Intranasal immunization with poly I:C and CpG ODN adjuvants enhances the protective efficacy against Helicobacter pylori infection in mice.

IF 2.6 4区 医学 Q3 IMMUNOLOGY Microbes and Infection Pub Date : 2024-10-24 DOI:10.1016/j.micinf.2024.105433
Min Sun, Yu Liu, Xiumei Ni, Runqing Tan, Yi Wang, Yajun Jiang, Dingxin Ke, Han Du, Gang Guo, Kaiyun Liu
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Abstract

Helicobacter pylori (H. pylori) infection is a serious public health issue, and development of vaccines is a desirable preventive strategy for H. pylori. Toll-like receptor (TLR) ligands have shown potential as vaccine adjuvants that induce immune responses, but polyinosinic-polycytidylic acid (poly I:C), a nucleic acid-based TLR9 ligand, is less well studied in H. pylori vaccine research. Here, we evaluated the effects of poly I:C and CpG oligodeoxynucleotide (CpG ODN), a nucleic acid TLR3 ligand, as adjuvants in combination with the H. pylori recombinant proteins LpoB and UreA to protect against H. pylori infection. For analysis of specific immune responses, the levels of specific antibodies and splenic cytokines were measured in the immunized mice. Compared with CpG ODN, poly I:C could induce mucosal sIgA antibody responses and reduce H. pylori colonization. Additionally, the combination of poly I:C and CpG ODN caused greater immunoprotection and significantly reduced gastritis, exerting synergistic effects. Analysis of splenic cytokines revealed that poly I:C mainly triggered a mixed Th1/Th2/Th17 immune response, whereas the combination of CpG ODN and poly I:C induced a Th1/Th17 immune response. Our findings indicated that increased levels of mucosal sIgA antibodies and a robust splenic Th1/Th17 immune response were associated with reduced H. pylori colonization in vaccinated mice. This study identified a potential TLR ligand adjuvant for developing more effective H. pylori vaccines.

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使用聚 I:C 和 CpG ODN 佐剂进行鼻内免疫可增强小鼠对幽门螺旋杆菌感染的保护效力。
幽门螺杆菌(H. pylori)感染是一个严重的公共卫生问题,开发疫苗是预防幽门螺杆菌感染的理想策略。Toll样受体(TLR)配体已显示出作为疫苗佐剂诱导免疫反应的潜力,但聚肌苷酸-聚胞苷酸(poly I:C)这种基于核酸的TLR9配体在幽门螺杆菌疫苗研究中的研究较少。在这里,我们评估了聚 I:C 和核酸 TLR3 配体 CpG 寡脱氧核苷酸(CpG ODN)作为佐剂与幽门螺杆菌重组蛋白 LpoB 和 UreA 结合使用对预防幽门螺杆菌感染的效果。为了分析特异性免疫反应,测量了免疫小鼠体内特异性抗体和脾细胞因子的水平。与 CpG ODN 相比,多聚 I:C 可诱导粘膜 sIgA 抗体反应,减少幽门螺杆菌定植。此外,多聚 I:C 和 CpG ODN 的组合能产生更强的免疫保护作用,并能显著减轻胃炎,发挥协同效应。对脾脏细胞因子的分析表明,多聚 I:C 主要引发 Th1/Th2/Th17 混合免疫反应,而 CpG ODN 和多聚 I:C 的组合则诱导 Th1/Th17 免疫反应。我们的研究结果表明,粘膜 sIgA 抗体水平的提高和脾脏 Th1/Th17 免疫反应的增强与接种疫苗的小鼠幽门螺杆菌定植率的降低有关。这项研究为开发更有效的幽门螺杆菌疫苗找到了一种潜在的 TLR 配体佐剂。
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来源期刊
Microbes and Infection
Microbes and Infection 医学-病毒学
CiteScore
12.60
自引率
1.70%
发文量
90
审稿时长
40 days
期刊介绍: Microbes and Infection publishes 10 peer-reviewed issues per year in all fields of infection and immunity, covering the different levels of host-microbe interactions, and in particular: the molecular biology and cell biology of the crosstalk between hosts (human and model organisms) and microbes (viruses, bacteria, parasites and fungi), including molecular virulence and evasion mechanisms. the immune response to infection, including pathogenesis and host susceptibility. emerging human infectious diseases. systems immunology. molecular epidemiology/genetics of host pathogen interactions. microbiota and host "interactions". vaccine development, including novel strategies and adjuvants. Clinical studies, accounts of clinical trials and biomarker studies in infectious diseases are within the scope of the journal. Microbes and Infection publishes articles on human pathogens or pathogens of model systems. However, articles on other microbes can be published if they contribute to our understanding of basic mechanisms of host-pathogen interactions. Purely descriptive and preliminary studies are discouraged.
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