| 1. |
- Akter, S., et al.
(författare)
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The frequency of circulating integrin alpha 4 beta 7(+) cells correlates with protection against Helicobacter pylori infection in immunized mice
- 2019
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 24:6
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic Helicobacter pylori infection is the cause of peptic ulcers in a subpopulation of individuals and a risk factor for the development of gastric cancer. A vaccine against H pylori infection can prevent the acquisition of the infection and protect against reinfections. Clinical trials to date evaluating the efficacy of H pylori vaccines in human challenge models have shown moderate to poor protection with difficulties in predicting efficacy. Thus, while further studies are needed to design an effective vaccine, we also need to find relevant correlates for vaccine efficacy. Objective To find immune correlates to vaccine efficacy, the frequencies of neutrophils, eosinophils and inflammatory monocytes and CD4(+) T-cell memory and mucosa homing integrin alpha 4 beta 7(+) cells were assessed by flow cytometry in the blood of mice after vaccination. Materials and Methods H pylori antigens and cholera toxin or the multiple mutant CT (mmCT) were administered via the sublingual (SL) and intragastric route (IG). The vaccinated mice were infected with H pylori strain SS1 bacteria, and colonization in the stomach and immune responses were evaluated. Results The H pylori vaccine was effective in reducing bacterial load in the stomach of mice and enhancing immune responses compared to unvaccinated infection controls. In the blood of mice after SL or IG route of vaccination, we observed changes in frequencies of innate and adaptive immune cell subsets compared to infection controls. Remarkably, the frequency of circulating mucosal homing alpha 4 beta 7(+)CD4(+) T cells after vaccination correlated with low bacterial load in the stomach of individual mice irrespective of the immunization route. Conclusions Our study shows that the innate and adaptive immune cell subsets can be measured in the blood after vaccination and that increased frequency of alpha 4 beta 7(+)CD4(+) in the blood after immunization could be used as a predictive marker for the efficacy of vaccine against H pylori infection.
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| 2. |
- Holmgren, Jan, 1944, et al.
(författare)
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Preclinical immunogenicity and protective efficacy of an oral Helicobacter pylori inactivated whole cell vaccine and multiple mutant cholera toxin: A novel and non-toxic mucosal adjuvant
- 2018
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 36:41, s. 6223-6230
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal vaccines against Helicobacter pylori consisting of either whole cell bacteria or recombinant antigens can induce immune protection against challenge in mice only when co-administrated with a strong mucosal adjuvant such as cholera toxin (CT) or Escherichia coli heat labile enterotoxin (LT). The strong enterotoxicity of these adjuvants however preclude their use in human vaccines. The recently developed multiple mutant CT (mmCT) is a strong, yet practically non-toxic novel mucosal adjuvant which here was admixed with a formalin-inactivated H. pylori whole cell vaccine (WCV) as a potential vaccine candidate against H. pylori infection. We report that intragastric immunizations with H. pylori WCV together with mmCT, similar to immunization with WCV together with CT, resulted in 50-125-fold reduction in colonization of H. pylori in the stomach of mice associated with rises in both serum IgG and intestinal-mucosal IgA anti-H. pylori antibody responses and strong T cell and IFN gamma and IL-17A cytokine responses. Data presented in this study also supports that the proposed vaccine can be grown in a bioreactor and would be effective against infection caused by a multitude of pathogenic H. pylori strains isolated from patients from various continents. The results warrant immunization studies in humans to evaluate the safety, immunogenicity and efficacy of the proposed H. pylori WCV and mmCT. (C) 2018 Published by Elsevier Ltd.
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| 3. |
- Sharma, T., et al.
(författare)
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Development of Hillchol (R), a low-cost inactivated single strain Hikojima oral cholera vaccine
- 2020
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 38:50, s. 7998-8009
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Tidskriftsartikel (refereegranskat)abstract
- Cholera remains an important global health problem with up to 4 million cases and 140,000 deaths annually. Oral cholera vaccines (OCVs) are now a cornerstone of the WHOs "Ending Cholera - A Global Roadmap to 2030" global program for the eventual elimination of cholera. There are currently three WHO prequalified OCVs available, Dukoral (R), Shanchol (R) and Euvichol-Plus (R). These vaccines are effective but due to a multiple strain composition and two different methods of inactivation, are complex and costly to manufacture. We describe here the characterization and industrial scale development of Hillchol (R); a novel, likely affordable single-component OCV for low and middle-income countries. Hillchol (R) consists of formalin-inactivated bacteria of a stable recombinant Vibrio cholerae O1 El Tor Hikojima serotype strain expressing approximately 50% each of Ogawa and Inaba O1 LPS antigens. The novel OCV can be manufactured on an industrial scale at a low cost. Hillchol (R) was well tolerated in animal toxicology studies and shown to have non-inferior oral immunogenicity in mice for both intestinalmucosal and serological immune responses when compared with a WHO-prequalified OCV. The optimized production of this single component OCV will reduce cost of OCV production and thus substantially increase vaccine availability. Based on these results, Hillchol (R) has been produced at a GMP facility and used successfully for clinical phase I/II studies. (C) 2020 MSD Wellcome Trust Hilleman Laboratories Pvt Ltd. Published by Elsevier Ltd.
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| 4. |
- Sjökvist Ottsjö, Louise, 1986, et al.
(författare)
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Induction of mucosal immune responses against Helicobacter pylori infection after sublingual and intragastric route of immunization
- 2017
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Ingår i: Immunology. - : Wiley. - 0019-2805. ; 150:2, s. 172-183
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Tidskriftsartikel (refereegranskat)abstract
- There is a current lack of effective mucosal vaccines against major gastroenteric pathogens and particularly against Helicobacter pylori, which causes a chronic infection that can lead to peptic ulcers and gastric cancer in a subpopulation of infected individuals. Mucosal CD4(+) T-cell responses have been shown to be essential for vaccine-induced protection against H. pylori infection. The current study addresses the influence of the adjuvant and site of mucosal immunization on early CD4(+) T-cell priming to H. pylori antigens. The vaccine formulation consisted of H. pylori lysate antigens and mucosal adjuvants, cholera toxin (CT) or a detoxified double-mutant heat-labile enterotoxin from Escherichia coli (dmLT), which were administered by either the sublingual or intragastric route. We report that in vitro, adjuvants CT and dmLT induce up-regulation of pro-inflammatory gene expression in purified dendritic cells and enhance the H. pylori-specific CD4(+) T-cell response including interleukin-17A (IL-17A), interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) secretion. In vivo, sublingual immunization led to an increased frequency of IL-17A(+), IFN-gamma(+) and TNF-alpha(+) secreting CD4(+) T cells in the cervical lymph nodes compared with in the mesenteric lymph nodes after intragastric immunization. Subsequently, IL-17A(+) cells were visualized in the stomach of sublingually immunized and challenged mice. In summary, our results suggest that addition of an adjuvant to the vaccine clearly activated dendritic cells, which in turn, enhanced CD4(+) T-cell cytokines IL-17A, IFN-gamma and TNF-alpha responses, particularly in the cervical lymph nodes after sublingual vaccination.
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