Sun Min, Liu Yu, Ni Xiumei, Tan Runqing, Wang Yi, Jiang Yajun, Ke Dingxin, Du Han, Guo Gang, Liu Kaiyun
Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China.
Biopharmaceutical Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China.
Microbes Infect. 2025 Mar-Apr;27(3):105433. doi: 10.1016/j.micinf.2024.105433. Epub 2024 Oct 24.
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.
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的理想策略。Toll样受体（TLR）配体已显示出作为诱导免疫反应的疫苗佐剂的潜力，但聚肌苷酸-聚胞苷酸（poly I:C），一种基于核酸的TLR9配体，在幽门螺杆菌疫苗研究中的研究较少。在这里，我们评估了聚肌苷酸-聚胞苷酸（poly 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联合使用以预防幽门螺杆菌感染的效果。为了分析特异性免疫反应，在免疫小鼠中测量了特异性抗体水平和脾脏细胞因子水平。与CpG ODN相比，聚肌苷酸-聚胞苷酸（poly I:C）可诱导黏膜sIgA抗体反应并减少幽门螺杆菌定植。此外，聚肌苷酸-聚胞苷酸（poly I:C）和CpG ODN的组合产生了更强的免疫保护作用，并显著减轻了胃炎，发挥了协同作用。脾脏细胞因子分析表明，聚肌苷酸-聚胞苷酸（poly I:C）主要引发混合的Th1/Th2/Th17免疫反应，而CpG ODN和聚肌苷酸-聚胞苷酸（poly I:C）的组合诱导了Th1/Th17免疫反应。我们的研究结果表明，黏膜sIgA抗体水平的升高和强大的脾脏Th1/Th17免疫反应与接种疫苗小鼠中幽门螺杆菌定植的减少有关。这项研究确定了一种潜在的TLR配体佐剂，可用于开发更有效的幽门螺杆菌疫苗。
