Chitosan-LeoA-DNA Nanoparticles Promoted the Efficacy of Novel LeoA-DNA Vaccination on Mice Against Helicobacter pylori.

More than half of the world's population is infected with Helicobacter pylori (H. pylori), which may lead to chronic gastritis, peptic ulcers, and stomach cancer. LeoA, a conserved antigen of H. pylori, aids in preventing this infection by triggering specific CD3+ T-cell responses. In this study, recombinant plasmids containing the LeoA gene of H. pylori are created and conjugated with chitosan nanoparticle (CSNP) to immunize BALB/c mice against the H. pylori infection. We used the online Vaxign tool to analyze the genomes of five distinct strains of H. pylori, and we chose the outer membrane as a prospective vaccine candidate. Afterward, the proteins' immunogenicity was evaluated. The DNA vaccine was constructed and then encapsulated in CSNPs. The effectiveness of the vaccine's immunoprotective effects was evaluated in BALB/c mice. Purified activated splenic CD3+ T cells are used to test the anticancer effects in vitro. Nanovaccines had apparent spherical forms, were small (mean size, 150-250 nm), and positively charged (41.3 ± 3.11 mV). A consistently delayed release pattern and an entrapment efficiency (73.35 ± 3.48%) could be established. Compared to the non-encapsulated DNA vaccine, vaccinated BALB/c mice produced higher amounts of LeoA-specific IgG in plasma and TNF-α in splenocyte lysate. Moreover, BALB/c mice inoculated with nanovaccine demonstrated considerable immunity (87.5%) against the H. pylori challenge and reduced stomach injury and bacterial burdens in the stomach. The immunological state in individuals with GC with chronic infection with H. pylori is mimicked by the H. pylori DNA nanovaccines by inducing a shift from Th1 to Th2 in the response. In vitro human GC cell development is inhibited by activated CD3+ T lymphocytes. According to our findings, the H. pylori vaccine-activated CD3+ has potential immunotherapeutic benefits.

Evaluation of the relationship between atherosclerosis and Helicobacter pylori infection with measurement of growth differentiation factor 15 and atherosclerosis indicators in adults with no comorbidity / Evaluación de la relación entre aterosclerosis e infección por Helicobacter pylori con medición del factor de diferenciación de crecimiento 15 e indicadores de aterosclerosis en adultos sin comorbilidad

Background The aim of this study was to investigate presence of subclinical atherosclerosis by measuring carotid intima-media thickness (CIMT) in patients with Helicobacter pylori (HP) and to assess effects of HP on atherosclerosis by evaluating markers of atherosclerosis and blood growth differentiation factor (GDF-15) levels. Materials and methods This cross-sectional study included 59 patients without comorbid disease who had HP and 30 healthy controls without HP in upper endoscopic biopsy. In order to assess atherosclerosis, the CIMT measurement was performed by sonography. Serum GDF-15 level was measured by ELISA method. In all patients, atherosclerosis markers were recorded. Atherogenic indices were calculated, including Castelli risk index I and II (TG/HDL-c and LDL-c/HDL-c, respectively), plasma atherogenic index (PAI; log TG/HDL-c), non-HDL-c (TH-HDL-c) and atherogenic coefficient (AC; non-HDL-HDL-c). Results The GDF-15 level and CIMT were significantly higher in HP-positive group when compared to HP-negative group (p≤0.001). There was a significant correlation between serum GDF-15 level and CIMT (r=0.445; p≤0.001). There was no correlation between other atherosclerosis markers and serum GDF-15 level or CIMT. The bacterial intensity on endoscopic specimen was only correlated with CIMT (p<0.001). Vitamin B12 and D levels were comparable among groups. Conclusion This study suggested that there was a correlation between GDF-15 level and subclinical atherosclerosis development in patients with HP. However, GDF-15 level, which was found to be elevated while atherogenic indices were normal, can be an earlier marker for subclinical atherosclerosis. (AU)

Antecedentes El objetivo de este estudio fue investigar la presencia de aterosclerosis subclínica mediante la medición del grosor íntima-media de la carótida (GIMC) en pacientes con Helicobacter pylori y evaluar los efectos de H.pylori sobre la aterosclerosis mediante la evaluación de marcadores de aterosclerosis y de niveles de factor de diferenciación del crecimiento sanguíneo (growth differentiation factor 15 [GDF-15]). Materiales y métodos Este estudio transversal incluyó 59 pacientes sin enfermedad comórbida que tenían H.pylori y 30 controles sanos sin H.pylori en la biopsia endoscópica superior. Para evaluar la aterosclerosis, la medición de GIMC se realizó mediante ecografía. El nivel de GDF-15 en suero se midió mediante el método ELISA. En todos los pacientes se registraron marcadores de aterosclerosis. Se calcularon los índices aterogénicos, incluyendo el índice de riesgo de Castelli I y II (TG/cHDL y cLDL-cHDL, respectivamente), el índice aterogénico plasmático (PAI; log TG/HDL-c), no-cHDL (TH-cHDL) y el coeficiente aterogénico (no-HDL-cHDL). Resultados Los niveles de GDF-15 y de GIMC fueron significativamente más altos en el grupo H.pylori positivo en comparación con el grupo H.pylori negativo (p≤0,001). Hubo una fuerte correlación entre el nivel sérico de GDF-15 y el GIMC (r=0,445; p≤0,001). No hubo correlación entre otros marcadores de aterosclerosis y el nivel sérico de GDF-15 o GIMC. La intensidad bacteriana en la muestra endoscópica solo se correlacionó con GIMC (p≤0,001). Los niveles de vitaminaB12 y de vitaminaD fueron comparables entre los grupos. Conclusión Este estudio sugirió que había una correlación entre el nivel de GDF-15 y el desarrollo de aterosclerosis subclínica en pacientes con H.pylori. Sin embargo, el nivel de GDF-15, que se encontró elevado mientras que los índices aterogénicos eran normales, puede ser un marcador temprano de aterosclerosis subclínica. (AU)

[Cost-effectiveness analysis of a vaccine for Helicobacter pylori in southern Europe]. / Análisis coste-efectividad de una vacuna para Helicobacter pylori en el sur de Europa.

OBJECTIVE: There is sufficient evidence on the feasibility of a vaccine to prevent Helicobacter pylori infection. Modeling studies in low prevalence environments report a very probable long-term cost-effectiveness. The objective of this study was to quantify its efficiency in a local context. METHODS: The evolution of a cohort of newborns was simulated through a compartmental model representing a series of clinical situations regarding H. pylori infection and related diseases. The model was run under the assumption of both vaccination in the first year of life and no intervention. The time horizon was set as equivalent to the life expectancy and the perspective of the health system was taken into account. RESULTS: Vaccination against H. pylori would cost an average of €2,168/person more than no intervention. This would yield an average additional 0.32 quality-adjusted life years gained (QALY), which would entail an incremental cost-effectiveness ratio (ICER) of €7,196/QALY. For a willingness to pay of €24,506/QALY, 99.96% of the simulations were cost-effective at eighty-four years old. This threshold was crossed thirty years after vaccination. The variables that carried the most weight in explaining the variability of the ICER were, in this order, vaccine effectiveness, the incidence of infection in young children, and the price of the vaccine. Vaccination would cease to be cost-effective with a price greater than €3,634/dose or with effective population coverage less than 11%. CONCLUSIONS: When implemented in an environment with the epidemiological and economic characteristics of Southern Europe, a prophylactic vaccination against H. pylori would be cost-effective in the long run.

OBJECTIVE: Existen pruebas de la factibilidad de una vacuna para prevenir la infección por Helicobacter pylori. Modelizaciones en entornos de baja prevalencia informan de una muy probable coste-efectividad a largo plazo. El objetivo de este estudio fue cuantificar su eficiencia en un contexto local. METHODS: Se simuló la evolución de una cohorte de nacidos a través de un modelo compartimental representativo de varios estados clínicos en relación a la infección por H. pylori. Se ejecutó dicho modelo bajo las premisas de vacunación en el periodo de lactante y de no intervención. El horizonte temporal fue equivalente a la esperanza de vida y se tuvo en cuenta la perspectiva del sistema de salud. RESULTS: La vacunación frente a H. pylori costaría de media 2.168 €/persona más que la no intervención. Con ello se obtendrían 0,32 años de vida ganados ajustados por calidad (AVAC), lo que implicaría una razón de coste-efectividad incremental (RCEI) media de 7.196 €/AVAC. Para una disposición a pagar de 24.506 €/AVAC, el 99,96% de las simulaciones resultaron coste-efectivas al alcanzar el horizonte temporal y se cruzó dicho umbral a partir de los treinta años de la vacunación. Las variables que más peso tuvieron para explicar la variabilidad de la RCEI fueron, en este orden, la efectividad vacunal, la incidencia de la infección en la primera infancia y el precio de la vacuna. La vacunación dejaría de ser coste-efectiva con un precio mayor de 3.634€/vial o con una cobertura poblacional efectiva menor del 11%. CONCLUSIONS: Una vacunación frente a la infección por H. pylori administrada en la infancia sería coste-efectiva a largo plazo en un entorno con las características epidemiológicas y económicas del sur de Europa.

An intranasal influenza virus vector vaccine protects against Helicobacter pylori in mice.

Helicobacter pylori is a human pathogen that infects almost half of the population. Antibiotic resistance in H. pylori threatens health and increases the demand for prophylactic and therapeutic vaccines. Traditional oral vaccine research faces considerable challenges because of the epithelial barrier, potential enterotoxicity of adjuvants, and the challenging conditions of the gastric environment. We developed an intranasal influenza A virus (IAV) vector vaccine based on two live attenuated influenza viruses with modified acidic polymerase protein (PA) genes encoding the A subunit of H. pylori neutrophil-activating protein (NapA), named IAV-NapA, including influenza virus A/WSN/33 (WSN)-NapA and A/Puerto Rico/8/34 (PR8)-NapA. These recombinant influenza viruses were highly attenuated and exhibited strong immunogenicity in mice. Vaccination with IAV-NapA induced antigen-specific humoral and mucosal immune responses while stimulating robust Th1 and Th17 cell immune responses in mice. Our findings suggest that prophylactic and therapeutic vaccination with influenza virus vector vaccines significantly reduces colonization of H. pylori and inflammation in the stomach of mice.IMPORTANCEHelicobacter pylori is the most common cause of chronic gastritis and leads to severe gastroduodenal pathology in some patients. Many studies have shown that Th1 and Th17 cellular and gastric mucosal immune responses are critical in reducing H. pylori load. IAV vector vaccines can stimulate these immune responses while overcoming potential adjuvant toxicity and antigen dosing issues. To date, no studies have demonstrated the role of live attenuated IAV vector vaccines in preventing and treating H. pylori infection. Our work indicates that vaccination with IAV-NapA induces antigen-specific humoral, cellular, and mucosal immunity, producing a protective and therapeutic effect against H. pylori infection in BALB/c mice. This undescribed H. pylori vaccination approach may provide valuable information for developing vaccines against H. pylori infection.

Potential Gastric Cancer Immunotherapy: Stimulating the Immune System with Helicobacter pylori pIRES2-DsRed-Express-ureF DNA Vaccines.

Most gastric cancers (GC) are thought to be caused by Helicobacter pylori (H. pylori) infections. However, there is mounting evidence that GC patients with positive H. pylori status have improved prognoses. The H. pylori-induced cellular immune reaction may inhibit cancer. In this study, BALB/c mice were immunized using recombinant plasmids that encode the ureF gene of H. pylori. Purified functional splenic CD3+ T lymphocytes are used to study the anticancer effects in vitro and in vivo. The immunological state of GC patients with ongoing H. pylori infection is mimicked by the H. pylori DNA vaccines, which cause a change in the reaction from Th1 to Th2. Human GC cells grow more slowly when stimulated CD3+ T lymphocytes are used as adoptive infusions because they reduce GC xenograft development in vivo. The more excellent ratios of infiltrating CD8+/CD4+ T cells, the decreased invasion of regulatory FOXP3+ Treg lymphocytes, and the increased apoptosis brought on by Caspase9/Caspase-3 overexpression and Survivin downregulation may all contribute to the consequences. Our findings suggest that in people with advanced GC, H. pylori pIRES2-DsRed-Express-ureF DNA vaccines may have immunotherapeutic utility.

An M cell-targeting recombinant L. lactis vaccine against four H. pylori adhesins.

The acidic environment and enzyme degradation lead to oral vaccines often having little immune effect. Therefore, it is an attractive strategy to study an effective and safe oral vaccine delivery system that can promote gastrointestinal mucosal immune responses and inhibit antigen degradation. Moreover, the antigens uptake by microfold cells (M cells) is the determining step in initiating efficient immune responses. Therefore, M cell-targeting is one promising approach for enhancing oral vaccine potency. In the present study, an M cell-targeting L. lactis surface display system (plSAM) was built to favor the multivalent epitope vaccine antigen (FAdE) to achieve effective gastrointestinal mucosal immunity against Helicobacter pylori. Therefore, a recombinant Lactococcus lactic acid vaccine (LL-plSAM-FAdE) was successfully prepared, and its immunological properties and protective efficacy were analyzed. The results showed that LL-plSAM-FAdE can secretively express the recombinant proteins SAM-FAdE and display the SAM-FAdE on the bacterial cell surface. More importantly, LL-plSAM-FAdE effectively promoted the phagocytosis and transport of vaccine antigen by M cells in the gastrointestinal tract of mice, and simulated high levels of cellular and humoral immune responses against four key H. pylori adhesins (Urease, CagL, HpaA, and Lpp20) in the gastrointestinal tract, thus enabling effective prevention of H. pylori infection and to some extent eliminating H. pylori already present in the gastrointestinal tract. KEY POINTS: • M-cell-targeting L. lactis surface display system LL- plSAM was designed • This system displays H. pylori vaccine-promoted phagocytosis and transport of M cell • A promising vaccine candidate for controlling H. pylori infection was verified.

Oral administration of DNA alginate nanovaccine induced immune-protection against Helicobacter pylori in Balb/C mice.

BACKGROUND: Helicobacter pylori (H. Pylori), is an established causative factor for the development of gastric cancer and the induction of persistent stomach infections that may lead to peptic ulcers. In recent decades, several endeavours have been undertaken to develop a vaccine for H. pylori, although none have advanced to the clinical phase. The development of a successful H. pylori vaccine is hindered by particular challenges, such as the absence of secure mucosal vaccines to enhance local immune responses, the absence of identified antigens that are effective in vaccinations, and the absence of recognized indicators of protection. METHODS: The DNA vaccine was chemically cloned, and the cloning was verified using PCR and restriction enzyme digestion. The efficacy of the vaccination was investigated. The immunogenicity and immune-protective efficacy of the vaccination were assessed in BALB/c mice. This study demonstrated that administering a preventive Alginate/pCI-neo-UreH Nanovaccine directly into the stomach effectively triggered a robust immune response to protect against H. pylori infection in mice. RESULTS: The level of immune protection achieved with this nano vaccine was similar to that observed when using the widely accepted formalin-killed H. pylori Hel 305 as a positive control. The Alginate/pCI-neo-UreH Nanovaccine composition elicited significant mucosal and systemic antigen-specific antibody responses and strong intestinal and systemic Th1 responses. Moreover, the activation of IL-17R signaling is necessary for the defensive Th1 immune responses in the intestines triggered by Alginate/pCI-neo-UreH. CONCLUSION: Alginate/pCI-neo-UreH is a potential Nanovaccine for use in an oral vaccine versus H. pylori infection, according to our findings.

A Bifidobacterium animalis subsp. lactis strain that can suppress Helicobacter pylori: isolation, in vitro and in vivo validation.

The administration of probiotics is an effective approach for treatment of Helicobacter pylori, which is associated with human gastrointestinal diseases and cancers. To explore more effective probiotics for H. pylori infection elimination, bacteria from infant feces were screened in this study. We successfully isolated the Bifidobacterium animalis subsp. lactis strains and evaluated its efficacy to inhibit H. pylori growth in vitro and in vivo. The results showed that a B. animalis strain (named BB18) sustained a high survival rate after incubation in gastric juice. The rapid urease test suggested that B. animalis BB18 reduced pathogen loads in H. pylori-infected Mongolian gerbils. Alleviation of H. pylori infection-induced gastric mucosa damage and decreased levels inflammatory cytokines were observed after the B. animalis BB18 administration. These findings demonstrated that B. animalis BB18 can inhibit H. pylori infection both in vitro and in vivo, suggesting its potential application for the prevention and eradication therapy of H. pylori infection.

Embedding of exogenous B cell epitopes on the surface of UreB structure generates a broadly reactive antibody response against Helicobacter pylori.

Since Helicobacter pylori (H. pylori) resistance to antibiotic regimens has increased, vaccination is becoming an increasingly important alternative therapy to control H. pylori infection. UreB, FlaA, AlpB, SabA, and HpaA proteins of H. pylori were previously proved to be used as candidate vaccine antigens. Here, we developed an engineered antigen based on a recombinant chimeric protein containing a structural scaffold from UreB and B cell epitopes from FlaA, AlpB, SabA, and HpaA. The multi-epitope chimeric antigen, named MECU, could generate a broadly reactive antibody response including antigen-specific antibodies and neutralising antibodies against H. pylori urease and adhesins. Moreover, therapeutic immunisation with MECU could reduce H. pylori colonisation in the stomach and protect the stomach in BALB/c mice. This study not only provides promising immunotherapy to control H. pylori infection but also offers a reference for antigen engineering against other pathogens.

The effect of Saccharomyces boulardii supplementation on Helicobacter pylori eradication in children: a systematic review and meta-analysis of Randomized controlled trials.

BACKGROUND: It is unclear whether Saccharomyces boulardii (S. boulardii) supplementation in standard triple therapy (STT) is effective in eradicating Helicobacter pylori (H. pylori) infection in children. We therefore conducted a meta-analysis of randomized controlled trials (RCTs) to assess the effect of S. boulardii supplementation on H. pylori eradication in children. METHODS: We conducted electronic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure and Wanfang database from the beginning up to September 2023. A random-effects model was employed to calculate the pooled relative risk (RR) with 95% confidence intervals (CI) through a meta-analysis. RESULTS: Fifteen RCTs (involving 2156 patients) were included in our meta-analysis. Results of the meta-analysis indicated that S. boulardii in combination with STT was more effective than STT alone (intention-to-treat analysis : 87.7% vs. 75.9%, RR = 1.14, 95% CI: 1.10-1.19, P < 0.00001; per-protocol analysis : 88.5% vs. 76.3%, RR = 1.15, 95% CI: 1.10-1.19, P < 0.00001). The S. boulardii supplementation group had a significantly lower incidence of total adverse events (n = 6 RCTs, 9.2% vs. 29.2%, RR = 0.32, 95% CI: 0.21-0.48, P < 0.00001), diarrhea (n = 13 RCTs, 14.7% vs. 32.4%, RR = 0.46, 95% CI: 0.37-0.56, P < 0.00001), and nausea (n = 11 RCTs, 12.7% vs. 21.3%, RR = 0.53, 95% CI: 0.40-0.72, P < 0.0001) than STT group alone. Similar results were also observed in the incidence of vomiting, constipation, abdominal pain, abdominal distention, epigastric discomfort, poor appetite and stomatitis. CONCLUSIONS: Current evidence indicated that S. boulardii supplementing with STT could improve the eradication rate of H. pylori, and concurrently decrease the incidence of total adverse events and gastrointestinal adverse events in children.

Anti-Helicobacter pylori activity and gastroprotective effects of human stomach-derived Lactobacillus paragasseri strain LPG-9.

The eradication of Helicobacter pylori is an urgent global issue. However, the traditional regimens have several limitations. Thus, we propose the idea of treating bacterial gastric disease with the objective of eliminating gastric pathogenic bacteria and enhancing gastroprotective effects using gastric probiotics. In this study, a total of 12 Lactobacillus strains were isolated from the gastric mucosa of healthy donors. After evaluation using a weight scoring system, Lactobacillus paragasseri strain LPG-9 was identified as the most promising probiotic for gastric disease, with the highest acid-resistance and the best adhesion characteristics. Gastric colonisation, H. pylori inhibition, anti-inflammatory, and gastric homeostasis effects of LPG-9 were confirmed in C57BL/6 mice. Finally, a safety evaluation and whole-genome sequencing were performed. Based on the results of this study, LPG-9 originates from the gastric microbiota and is a promising probiotic for gastric disease, particularly H. pylori-induced gastritis, providing a solution to this global issue.

Recombinant outer membrane vesicles delivering eukaryotic expression plasmid of cytokines act as enhanced adjuvants against Helicobacter pylori infection in mice.

The widespread prevalence of Helicobacter pylori (H. pylori) infection remains a great challenge to human health. The existing vaccines are not ideal for preventing H. pylori infection; thus, exploring highly effective adjuvants may improve the immunoprotective efficacy of H. pylori vaccines. In a previous study, we found that the outer membrane vesicles (OMVs), a type of nanoscale particle spontaneously produced by Gram-negative bacteria, could act as adjuvants to boost the immune responses to vaccine antigens. In this study, we explored the potential application of OMVs as delivery vectors for adjuvant development. We constructed recombinant OMVs containing eukaryotic expression plasmid of cytokines, including interleukin 17A or interferon-γ, and evaluated their function as adjuvants in combination with inactivated whole-cell vaccine (WCV) or UreB as vaccine antigens. Our results showed that recombinant OMVs as adjuvants could induce stronger humoral and mucosal immune responses in mice than wild-type H. pylori OMVs and the cholera toxin (CT) adjuvant. Additionally, the recombinant OMVs significantly promoted Th1/Th2/Th17-type immune responses. Furthermore, the recombinant OMV adjuvant induced more potent clearance of H. pylori than CT and wild-type OMVs. Our findings suggest that the recombinant OMVs coupled with cytokines may become potent adjuvants for the development of novel and effective vaccines against H. pylori infection.

Alcohol increases treatment failure for Helicobacter pylori eradication in Asian populations.

BACKGROUND AND AIM: Whether alcohol intake is associated with Helicobacter pylori (H. pylori) eradication failure remains controversial, and this meta-analysis was aimed at investigating the effect of alcohol on the risk of H. pylori eradication failure. METHODS: Relevant studies were systematically screened for and retrieved from PubMed and Web of Science (updated to January 2022), and relevant references were manually reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup, publication bias, and sensitivity analyses were also conducted. RESULTS: A total of 40 studies were included in the meta-analysis. No significant association was found between alcohol consumption and the risk of H. pylori eradication failure (OR = 1.09, 95% CI, 0.94-1.26). However, in subgroup analyses stratified by region, a positive association was found in Asian patients (OR = 1.23, 95% CI, 1.03-1.47). In Asian patients, alcohol consumption was associated with the risk of H. pylori eradication failure when the duration of therapy was > 7 days (OR = 1.17, 95% CI, 1.10-1.25), when the treatment regimen included nitroimidazoles (OR = 1.16, 95% CI, 1.09-1.24), and when patients were treated with bismuth-containing quadruple therapy (OR = 1.17, 95% CI, 1.10-1.25). Alcohol intake > 40 g/day was associated with H. pylori eradication failure (OR = 3.17, 95% CI, 1.56-6.41). Moreover, in Asian patients who were administered a vonoprazan (VPZ)-based therapy regimen, alcohol consumption had no effect on H. pylori eradication rates (OR = 1.73, 95% CI, 0.98-3.05). CONCLUSION: Our meta-analysis clearly showed that a higher daily alcohol intake was associated with a higher risk of H. pylori eradication failure in Asian populations. Moreover, a VPZ-based treatment regimen can prevent this effect.

Identification of the immunogenic membrane proteins, catalase, PgbA, and PgbB, as potential antigens against Helicobacter pylori.

AIMS: This study aims to investigate the specific membrane antigens that are targeted by antibodies raised against Helicobacter pylori. METHODS AND RESULTS: Bovine milk antibodies were prepared using whole H. pylori, purified membrane proteins, or both. Enzyme-linked immunosorbent assay and sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments revealed that these immunogens triggered anti-H. pylori antibody production in milk. The highest antibody titer was induced by the mixture of whole bacteria and purified membrane proteins. The antibodies induced by mixed immunogens significantly inhibited H. pylori growth in vitro and were used to identify catalase, plasminogen-binding protein A (PgbA), and PgbB via western blotting, immunoprecipitation, and two-dimensional western blotting followed by liquid chromatography with tandem mass spectrophotometry. The immunogenicity of PgbA and PgbB was verified in mice vaccinated with their B-cell epitope vaccines. Following prophylactic vaccination of C57BL/6 mice, each of the three antigens alone and their combination reduced the weight loss in mice, increased antibody titers, and relieved the inflammatory status of the gastric mucosa following H. pylori infection. CONCLUSIONS: Catalase, PgbA, and PgbB could serve as valuable membrane antigens for the development of anti-H. pylori immunotherapies.

Expression and purification of epitope vaccine against four virulence proteins from Helicobacter pylori and construction of label-free electrochemical immunosensor.

The epitope vaccine against four virulence proteins (FVpE) from Helicobacter pylori (H. pylori) was expressed and purified. Western blot and Enzyme-linked Immunosorbent Assays (ELISA) were used to identify and investigate the immunoreactivity of FVpE protein. The immune-sensing platform based on titanium carbide/colloidal gold nanoparticles@carbon nanofiber/ionic liquid composites electrode was constructed for immobilizing FVpE. Electrochemical impedance spectroscopy (EIS) was used to study the electrochemical properties of the modified electrodes. The relevant influenced factors were optimized including pH value, antigen concentration, and incubating time. The prepared H. pylori label-free electrochemical immunosensor was used for antibody detection using differential pulse voltammetry (DPV). Under the optimal experimental conditions, the linear ranges of H. pylori antibodies, including anti-H. pylori, cytotoxin-associated gene A (CagA), vacuolating cytotoxin-associated gene A (VacA), and urease A (UreA), were all 0.1-5 ng mL-1, except urease B (UreB, 0.1-4.5 ng mL-1). The selectivity study showed that other antibodies had little influence on the detection of H. pylori antibodies. The immunosensor could be used to detect serum samples, and the recoveries were in the range of 68.5%-100.5%.

Cost-effectiveness analysis of different screening strategies for helicobacter pylori infection in Iran: A model-based evaluation.

BACKGROUND: The World Health Organization recommends assessing screening for helicobacter pylori infection to lower gastric cancer (GC) rates. Therefore, we carried out a study to evaluate the cost-effectiveness of different H. pylori screening approaches in Iran. MATERIALS AND METHODS: We used a Markov model with a 50-year time horizon and health system perspective to compare four H. pylori screening strategies (endoscopy, serology, urea breath test [UBT], stool antigen test [SAT]) to no screening in the population aged 20 years and older in Iran. Model parameters were extracted from primary data and published studies. Cost data also came from medical records of 120 patients at different stages of GC. We calculated costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) for each strategy. Probabilistic sensitivity analysis (PSA) using Monte Carlo simulation tested the model's robustness. All analyses were done in TreeAge Pro 2020. RESULTS: All screening strategies provided more QALYs compared to no screening. Base-case analysis found the UBT strategy was the most cost-effective, with an ICER of 101,106,261.5 Iranian rial (IRR) per QALY gained, despite being more costly. No screening and endoscopy were dominated strategies, meaning they had higher costs but provided fewer effectiveness compared to other options. PSA showed at a willingness-to-pay (WTP) threshold of 316,112,349 IRR (Iran's GDP per capita) per QALY, UBT was the optimal strategy in 57.1% of iterations. CONCLUSION: This cost-effectiveness analysis found that screening for H. pylori may be cost-effective in Iran. Among the 4 screening strategies examined, UBT was the most cost-effective approach. Further studies should do cost-effectiveness analyses for specific age groups to optimize the benefits achieved with limited resources.

The effectiveness of treatment with probiotics in Helicobacter pylori eradication: results from an umbrella meta-analysis on meta-analyses of randomized controlled trials.

Background and aims: The purpose of this umbrella meta-analysis was to quantitatively summarize meta-analyses of randomized controlled trial (RCT) studies regarding the effects of probiotic supplementation on Helicobacter pylori (H. pylori) eradication. Methods: A thorough search of the electronic databases including PubMed, Web of Science, Embase, Scopus, and Google Scholar was carried out from the inception up to May 2022. For the evaluation of overall effect sizes, the pooled relative risk (RR) or odds ratio (OR) and their corresponding 95% confidence intervals (CI) were calculated. The random-effects model was used for the meta-analysis. Results: Overall, 18 eligible studies (47 278 participants in total) were included in the study. The findings revealed that probiotics have a beneficial impact on H. pylori eradication (pooled ESRR: 1.13; 95% CI: 1.11, 1.14, p < 0.01, and ESOR = 1.86, 95% CI: 1.70, 2.03, p < 0.01). Greater effects on H. pylori eradication were observed when higher doses (>10 × 1010 CFU) and mixed strains were supplemented. Conclusion: The present umbrella meta-analysis suggests that supplementation with probiotics may be considered as an efficient approach to ameliorate H. pylori complications, particularly probiotics with higher CFUs and mixed strains.

Prophylactic immunization to Helicobacter pylori infection using spore vectored vaccines.

BACKGROUND: Helicobacter pylori infection remains a major public health threat leading to gastrointestinal illness and increased risk of gastric cancer. Mostly affecting populations in developing countries no vaccines are yet available and the disease is controlled by antimicrobials which, in turn, are driving the emergence of AMR. MATERIALS AND METHODS: We have engineered spores of Bacillus subtilis to display putative H. pylori protective antigens, urease subunit A (UreA) and subunit B (UreB) on the spore surface. Following oral dosing of mice with these spores, we evaluated immunity and colonization in animals challenged with H. pylori. RESULTS: Oral immunization with spores expressing either UreA or UreB showed antigen-specific mucosal responses (fecal sIgA) including seroconversion and hyperimmunity. Following challenge, colonization by H. pylori was significantly reduced by up to 1-log. CONCLUSIONS: This study demonstrates the utility of bacterial spores for mucosal vaccination to H. pylori infection. The heat stability and robustness of Bacillus spores coupled with their existing use as probiotics make them an attractive solution for either protection against H. pylori infection or potentially for therapy and control of active infection.

Helicobacter pylori induces urease subunit B-specific CD8+ T cell responses in infected individuals via cytosolic pathway of cross-presentation.

BACKGROUND: Urease subunit B (UreB), a conserved and key virulence factor of Helicobacter pylori (H. pylori), can induce the host CD4+ T cell immune responses to provide protection, but less is known regarding CD8+ T cell responses. The characteristics of H. pylori-specific CD8+ T cell responses and the mechanism underlying antigen processing and presentation pathways remain unclear. This study was focus on protective antigen recombinant UreB (rUreb) to detect specific CD8+ T cell responses in vitro and elucidate the mechanism of UreB antigen processing and presentation. METHODS: The peripheral blood mononuclear cells (PBMCs) collected from H. pylori-infected individuals were stimulated with rUreB in vitro to detect specific CD8+ T cell responses after co-culture with rUreB-pulsed autologous hMDCs. Through blocking assay, we investigated the potential pathway of UreB antigen processing and presentation via the cytosolic pathway or vacuolar pathway. The cytokines production of UreB specific CD8+ T cell were evaluated as well. RESULTS: We demonstrated UreB can induce specific CD8+ T cell immune responses in H. pylori infected individuals. Importantly, we characterized that UreB were mainly processed by proteasome instead of lysosomal proteases and presented through cytosolic pathway of cross-presentation, which requires endoplasmic reticulum-Golgi transport and newly synthesized MHC-I molecules, to induce functional-specific CD8+ T cell (IFN-γ + TNF-α + Grz A+ Grz B+) responses. CONCLUSIONS: These results suggest that H. pylori UreB induces specific CD8+ T cell responses through cytosolic pathway of cross-presentation in infected individuals.

[Research progress of Helicobacter pylori vaccine].

Helicobacter pylori (Hp) is one of most common pathogens causing gastrointestinal disorder including gastric ulcer, duodenal ulcer and gastric cancer, etc. It has been verified as class I carcinogen by WHO. Nowadays, combination antibiotics and proton pump inhibitor are mainly used to erase Hp in clinical application. However, with the increased resistance of Hp, the vaccine against Hp might become the best strategy to eradicate Hp. Elements including urease, virulence factor, outer membrane protein, flagella, play an important role in Hp infection, colonization and reproduction. They have become potential candidate antigens in the development of Hp vaccine, as reported in previous studies. Presently, these antigens-centric vaccines have been tested in animal models. Therefore, this article reviews the studies on Hp vaccine with urease, virulence genes, outer membrane protein and flagella as their candidate antigens, in an attempt to provide insights for research in this regard.