Recombinant Bacillus subtilis spores expressing cholera toxin B subunit and Helicobacter pylori urease B confer protection against H. pylori in mice

• Published in: Journal of medical microbiology Vol. 66; no. 1; pp. 83 - 89
• Main Authors: Zhou, Zhenwen, Dong, Hui, Huang, Yanmei, Yao, Shuwen, Liang, Bingshao, Xie, Yongqiang, Long, Yan, Mai, Jialiang, Gong, Sitang
• Format: Journal Article
• Language: English
• Published: England 01.01.2017
• Subjects: Animals; Antibodies, Bacterial - immunology; Bacillus subtilis - immunology; Bacterial Load; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacterial Vaccines - immunology; Cholera Toxin - genetics; Cholera Toxin - immunology; Cloning, Molecular; DNA, Bacterial - genetics; Female; Helicobacter Infections - immunology; Helicobacter Infections - prevention & control; Helicobacter pylori - enzymology; Helicobacter pylori - immunology; Immunoglobulin A - immunology; Immunoglobulin G - immunology; Interferon-gamma - immunology; Interleukin-10 - immunology; Mice; Mice, Inbred BALB C; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Spleen - cytology; Spleen - immunology; Spores, Bacterial - immunology; Urease - genetics; Urease - immunology
• ISSN: 0022-2615; 1473-5644
• DOI: 10.1099/jmm.0.000404

Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. The limitations of current therapies for H. pylori infection include poor compliance and antibiotic resistance. Therefore, an effective anti-H. pylori vaccine would be an alternative or complement to antibiotic treatment. Urease B (UreB) is considered an ideal vaccine antigen against H. pylori infection. In this study, cholera toxin B subunit (CTB), a mucosal adjuvant, was used to enhance the immunogenicity of a novel Bacillus subtilis spore vaccine expressing CTB-UreB, along with the B. subtilis spore coat protein CotC as a fusion protein. Oral administration of B. subtilis spores expressing CotC-UreB or CotC-CTB-UreB led to increased levels of UreB-specific IgG in serum and UreB-specific IgA in faeces, as well as elevated levels of IL-10 and IFN-γ in splenocytes. In addition, oral administration of CotC-UreB or CotC-CTB-UreB spores induced significant reductions (80.0 and 90.5 %, respectively) in gastric H. pylori bacterial load (1.11±0.36×105 and 0.53±0.21×105 c.f.u., respectively) compared to that of the CotC control group (5.56±1.64×105 c.f.u., P<0.01). Moreover, CotC-CTB-UreB spores were significantly more effective at reducing the bacterial load than CotC-UreB spores (P<0.05). These results indicate that CotC-CTB-UreB-expressing B. subtilis spores are a potential vaccine candidate for the control of H. pylori infection.