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针对四种毒力因子的重组乳杆菌疫苗 LL-plSAM-WAE 可提供针对 H. pylori 感染的黏膜免疫。

Recombinant L. lactis vaccine LL-plSAM-WAE targeting four virulence factors provides mucosal immunity against H. pylori infection.

机构信息

College of First Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, China.

College of Laboratory Medicine , Ningxia Medical University, Yinchuan, 750004, China.

出版信息

Microb Cell Fact. 2024 Feb 24;23(1):61. doi: 10.1186/s12934-024-02321-4.

Abstract

BACKGROUND

Helicobacter pylori (H. pylori) causes chronic gastric disease. An efficient oral vaccine would be mucosa-targeted and offer defense against colonization of invasive infection in the digestive system. Proteolytic enzymes and acidic environment in the gastrointestinal tract (GT) can, however, reduce the effectiveness of oral vaccinations. For the creation of an edible vaccine, L. lactis has been proposed as a means of delivering vaccine antigens.

RESULTS

We developed a plSAM (pNZ8148-SAM) that expresses a multiepitope vaccine antigen SAM-WAE containing Urease, HpaA, HSP60, and NAP extracellularly (named LL-plSAM-WAE) to increase the efficacy of oral vaccinations. We then investigated the immunogenicity of LL-plSAM-WAE in Balb/c mice. Mice that received LL-plSAM-WAE or SAM-WAE with adjuvant showed increased levels of antibodies against H. pylori, including IgG and sIgA, and resulted in significant reductions in H. pylori colonization. Furthermore, we show that SAM-WAE and LL-plSAM-WAE improved the capacity to target the vaccine to M cells.

CONCLUSIONS

These findings suggest that recombinant L. lactis could be a promising oral mucosa vaccination for preventing H. pylori infection.

摘要

背景

幽门螺杆菌(H. pylori)会导致慢性胃病。一种有效的口服疫苗应该是黏膜靶向的,并能提供针对消化系统侵袭性感染的防御。然而,胃肠道(GT)中的蛋白水解酶和酸性环境会降低口服疫苗的效果。为了开发可食用疫苗,已提议使用乳球菌(L. lactis)作为传递疫苗抗原的手段。

结果

我们开发了一种 plSAM(pNZ8148-SAM),它在外分泌表达多表位疫苗抗原 SAM-WAE,其中包含脲酶、HpaA、HSP60 和 NAP(命名为 LL-plSAM-WAE),以提高口服疫苗的效果。然后,我们在 Balb/c 小鼠中研究了 LL-plSAM-WAE 的免疫原性。接受 LL-plSAM-WAE 或 SAM-WAE 佐剂的小鼠显示出针对 H. pylori 的抗体水平升高,包括 IgG 和 sIgA,并显著降低了 H. pylori 的定植。此外,我们表明 SAM-WAE 和 LL-plSAM-WAE 提高了疫苗靶向 M 细胞的能力。

结论

这些发现表明,重组乳球菌可能是一种有前途的预防 H. pylori 感染的口服黏膜疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ea1/10893618/aa4c44372572/12934_2024_2321_Fig1_HTML.jpg

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