Nongenetically modified <i>Lactococcus lactis</i>‐adjuvanted vaccination enhanced innate immunity against <i>Helicobacter pylori</i>

Liu, Wei; Tan, Zhoulin; Liu, Hai; Zeng, Zhiqing; Luo, Shuanghui; Yang, Hee-Deok; Zheng, Lufeng; Xi, Tao; Xing, Yingying

doi:10.1111/hel.12426

Cited by 12 publications

(13 citation statements)

References 43 publications

(59 reference statements)

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“…Gastric RNA extraction and reverse transcription were carried out as described previously (22). PCR amplification was performed with a conventional TaqMan method.…”

Section: Methodsmentioning

confidence: 99%

“…Helicobacter pylori SS1 was cultured as previously described (22). Sixty days after the last vaccination, the mice were challenged with 1 × 10 9 CFU H. pylori SS1 (determined by turbidimetry) by gavage in 200 μl of 0.2% sodium bicarbonate solution.…”

Section: Methodsmentioning

confidence: 99%

“…Quantitative culture of H. pylori was performed as previously described (22). Briefly, half of the stomach was homogenized in 500 μl Brain Heart Infusion (BHI) broth and plated at a series of dilutions on BHI plates.…”

Section: Methodsmentioning

confidence: 99%

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Gastric Subserous Vaccination With Helicobacter pylori Vaccine: An Attempt to Establish Tissue-Resident CD4+ Memory T Cells and Induce Prolonged Protection

et al. 2019

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Tissue-resident memory T (Trm) cells are enriched at the sites of previous infection and required for enhanced protective immunity. However, the emergence of Trm cells and their roles in providing protection are unclear in the field of Helicobacter pylori ( H. pylori ) vaccinology. Here, our results suggest that conventional vaccine strategies are unable to establish a measurable antigen (Ag)-specific memory cell pool in stomach; in comparison, gastric subserous injection of mice with micro-dose of Alum-based H. pylori vaccine can induce a pool of local CD4+ Trm cells. Regional recruitment of Ag-specific CD4+ T cells depends on the engagement of Ag and adjuvant-induced inflammation. Prior subcutaneous vaccination enhanced this recruitment. A stable pool of Ag-specific CD4+ T cells can be detected for 240 days. Two weeks of FTY720 administration in immune mice suggests that these cells do not experience the recirculation. Immunohistochemistry results show that close to the vaccination site, abundant CD4+T cells locate on epithelial niches, independent of lymphocyte cluster. Paradigmatically, Ag-specific CD4+ T cells with a phenotype of CD69+CD103- are preferential on lymphocytes isolated from epithelium. Upon Helicobacter infection, CD4+ Trm cells orchestrate a swift recall response with the recruitment of circulating antigen-specific Th1/Th17 cells to trigger a tissue-wide pathogen clearance. This study investigates the vaccine-induced gastric CD4+ Trm cells in a mice model, and highlights the need for designing a vaccine strategy against H. pylori by establishing the protective CD4+ Trm cells.

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“…Gastric RNA extraction and reverse transcription were carried out as described previously (22). PCR amplification was performed with a conventional TaqMan method.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Gastric Subserous Vaccination With Helicobacter pylori Vaccine: An Attempt to Establish Tissue-Resident CD4+ Memory T Cells and Induce Prolonged Protection

et al. 2019

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“…Then the leukocytes accumulated near the epithelium may have chance to leak or migrate to the mucus layer via the epithelial injury, approach H. pylori and destroy these mucus-colonizing bacteria, as shown in Figure 10 [34,40]. In short, we thought the LtB-adjuvanted protective immune effect against H. pylori involves a sequential process of LtB-aggravated inflammatory response, leukocytes accumulation and degranulation, mucosal injury, or leukocytes’ leaking into the mucus layer and killing the microbes with/without acquired specific immunity [41,42,43]. This novel viewpoint might thresh light on the mechanism beneath the cellular immune protection against such organisms as H. pylori, ETEC and some Shigella species, which are predominantly non-invasive, commonly colonize mucosal surface.…”

Section: Discussionmentioning

confidence: 99%

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

Peng

Zhang

Wang

et al. 2019

Cells

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Current studies indicate that the anti-H. pylori protective efficacy of oral vaccines to a large extent depends on using mucosal adjuvants like E. coli heat-lable enterotoxin B unit (LtB). However, the mechanism by which Th17/Th1-driven cellular immunity kills H. pylori and the role of LtB remains unclear. Here, two L. lactis strains, expressing H. pylori NapA and LtB, respectively, were orally administrated to mice. As observed, the administration of LtB significantly enhanced the fecal SIgA level and decreased gastric H. pylori colonization, but also markedly aggravated gastric inflammatory injury. Both NapA group and NapA+LtB group had elevated splenocyte production of IL-8, IL-10, IL-12, IL-17, IL-23 and INF-γ. Notably, gastric leukocytes’ migration or leakage into the mucus was observed more frequently in NapA+LtB group than in NapA group. This report is the first that discusses how LtB enhances vaccine-induced anti-H. pylori efficacy by aggravating gastric injury and leukocytes’ movement into the mucus layer. Significantly, it brings up a novel explanation for the mechanism underlying mucosal cellular immunity destroying the non-invasive pathogens. More importantly, the findings suggest the necessity to further evaluate LtB’s potential hazards to humans before extending its applications. Thus, this report can provide considerable impact on the fields of mucosal immunology and vaccinology.

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“…Adjuvants, namely immunomodulators, are small molecules that enhance the immunogenicity of vaccines to improve pathogen suppression and reduce the vaccine dose. While classical adjuvants, such as potassium alum, have been frequently used, subsequent studies have generated novel candidates (Arzeno Carranza, 1950;Sjokvist Ottsjo et al, 2013;Liu et al, 2017;Longet et al, 2019). For anti-H. pylori vaccines, cholera toxin (CT) and Escherichia coli heat-labile enterotoxin (LT) are widely used as adjuvants to boost the efficacy of mucosal vaccines in mice (Lehours and Ferrero, 2019).…”

Section: Introductionmentioning

confidence: 99%

Outer Membrane Vesicles of Helicobacter pylori 7.13 as Adjuvants Promote Protective Efficacy Against Helicobacter pylori Infection

Song

Zhang

et al. 2020

Front. Microbiol.

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Helicobacter pylori(H. pylori), a gram-negative bacterium in the human stomach with global prevalence, is relevant to chronic gastrointestinal diseases. Due to its increasing drug resistance and the low protective efficacy of some anti-H. pylori vaccines, it is necessary to find a suitable adjuvant to improve antigen efficiency. In our previous study, we determined that outer membrane vesicles (OMVs), a multicomponent secretion generated by gram-negative bacteria, of H. pylori were safe and could induce long-term and robust immune responses against H. pylori in mice. In this study, we employed two common vaccines, outer membrane proteins (OMPs) and whole cell vaccine (WCV) to assess the adjuvanticity of OMVs in mice. A standard adjuvant, cholera toxin (CT), was used as a control. Purified H. pylori OMVs used as adjuvants generated lasting anti-H. pylori resistance for 12 weeks. Additionally, both systematic and gastric mucosal immunity, as well as humoral immunity, of mice immunized with vaccine and OMVs combinations were significantly enhanced. Moreover, OMVs efficiently promoted Th1 immune response, but the response was skewed toward Th2 and Th17 immunity when compared with that induced by the CT adjuvant. Most importantly, OMVs as adjuvants enhanced the eradication of H. pylori. Thus, OMVs have potential applications as adjuvants in the development of a new generation of vaccines to treat H. pylori infection.

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Nongenetically modified Lactococcus lactis‐adjuvanted vaccination enhanced innate immunity against Helicobacter pylori

Abstract: These findings suggest that GEM-based vaccine may impact Th1/Th17 immunity to orchestrate innate immune response against H. pylori infection.

Cited by 12 publications

References 43 publications

Gastric Subserous Vaccination With Helicobacter pylori Vaccine: An Attempt to Establish Tissue-Resident CD4+ Memory T Cells and Induce Prolonged Protection

Gastric Subserous Vaccination With Helicobacter pylori Vaccine: An Attempt to Establish Tissue-Resident CD4+ Memory T Cells and Induce Prolonged Protection

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

Outer Membrane Vesicles of Helicobacter pylori 7.13 as Adjuvants Promote Protective Efficacy Against Helicobacter pylori Infection

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