鼻内给予的CpG-寡脱氧核苷酸是抗幽门螺杆菌疫苗的一种有效佐剂，且1型辅助性T细胞应答和γ干扰素与这种保护作用相关。

Intranasal CpG-oligodeoxynucleotide is a potent adjuvant of vaccine against Helicobacter pylori, and T helper 1 type response and interferon-gamma correlate with the protection.

作者信息

Shi Tong, Liu Wen-zhong, Gao Fei, Shi Gui-ying, Xiao Shu-dong

机构信息

Ren Ji Hospital, Shanghai Institute of Digestive Disease, Shanghai Second Medical University, Shanghai, China 20001.

出版信息

Helicobacter. 2005 Feb;10(1):71-9. doi: 10.1111/j.1523-5378.2005.00293.x.

DOI:10.1111/j.1523-5378.2005.00293.x

PMID:15691317

Abstract

BACKGROUND

Although a series of vaccines against Helicobacter pylori have emerged in the past 10 years, the mechanism involved in their protective effect is yet to be elucidated, and more effective vaccine adjuvants remain to be developed. In this study, CpG-oligodeoxynucleotide (CpG-ODN) was investigated as a new candidate for a H. pylori vaccine adjuvant. Furthermore, the role of T helper 1 (Th1) type response and interferon (IFN)-gamma in the protective immunity was explored.

METHODS

C57BL/6 mice and IFN-gamma knockout mice were intranasally or orally immunized with H. pylori whole cell sonicate (WCS)/CpG-ODN and challenged with different doses [5 x 10(8) and 5 x 10(6) colony-forming units (CFU)] of H. pylori. The protective effect was assessed as the percentage of noninfected mice. The responsive antibodies and cytokines were analyzed using an enzyme-linked immunosorbent assay (ELISA) and flow cytometry.

RESULTS

The prevention rates against H. pylori infection in mice intranasally immunized with WCS plus CpG-ODN were dramatically higher than those in sham-immunized mice (70% vs. 0%, challenged with 5 x 10(8) CFU H. pylori; 90% vs. 20%, challenged with 5 x 10(6) CFU H. pylori). Significantly higher levels of immunoglobulin G2a (IgG2a) and IFN-gamma were detected in the mice immunized with WCS/CpG than in sham-immunized controls. However, vaccination failed to effectively protect IFN-gamma knockout mice challenged with H. pylori.

CONCLUSIONS

CpG-ODN given intranasally is a potent adjuvant for development of a H. pylori vaccine. Th1-type response and IFN-gamma are involved in the protection.

摘要

背景

尽管在过去10年中出现了一系列抗幽门螺杆菌疫苗，但它们的保护作用机制仍有待阐明，且更有效的疫苗佐剂仍有待开发。在本研究中，对CpG-寡脱氧核苷酸（CpG-ODN）作为幽门螺杆菌疫苗佐剂的新候选物进行了研究。此外，还探讨了辅助性T细胞1（Th1）型反应和干扰素（IFN）-γ在保护性免疫中的作用。

方法

将C57BL/6小鼠和IFN-γ基因敲除小鼠用幽门螺杆菌全细胞超声裂解物（WCS）/CpG-ODN进行鼻内或口服免疫，并用不同剂量[5×10⁸和5×10⁶菌落形成单位（CFU）]的幽门螺杆菌进行攻击。以未感染小鼠的百分比评估保护效果。使用酶联免疫吸附测定（ELISA）和流式细胞术分析反应性抗体和细胞因子。

结果

用WCS加CpG-ODN鼻内免疫的小鼠对幽门螺杆菌感染的预防率显著高于假免疫小鼠（用5×10⁸CFU幽门螺杆菌攻击时为70%对0%；用5×10⁶CFU幽门螺杆菌攻击时为90%对20%）。在用WCS/CpG免疫的小鼠中检测到的免疫球蛋白G2a（IgG2a）和IFN-γ水平明显高于假免疫对照组。然而，疫苗接种未能有效保护受到幽门螺杆菌攻击的IFN-γ基因敲除小鼠。