and Microbiology, Tufts University School of Medicine and Howard Hughes Medical Institute, Boston, Massachusetts, USA.
Department of Molecular Biology and Microbiology, Tufts University School of Medicine and Howard Hughes Medical Institute, Boston, Massachusetts, USA
Infect Immun. 2016 Dec 29;85(1). doi: 10.1128/IAI.00626-16. Print 2017 Jan.
An outer membrane vesicle (OMV)-based cholera vaccine is highly efficacious in preventing intestinal colonization in the suckling mouse model. Immunity from OMVs comes from immunoglobulin (Ig), particularly IgG, in the milk of mucosally immunized dams. Anti-OMV IgG renders Vibrio cholerae organisms immotile, thus they pass through the small intestine without colonizing. However, the importance of motility inhibition for protection and the mechanism by which motility is inhibited remain unclear. By using both in vitro and in vivo experiments, we found that IgG inhibits motility by specifically binding to the O-antigen of V. cholerae We demonstrate that the bivalent structure of IgG, although not required for binding to the O-antigen, is required for motility inhibition. Finally, we show using competition assays in suckling mice that inhibition of motility appears to be responsible for most, if not all, of the protection engendered by OMV vaccination, thus providing insight into the mechanism of immune protection.
基于外膜囊泡（OMV）的霍乱疫苗在预防乳鼠模型中的肠道定植方面具有很高的效力。来自OMV的免疫来自于经黏膜免疫的母鼠乳汁中的免疫球蛋白（Ig），尤其是IgG。抗OMV IgG使霍乱弧菌失去运动能力，因此它们能穿过小肠而不发生定植。然而，运动抑制对保护作用的重要性以及运动被抑制的机制仍不清楚。通过体外和体内实验，我们发现IgG通过特异性结合霍乱弧菌的O抗原抑制运动。我们证明，IgG的二价结构虽然不是与O抗原结合所必需的，但却是运动抑制所必需的。最后，我们在乳鼠中使用竞争试验表明，运动抑制似乎对OMV疫苗接种产生的大部分（如果不是全部）保护作用负责，从而为免疫保护机制提供了见解。
