Delivery of Helicobacter pylori HpaA to gastrointestinal mucosal immune sites using Lactococcus lactis and its immune efficacy in mice

Zhang, Rongguang; Wang, Chen; Cheng, Wei; Shi, Qingfeng; Chen, Shuaiyin; Fan, Qi-Wen

doi:10.1007/s10529-017-2502-3

Cited by 12 publications

(3 citation statements)

References 14 publications

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“…As an alternative to classical vaccines, two groups engineered recombinant Lactococcus lactis strains to overexpress H. pylori antigens: (a) the complete H. pylori adhesin A (HpaA), a lipoprotein located in the cellular outer membrane and flagellum sheath, and (b) the neutrophil‐activating protein A subunit (NapA), a virulence factor that recruits and stimulates neutrophils and protects H. pylori against oxidative damage . Animals inoculated once a week for four weeks with the recombinant L. lactis strain developed anti‐HpaA and anti‐NapA IgG, and fecal IgA . The immunization with the NapA‐expressing L. lactis strain also initiated a Th1 and Th17 response by splenic cells under an antigenic recall assay using H. pylori lysates, a partial reduction in H. pylori colonization, but no significant change in the level of gastritis.…”

Section: Vaccinesmentioning

confidence: 99%

“…44 Animals inoculated once a week for four weeks with the recombinant L. lactis strain developed anti-HpaA and anti-NapA IgG, and fecal IgA. 42,43 The immunization with the NapAexpressing L. lactis strain also initiated a Th1 and Th17 response by splenic cells under an antigenic recall assay using H. pylori lysates, a partial reduction in H. pylori colonization, 43…”

Section: Vacci N E Smentioning

confidence: 99%

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Helicobacter: Inflammation, immunology, and vaccines

et al. 2018

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Helicobacter pylori infection induces a chronic gastric inflammation which can lead to gastric ulcers and cancer. The mucosal immune response to H. pylori is first initiated by the activation of gastric epithelial cells that respond to numerous bacterial factors, such as the cytotoxin-associated gene A or the lipopolysaccharide intermediate heptose-1,7-bisphosphate. The response of these cells is orchestrated by different receptors including the intracellular nucleotide-binding oligomerization domain-containing protein 1 or the extracellular epidermal growth factor receptor. This nonspecific response leads to recruitment and activation of various myeloid (macrophages and dendritic cells) and T cells (T helper-17 and mucosal-associated invariant T cells), which magnify and maintain inflammation. In this review, we summarize the major advances made in the past year regarding the induction, the regulation, and the role of the innate and adaptive immune responses to H. pylori infection. We also recapitulate efforts that have been made to develop efficient vaccine strategies.

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Section: Vaccinesmentioning

confidence: 99%

Section: Vacci N E Smentioning

confidence: 99%

Helicobacter: Inflammation, immunology, and vaccines

et al. 2018

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“…They can recognize and bind to receptors on epithelial cells of the gastric mucosa to facilitate H. pylori to establish a successful infection (5)(6)(7)(8). Among them, neuraminyllactose-binding hemagglutinin (HpaA), a highly conserved lipoprotein (9), regulates the colonization and other different stages of the pathogenic process of H. pylori, and is expected to be a target for H. pylori treatment (10).…”

Section: Introductionmentioning

confidence: 99%

Adhesin HpaA of Helicobacter pylori Promoted Migration of AGS Cells via IL-21 Secretion from HpaA-induced CD4+T Cells

Xia

Hua

et al. 2020

Jundishapur J Microbiol

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Background: As known, there is a high correlation between Helicobacter pylori infection and gastric carcinoma. Objectives: Concerning the important role of adhesin HpaA of H. pylori in the infection process, we aimed to explore whether HpaA promotes gastric cancer metastasis. Methods: In this study, the levels of IL-21, MMP-2, and MMP-9 in patients’ biopsies with H. pylori infection were compared with post-treatment condition. The levels of IL-21 from CD4+ T cells and culture supernatants with the recombinant HpaA treatment were detected, and then the levels of MMP-2, MMP-9, and metastasis were detected and verified via AGS cells co-cultured with aforesaid CD4+ T cells. Results: Our results showed that higher levels of IL-21, MMP-2, and MMP-9 in patients’ biopsies with H. pylori infection than without H.pylori infection. Adhesin HpaA induced more IL-21 via CD4+ T cells, and IL-21 induced high MMP-2 and MMP-9 via AGS cells. In particular, HpaA caused this serial reaction to improve the migration of AGS cells, and aptamer HA6 (our previous report) and anti-IL-21 mcAb reduced the above phenomenon remarkably. Conclusions: In summary, our research suggested that adhesin HpaA plays a significant role in the process of gastric carcinoma cell metastasis via IL-21 from HpaA-induced T cells, and aptamer HA6 may be a potential therapeutic agent for H. pylori treatment.

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Recombinant lactic acid bacteria as promising vectors for mucosal vaccination

Qiao

Zhong

et al. 2021

Exploration

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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.

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Delivery of Helicobacter pylori HpaA to gastrointestinal mucosal immune sites using Lactococcus lactis and its immune efficacy in mice

Abstract: A novel engineered L. lactis strain was developed that efficiently produces whole HpaA protein with desired antigenicity and potent immunogenicity. It provides a basis for approaches to L. lactis-delivered anti-H. pylori vaccination.

Cited by 12 publications

References 14 publications

Helicobacter: Inflammation, immunology, and vaccines

Helicobacter: Inflammation, immunology, and vaccines

Adhesin HpaA of Helicobacter pylori Promoted Migration of AGS Cells via IL-21 Secretion from HpaA-induced CD4+T Cells

Recombinant lactic acid bacteria as promising vectors for mucosal vaccination

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