Promoting Immune Efficacy of the Oral Helicobacter pylori Vaccine by HP55/PBCA Nanoparticles against the Gastrointestinal Environment
Promoting Immune Efficacy of the Oral Helicobacter pylori Vaccine by HP55/PBCA Nanoparticles against the Gastrointestinal Environment
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HP55/PBCA纳米颗粒提高口服幽门螺杆菌疫苗对胃肠道环境的免疫功效
DOI：
10.1021/acs.molpharmaceut.8b00251
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发表时间：
2018
影响因子：
4.9
通讯作者：
Xing Yingying
中科院分区：
文献类型：
--
作者：
Hai Liu;Wei Liu;Zhoulin Tan;Zhiqin Zeng;Huimin Yang;Shuanghui Luo;Linlin Wang;Xi Tao;Xing Yingying
口服亚单位疫苗的免疫原性较差，部分原因是由于胃肠道的恶劣环境。对于一些局限于胃肠道的病原体，就地接种的疫苗可能比非肠道接种的疫苗提供更有效的保护。然而，目前还没有合适的口服亚单位疫苗递送系统。在本研究中，我们设计了HP55/聚氰丙烯酸正丁基酯（PBCA）纳米颗粒（NPs）来携带幽门螺杆菌(H。预防小鼠模型口服幽门螺杆菌亚单位疫苗CCF。这些NPs是用界面聚合方法合成的，它们不仅可以保护CCF抗原免受模拟胃液（SGF, pH 1.2）的酸性pH，也可以保护CCF抗原免受模拟肠液（SIF, pH 7.4）的蛋白质水解。小鼠口服接种HP55/PBCA-CCF NPs可促进血清抗原特异性抗体、黏膜分泌IgA和促炎细胞因子的产生。此外，在HP55/PBCA-CCF np免疫小鼠的胃组织中发现Th1/Th17反应和淋巴细胞增加，这可能最终限制了ith。pyloricolonization。总之，这些结果表明，HP55/PBCA NPs是对抗胃肠道严重情况的有希望的载体，因此可以进一步用于其他口服疫苗或药物。
The immunogenicity of oral subunit vaccines is poor partly as a result of the harsh milieu of the gastrointestinal (GI) tract. For some pathogens that restrictedly inhabit the GI tract, a vaccine that works in situ may provide more potent protection than vaccines that operate parenterally. Yet, no appropriate delivery system is available for oral subunit vaccines. In this study, we designed HP55/poly(n-butylcyanoacrylate) (PBCA) nanoparticles (NPs) to carryHelicobacter pylori(H. pylori) subunit vaccine CCF for oral administration in a prophylactic mice model. These NPs, which are synthesized using an interfacial polymerization method, protected the CCF antigen not only from the acidic pH in simulated gastric fluid (SGF, pH 1.2) but also from the proteolysis in simulated intestinal fluid (SIF, pH 7.4). Oral vaccination of mice with HP55/PBCA-CCF NPs promoted the production of serum antigen-specific antibodies, mucosal secretory IgA, and proinflammatory cytokines. Moreover, a Th1/Th17 response and augmented lymphocytes were found in the gastric tissue of HP55/PBCA-CCF NP-immunized mice, which might eventually limitH. pyloricolonization. Collectively, these results indicate that HP55/PBCA NPs are promising carriers against the severe situation of the GI tract and thereby may be further utilized for other orally administrated vaccines or drugs.