鼠型衣原体 T 细胞抗原与佐剂 DDA/TDB 联合使用可诱导针对感染的免疫反应，与高频率的γ干扰素（IFN-γ）/肿瘤坏死因子α和 IFN-γ/白细胞介素-17 双阳性 CD4+T 细胞相关。

Chlamydia muridarum T-cell antigens formulated with the adjuvant DDA/TDB induce immunity against infection that correlates with a high frequency of gamma interferon (IFN-gamma)/tumor necrosis factor alpha and IFN-gamma/interleukin-17 double-positive CD4+ T cells.

机构信息

British Columbia Centre for Disease Control, Vancouver, BC, Canada.

出版信息

Infect Immun. 2010 May;78(5):2272-82. doi: 10.1128/IAI.01374-09. Epub 2010 Mar 15.

DOI:10.1128/IAI.01374-09

PMID:20231405

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2863536/

Abstract

Major impediments to developing a Chlamydia vaccine lie in identifying immunologically relevant T-cell antigens and delivery in a manner to stimulate protective immunity. Using an immunoproteomic approach, we previously identified three immunodominant Chlamydia T-cell antigens (PmpG-1, PmpE/F-2, and RplF). Because RplF has high homology to a human ortholog, it may not be suitable for human vaccine development. Therefore, in this study, we evaluated protection against Chlamydia infection in the genital tract in C57BL/6 mice immunized with Chlamydia-specific membrane proteins PmpG-1, PmpE/F-2, and major outer membrane protein (MOMP; as a reference) or a combination of them formulated with one of three adjuvants, CpG oligodeoxynucleotide (CpG-ODN), AbISCO-100 (AbISCO), or DDA/TDB (dimethyldioctadecylammonium bromide/D-(+)-trehalose 6,6'-dibehenate). The results show that immunization with the CpG-ODN formulation failed to provide protection against Chlamydia infection; the AbISCO formulation conferred moderate protection, and the DDA/TDB formulation showed the highest degree of protective efficacy. The combination of PmpG-1, PmpE/F-2, and MOMP proteins formulated with DDA/TDB exhibited the greatest degree of protection among all vaccine groups studied. Moreover, this vaccine combination also engendered significant protection in BALB/c mice, which have a different major histocompatibility complex (MHC) background. We measured cell-mediated immune cytokine responses in mice immunized with PmpG-1 mixed with each of the three adjuvants. The results demonstrate that mice immunized with the DDA/TDB formulation induced the strongest gamma interferon (IFN-gamma) and interleukin-17 (IL-17) responses, characterized by the highest frequency of IFN-gamma/tumor necrosis factor alpha (TNF-alpha) and IFN-gamma/IL-17 double-positive CD4(+) T cells. In conclusion, a Chlamydia vaccine based on the recombinant proteins PmpG-1, PmpE/F-2, and MOMP delivered in a DDA/TDB adjuvant conferred protection against infection that correlated with IFN-gamma/TNF-alpha and IFN-gamma/IL-17 double-positive CD4(+) T cells.

摘要

开发衣原体疫苗的主要障碍在于确定具有免疫相关性的 T 细胞抗原，并以刺激保护性免疫的方式进行递送。我们之前使用免疫蛋白质组学方法鉴定了三种免疫显性衣原体 T 细胞抗原（PmpG-1、PmpE/F-2 和 RplF）。由于 RplF 与人同源物具有高度同源性，因此它可能不适合用于人类疫苗开发。因此，在这项研究中，我们评估了用衣原体特异性膜蛋白 PmpG-1、PmpE/F-2 和主要外膜蛋白（MOMP 作为参考）或它们的组合免疫接种 C57BL/6 小鼠对生殖道衣原体感染的保护作用，这些蛋白与三种佐剂中的一种（CpG 寡脱氧核苷酸（CpG-ODN）、AbISCO-100（AbISCO）或 DDA/TDB（二甲基十八烷基溴化铵/（+）-海藻糖 6,6'-二硬脂酸酯）进行了配制。结果表明，CpG-ODN 制剂的免疫接种未能提供针对衣原体感染的保护；AbISCO 制剂提供了适度的保护，而 DDA/TDB 制剂显示出最高程度的保护效果。用 DDA/TDB 配制的 PmpG-1、PmpE/F-2 和 MOMP 蛋白的组合在所有研究的疫苗组中显示出最大程度的保护。此外，这种疫苗组合在具有不同主要组织相容性复合物（MHC）背景的 BALB/c 小鼠中也产生了显著的保护作用。我们测量了用 PmpG-1 与三种佐剂中的每一种混合免疫的小鼠的细胞介导的免疫细胞因子反应。结果表明，用 DDA/TDB 制剂免疫的小鼠诱导了最强的干扰素γ（IFN-γ）和白细胞介素-17（IL-17）反应，其特征是 IFN-γ/肿瘤坏死因子-α（TNF-α）和 IFN-γ/IL-17 双阳性 CD4+T 细胞的频率最高。总之，基于重组蛋白 PmpG-1、PmpE/F-2 和 MOMP 的衣原体疫苗，用 DDA/TDB 佐剂递送，可提供针对感染的保护，这与 IFN-γ/TNF-α 和 IFN-γ/IL-17 双阳性 CD4+T 细胞相关。