Del Tordello Elena, Danilchanka Olga, McCluskey Andrew J, Mekalanos John J
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115.
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115
Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3042-7. doi: 10.1073/pnas.1524290113. Epub 2016 Feb 29.
The bacterial type 6 secretion system (T6SS) is a dynamic apparatus that translocates proteins between cells by a mechanism analogous to phage tail contraction. T6SS sheaths are cytoplasmic tubular structures composed of stable VipA-VipB (named for ClpV-interacting protein A and B) heterodimers. Here, the structure of the VipA/B sheath was exploited to generate immunogenic multivalent particles for vaccine delivery. Sheaths composed of VipB and VipA fused to an antigen of interest were purified from Vibrio cholerae or Escherichia coli and used for immunization. Sheaths displaying heterologous antigens generated better immune responses against the antigen and different IgG subclasses compared with soluble antigen alone. Moreover, antigen-specific antibodies raised against sheaths presenting Neisseria meningitidis factor H binding protein (fHbp) antigen were functional in a serum bactericidal assay. Our results demonstrate that multivalent nanoparticles based on the T6SS sheath represent a versatile scaffold for vaccine applications.
细菌VI型分泌系统（T6SS）是一种动态装置，通过类似于噬菌体尾部收缩的机制在细胞间转运蛋白质。T6SS鞘是由稳定的VipA-VipB（因其与ClpV相互作用蛋白A和B而得名）异二聚体组成的细胞质管状结构。在此，利用VipA/B鞘的结构生成用于疫苗递送的免疫原性多价颗粒。将与感兴趣的抗原融合的VipB和VipA组成的鞘从霍乱弧菌或大肠杆菌中纯化出来并用于免疫。与单独的可溶性抗原相比，展示异源抗原的鞘产生了针对该抗原和不同IgG亚类的更好免疫反应。此外，针对呈现脑膜炎奈瑟菌因子H结合蛋白（fHbp）抗原的鞘产生的抗原特异性抗体在血清杀菌试验中具有功能。我们的结果表明，基于T6SS鞘的多价纳米颗粒代表了一种用于疫苗应用的通用支架。
