E. coli Enterotoxin LtB Enhances Vaccine-Induced Anti-H. pylori Protection by Promoting Leukocyte Migration into Gastric Mucus via Inflammatory Lesions

Peng, Xiaoyan; Zhang, Rongguang; Wang, Chen; Yu, Fengkuan; Yu, Ming‐Whei; Chen, Shuaiyin; Fan, Qi-Wen; Xi, Yang

doi:10.3390/cells8090982

Cited by 8 publications

(10 citation statements)

References 46 publications

(72 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 28 ] After H. pylori challenges, LAB vaccine provided sufficient protection to immunized mice that decrease the gastric H. pylori colonization and urease activity. [ 29,30 ]…”

Section: The Influence Of Administration Routes On Immune Responsesmentioning

confidence: 99%

Recombinant lactic acid bacteria as promising vectors for mucosal vaccination

Qiao

Zhong

et al. 2021

Exploration

View full text Add to dashboard Cite

Lactic acid bacteria (LAB), a diverse family of gram‐positive bacteria, has been proven effective in delivering varieties of therapeutic and prophylactic molecules such as antigens and cytokines. Featuring the properties of acid‐resistant, high uptake into Peyer's patches, and superior capacity for inducing secretory IgA antibodies, LAB have good potential to be used as vaccine vectors for mucosal vaccination. Mucosal immunization enables both mucosal and systemic immune responses, which are critical for resisting pathogens that invade the host through the mucosal surfaces. With the development of genetic engineering, LAB strains, primarily Lactococcus and Lactobacillus have been exploited to express a range of heterologous antigens. Numerous studies have demonstrated that LAB mucosal vaccines can stimulate all arms of the immune system to provide adequate protection against pathogen infections. Additionally, several LAB‐based human papillomavirus vaccines have entered the clinical trial studies, which suggest the great promise of LAB vaccines for new interventions in mucosal transport diseases. Herein, we will discuss the factors that influence the immunogenicity of LAB vaccines, including LAB strains, the location of antigens, and administration routes, and focus on the current strategies that have been reported for optimizing LAB vaccines.

show abstract

“…[ 28 ] After H. pylori challenges, LAB vaccine provided sufficient protection to immunized mice that decrease the gastric H. pylori colonization and urease activity. [ 29,30 ]…”

Section: The Influence Of Administration Routes On Immune Responsesmentioning

confidence: 99%

Recombinant lactic acid bacteria as promising vectors for mucosal vaccination

Qiao

Zhong

et al. 2021

Exploration

View full text Add to dashboard Cite

show abstract

“…At present, the exact protective immune mechanisms against H. pylori are still not very clear ( 23 ). The development of preventive and therapeutic H. pylori vaccines has obtained encouraging protection results in animal models ( 24 – 26 ), with some vaccines entering clinical studies ( 27 – 29 ). However, most candidate vaccines are still in the early stages of development, and there are still difficulties and challenges in the development of safe and effective H. pylori vaccines.…”

Section: Discussionmentioning

confidence: 99%

Oral Administration of a Shigella 2aT32-Based Vaccine Expressing UreB-HspA Fusion Antigen With and Without Parenteral rUreB-HspA Boost Confers Protection Against Helicobacter pylori in Mice Model

et al. 2022

View full text Add to dashboard Cite

Helicobacter pylori (H. pylori) is a gram-negative pathogen classified as a class I carcinogen. The H. pylori urease B subunit (UreB) and heat shock protein A (HspA) are two important vaccine candidate antigens. In this study, we evaluated the immunogenicity and immunoprotective effect of the attenuated Shigella vector vaccine SH02 expressing the UreB-HspA fusion protein of H. pylori in a mouse model. Oral SH02 with or without subcutaneous injection of rUreB-HspA induced antigen-specific serum IgG, mucosal sIgA, and T cells immune response. Subcutaneous injection of the candidate antigen rUreB-HspA enhanced the level of serum antigen-specific IgG antibodies (p < 0.0001) and the levels of IgG1/IgG2a/IgG2b subtypes. In addition, injection boost also increased the proportion of spleen antigen-specific CD4+CD154+ T cells (p < 0.001), and the proportion of CD4+CD154+ T cells that secrete IFN-γ and IL-17A. Following the H. pylori challenge, the levels of H. pylori colonization in the two experimental groups (Groups A and B) significantly reduced compared with the control group (p < 0.001), indicating that the candidate vaccine yielded a preventive effect of anti-H.pylori infection. Compared with the non-subcutaneous booster injection group (Group A), the subcutaneous booster injection group (Group B) exhibited less gastric inflammation, but there was no significant difference in the level of colonization (p > 0.05). These results lay a foundation for the development of a vaccine against H. pylori and the optimization of immunization methods and procedures to prevent H. pylori infection.

show abstract

“…It is remarkable that the first use of oral vaccination against H. pylori infection is investigated by Czinn and Nedrud 53 . In most cases, CTB or LTB can serve as a strong mucosal adjuvant and promote the induction of protective immunity against H. pylori 43,44 . However, the adverse effects of these adjuvants in clinical trials, including diarrhea, low‐grade fever, and vomiting, 9,54 limit their further application.…”

Section: Discussionmentioning

confidence: 99%

“…Of note, adjuvanted H. pylori vaccines can induce significant immune protection against H. pylori infection 35–42 . Expression of fusions with Escherichia coli heat‐liable enterotoxin subunit B (LTB) or cholera toxin subunit B (CTB) has great potential to induce effective and comprehensive protection against H. pylori infection in a mouse model 43,44 . Although LTB and CTB are effective mucosal adjuvants, they do not have clinical approval and might cause diarrhea in a large proportion of volunteers 9,13 .…”

Section: Introductionmentioning

confidence: 99%

“…[35][36][37][38][39][40][41][42] Expression of fusions with Escherichia coli heat-liable enterotoxin subunit B (LTB) or cholera toxin subunit B (CTB) has great potential to induce effective and comprehensive protection against H. pylori infection in a mouse model. 43,44 Although LTB and CTB are effective mucosal adjuvants, they do not have clinical approval and might cause diarrhea in a large proportion of volunteers. 9,13 Furthermore, oral vaccines containing live attenuated Salmonella expressing H. pylori urease have shown weak immunogenicity, resulting in a limited reduction in the H. pylori load in a few volunteers, 21,23,24,26,29 as well as safety issues and an immune response to the vaccine itself.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immune evaluation of aSaccharomyces cerevisiae‐based oral vaccine againstHelicobacter pyloriin mice

et al. 2020

View full text Add to dashboard Cite

Background Helicobacter pylori (H. pylori) is a common human pathogenic bacterium that is associated with gastric diseases. The current leading clinical therapy is combination antibiotics, but this treatment has safety issues, especially the induction of drug resistance. Therefore, developing a safe and effective vaccine against H. pylori is one of the best alternatives. Objective To develop Saccharomyces cerevisiae (S. cerevisiae)‐based oral vaccines and then demonstrate the feasibility of this platform for preventing H. pylori infection in the absence of a mucosal adjuvant. Materials and Methods Saccharomyces cerevisiae (S. cerevisiae)‐based oral vaccines, including EBY100/pYD1‐UreB and EBY100/pYD1‐VacA, were generated and analyzed by Western blot, Immunofluorescence analysis, flow cytometric assay, and indirect enzyme‐link immunosorbent assay (ELISA). Further, antibody responses induced by oral administration of EBY100/pYD1‐UreB, EBY100/pYD1‐VacA, or EBY100/pYD1‐UreB + EBY100/pYD1‐VacA were measured in a mouse model. Lastly, the vaccinated mice were infected with H. pylori SS1, and colonization in the stomach were evaluated. Results Saccharomyces cerevisiae‐based H. pylori oral vaccines were successfully constructed. Mice orally administered with EBY100/pYD1‐UreB, EBY100/pYD1‐VacA, or EBY100/pYD1‐UreB + EBY100/pYD1‐VacA exhibited a significant humoral immune response as well as a mucosal immune response. Importantly, S. cerevisiae‐based oral vaccines could effectively reduce bacterial loads with statistical significance after H. pylori infection. Conclusions Our study shows that S. cerevisiae‐based platforms can serve as an alternative approach for the future development of promising bacterial oral vaccine candidates.

show abstract

E. coli Enterotoxin LtB Enhances Vaccine-Induced Anti-H. pylori Protection by Promoting Leukocyte Migration into Gastric Mucus via Inflammatory Lesions

Cited by 8 publications

References 46 publications

Recombinant lactic acid bacteria as promising vectors for mucosal vaccination

Recombinant lactic acid bacteria as promising vectors for mucosal vaccination

Oral Administration of a Shigella 2aT32-Based Vaccine Expressing UreB-HspA Fusion Antigen With and Without Parenteral rUreB-HspA Boost Confers Protection Against Helicobacter pylori in Mice Model

Immune evaluation of aSaccharomyces cerevisiae‐based oral vaccine againstHelicobacter pyloriin mice

Contact Info

Product

Resources

About