Determination of Helicobacter pylori CagA EPIYA types in Iranian isolates with different gastroduodenal disorders

Helicobacter pylori (H. pylori) cytotoxin-associated gene A protein (CagA) is the first bacterial oncoprotein identified in human gastric cancer. The carboxy terminus (C-terminus) of CagA may undergo polymorphisms to give different types of EPIYA motifs, which may exist in single or combination form within the infected host. Sequence variations in the 3′ region of the cagA impose a functional impact to the translated CagA protein. In this study, we characterize the diversity of the H. pylori CagA EPIYA types, their associations with their hosts’ clinical status, and the potential of using the whole 3′ region of cagA as a genetic marker for the identification of Iranian isolates from different geographic locations. H. pylori was detected in 71 out of 177 examined Iranian patients with different gastroduodenal disorders. Genotyping of the cagA variable EPIYA motif was screened by polymerase chain reaction and gene sequencing was performed for all the detected cagA positive isolates. Out of 44 cagA-positive isolates, there were EPIYA motifs of ABC (30 isolates), ABCC (4 isolates), ABCCC (1 isolate), mixed types (6 isolates) and new types (3 isolates). We termed the newly identified EPIYA segment as EPIYA- A-B/C. Sequence analysis also showed the presence of uncommon EPIYA-like motifs (EPIYT and QPIYP) in some isolates. It is postulated that EPIYA type conversion through the presence of different repetitive sequences give rise to these new strains. We also identified 3 sequence motifs which may be applied as genetic markers for Iranian strains. Furthermore, EPIYA types ABCC and EPIYA- A-B/C showed association with duodenitis and gastric cancer, respectively. Further study with a larger number of strains is necessary to confirm the proposed associations and the identified sequence motifs as genetic markers. In conclusion, our study demonstrates the dominancy of Western type cagA gene and the diversity of the CagA C-terminal region in the tested Iranian strains.     

#8 Esophageal and gastric cancer in the united states

PURPOSE: Historically, esophageal and gastric cancers have been considered as two cancers. Esophageal cancers were predominantly squamous cell carcinomas, stomach cancers were adenocarcinomas, tumors arose throughout each of the two organs, and rates for each were higher among blacks than whites. Recent observations suggest that there may be at least three, if not four, distinct epidemiologic and potentially etiologic entities: squamous cell carcinoma of the esophagus (SCE), adenocarcinoma of the esophagus (ACE) (arising in the distal region), proximal stomach or gastric cardia adenocarcinoma (GCA), and noncardia gastric adenocarcinoma (NGA).METHODS: We analyzed SEER incidence data for 1974–78 to 1994–98 by anatomic site and histologic type to describe these potentially different tumors, review known or suspected risk factors, and describe the trends in prevalence of these factors.RESULTS: SCE rates decreased after 1988 for all race-gender groups. In contrast, the incidence of ACE increased more than 400% among white males, and ACE rates surpassed those of SCE after 1988. ACE rates increased more than 300% among white females, rose 100% among black males, and also showed an upward trend among black women. NGA trends were generally downward. However, similar to ACE, GCA rates increased from 1974–78 to 1984–88, although to a lesser extent, and appear to have stabilized since then. With the decrease in NGA rates and the increase then stabilization in GCA rates, rates of GCA and NGA among white men were similar in 1994–98.CONCLUSIONS: Declines in the prevalence of smoking and drinking and increases in consumption of fresh fruits and vegetables may contribute to the downward trends in SCE. Increases in gastroesophageal reflux disease and obesity, and declines in Helicobactor pylori (H. pylori) infection may contribute to the upward trends in ACE. Reductions in NGA may be related to improved diet and reductions in smoking and H. pylori prevalence. Factors contributing to the rising incidence of GCA of the cardia during the 1970s and 1980s, but not the 1990s, are less clear.     

Environmental risk factors affecting transmission of Helicobacter pylori infection in Egypt

Background

Helicobacter pylori (H. pylori) infection varies remarkably between and within populations suggesting the role of socioeconomic-related environmental factors.

Aim

The aim of this study was to determine the prevalence of H. pylori among the studied population, to explore the effect of some environmental risk factors and lifestyle on the transmission of infection, and to study the association between this H. pylori bacterium and various noncontagious diseases.

Method

This cross-sectional study was conducted over 6 months in two Egyptian health clinics. Two hundred apparently healthy individuals from rural (Unshass) and urban (Nasr City) areas voluntarily participated in this study. A full detailed clinical assessment in the form of a questionnaire was designed for each individual to determine risk factors with specific emphasis on age, sex, and residence. The seroprevalence of H. pylori IgG antibodies was evaluated using the enzyme-linked immunosorbent assay (ELISA).

Results

In the urban group 28 subjects (28%) were H. pylori positive versus 54 subjects (54%) in the rural group. A significant relationship between H. pylori and poor sanitary conditions was detected; there was an association between H. pylori prevalence and gastric diseases, hepatic diseases, and hyperglycemia suggesting diabetes.

Conclusion

H. pylori infection was nearly twice as high in the rural group than in the urban one.     

Relation of Serum Ascorbic Acid to Helicobacter pylori Serology in US Adults: the Third National Health and Nutrition Examination Survey

Purpose: To examine the relation between serum ascorbic acid and Helicobacter pylori serology from a probability sample of US adults.

Subjects and Methods: Data from 6,746 adults (ages 20 to 90 years) enrolled in the Third National Health and Nutrition Examination Survey (NHANES III), 1988–1994 were analyzed. Multiple logistic regression models were examined taking into account sample weights and the complex survey design of NHANES III, and controlling for the effects of potential confounders. Because race appeared to modify the association between serum ascorbic acid and seropositivity to H. pylori, we conducted the analyses stratified by race.

Results: A total of 2,189 adults (32%) had a positive serology for H. pylori, and, of these, 1,175 (54%) were positive for the CagA antigen. Among whites, a 0.50 mg/dL increase in serum ascorbic acid level was associated with decreased seroprevalence of H. pylori (Odds Ratio (OR) = 0.89, 95% confidence interval (CI) CI 0.82–0.96, p < 0.01). In analyses that controlled for seroprevalence of H. pylori, a 0.50 mg/dL increase in serum ascorbic acid level among whites was independently associated with a decreased seroprevalence of the pathogenic cagA-positive strain of H. pylori (OR = 0.31, 95% CI 0.12–0.79, p < 0.05). Serum ascorbic acid levels were not significantly associated with H. pylori serology among non-whites (all p > 0.05).

Conclusions: Higher serum levels of ascorbic acid were associated with a decreased seroprevalence of H. pylori and of the pathogenic cagA-positive strain of H. pylori among whites. If these associations are related causally and are not the result of residual confounding by factors such as socioeconomic status, ascorbic acid may affect the risk of H. pylori infection and in turn, the risk for peptic ulcer disease and gastric cancer among white Americans.     

#93-S u.s.-mexico cohort study of Helicobacter pylori Infection in children

PURPOSE:Helicobacter pylori infection occurs frequently in early childhood; persistence leads to chronic digestive diseases in adults. The Pasitos Cohort Study follows children from El Paso, Texas, USA and Ciudad Juarez, Mexico at 6-month intervals to identify predictors of acquisition and persistence of H. pylori infection.METHODS: Pregnant women were recruited from El Paso WIC clinics and Mexican Social Security Institute maternal-child clinics in Juarez from April 1998 to October 2000. Active H. pylori infection is detected in children by the 13C-urea breath test; results are corrected for body-size-dependent metabolic variation using Klein's method.RESULTS: The seroprevalence of H. pylori at baseline was 74% in 360 Juarez mothers and 56% in 368 El Paso mothers. To date, 350, 295, 196, 153 infants had breath tests around 6, 12, 18, and 24 months of age, respectively; H. pylori prevalence in the children was 0.07 [95% Confidence interval (CI) 0.05–0.10], 0.14, [0.11–0.19], 0.17 [0.12–0.23], and 0.20 [0.14–0.27] for these four ages, respectively. The total follow-up time was 6181 person-months; 108 infants had one or more positive breath tests, thus, the incidence rate of first detectable infection was 0.21/year [95% CI, 0.17–0.25]. Incidence rates for subgroups: Juarez infants, 44/2260 person-months = 0.23/year [0.16–0.30]; El Paso infants, 64/3921 person-months = 0.20/year [0.15–0.24]; boys, 49/2976 person-months = 0.20/year [0.14–0.25]; girls, 59/3205 person-months = 0.22/year [0.16–0.28]; first year of age, 66/4243 person-months = 0.19/year [0.14–0.23]; second year of age, 31/1340 person-months = 0.28/year [0.18–0.38].CONCLUSION:H. pylori incidence rate from birth through age two years was similar in infants on both sides of the U.S.-Mexico border and varied little by sex; the rate increased in the second year of life relative to the first.     

Genotyping of Helicobacter pylori shows high diversity of strains circulating in central Vietnam

In Vietnam, the high prevalence of Helicobacter pylori infection represents a serious health problem. Virulence genes of H. pylori have been associated to increased risk of severe gastrointestinal diseases and the genetic background differs in geographical areas. We investigated cagA and vacA genotypes of H. pylori from dyspeptic patients from central Vietnam and the correlation with clinical outcomes; we also performed sequencing analysis of partial cagA gene.Overall, 84% of strains were cagA-positive, 75% were East-Asian type with a prevalence of vacAs1i1m1 and vacAs1i1m2 genotypes (66.7% and 33.3%, respectively) and 9% were Western type vacAs1i1m1 (n = 4) and vacAs1i1m2 (n = 4); vacAs1i2m2 (n = 4) and vacAs2i2m2 (n = 2) genotypes were associated to cagA-negative. Strains from gastric ulcer and cancer were of East-Asian type, while cagA-negative or Western strains were from gastritis and duodenal ulcer. H. pylori strains from gastric ulcer patients were predominantly vacAs1i1m1 compared to other vacA genotypes (p < 0.05). East-Asian type strains vacAs1i1m1 or vacAs1i1m2 were found in gastric cancer patients and also in less severe disease. Phylogenetic tree analysis of CagA sequences showed the co-circulation of H. pylori of different geographical origins with Western sequences closer related to Cambodia, one of the entry of Western strains in Southeast-Asia through human migrations. Sequence analysis revealed in two Western type strains a chimeric CagA-3′ region with identity with East-Asian CagA suggesting recombination event in the process of evolution among East-Asian and Western H. pylori strains. Moreover, polymorphism in CagA multimerization (CM) motif was observed including new East-Asian CM motifs. In conclusion, we have found in central Vietnam a geographically dependent diversity of cagA genotype, with higher rates of cagA-negative and Western-type strains compared with other nation's parts that can partly explain the lower risk of gastric cancer. The polymorphism of CM motifs may explain the variability of disease manifestations of vacAs1i1m1 and s1i1m2 East-Asian isolates.     

Therapeutic efficacy of oral immunization with attenuated Salmonella typhimurium expressing Helicobacter pylori CagA, VacA and UreB fusion proteins in mice model

Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. In the present study, attenuated Salmonella vector vaccines were constructed that expressed fusion proteins complexed with H. pylori CagA, VacA and UreB in different arrangements, and their therapeutic efficacy was evaluated in H. pylori-infected mice. Oral therapeutic immunization with attenuated Salmonella, which expressed the fused protein CVU, significantly decreased H. pylori colonization in the stomach; protection was related to specific CD4⁺ T cell Th1 type responses and serum IgG and mucosal sIgA antibody responses. These findings suggested that therapeutic efficacy was related to the arrangement of the fusion protein. It is possible that arrangement decides the expression of recombinant antigen in mice, and the latter results in different therapeutic efficacy. The attenuated Salmonella vector vaccine, which expressed the fused protein arrangement CVU, is superior to others, and could be a candidate vaccine against H. pylori.     

Colombia: the widening gap between health care reform and gastric cancer

The purpose of this paper is to discuss Colombia’s recent health care reform and subsequent social implications regarding gastric cancer, which is a common cancer in Colombia. This review explores the use of Helicobacter pylori prevalence classifying as an indicator of failing implementation of health policy, specifically H. pylori should be explored in the context of socioeconomic inequity. A review of the literature examining recent Colombian health care reform and H. pylori infection was conducted. H. pylori occur most frequently in impoverished populations. Gastric cancer (GC) is the main cause of mortality by cancer in Colombia, a South American country, which has a high prevalence of H. pylori in the population. Over the past 40 years, Colombia has undergone a revolutionary improvement in the health and social status of its population. In recent times, the country has faced a unique challenge as its government has grappled with the ongoing civil war with numerous war rebels. It is known that socioeconomic conditions, known to influence gastric cancer risk, are important determinants of H. pylori infection. The role of socioeconomic gradients in developing countries should be emphasized as a basis for etiological research; the disparity between the wealthy and poor is increasing over time. Colombia is currently undergoing major changes in disease-specific mortality rates, including an increasing burden of cancer death.     

Prevalence of Helicobacter pylori cagA genotype among dyspeptic patients in Southern Thailand

ObjectiveTo investigate the prevalence of Helicobacter pylori (H. pylori) infection in dyspepsia patients and its relation to virulence factor cagA gene.MethodsIn total, 110 gastric biopsies from dyspeptic patients were comparatively studied using rapid urease test and multiplex PCR. Multiplex PCR detected three genes of 16S rRNA, cagA, and ureC.ResultsH. pylori was detected in 14 gastric biopsies (13%). Significantly higher number of female were infected. Furthermore, cagA gene was found in all H. pylori–positive specimens. In addition, the result indicated that the multiplex PCR with annealing temperature at 57 oC was able to effectively amplify specific products.ConclusionThe results confirmed that high preva¬lence of cagA gene in H. pylori among dyspeptic patients in Southern Thailand.     

Seroprevalence of <Emphasis Type="Italic">Helicobacter pylori</Emphasis> in New York City populations originating in East Asia

Helicobacter pylori prevalence is higher in developing countries than in industrialized countries, and within the latter, higher among immigrants than among nativeborn residents. Using a point-prevalence survey, we sought to identify risk factors for H. pylori seropositivity in US urban East Asian-born populations. At a clinic in New York City, we consecutively enrolled 194 East Asian-born adults, who then responded to a survey and provided a blood sample. Assays were performed to detect IgG antibodies against whole cell (WC) and cytotoxin associated gene A (CagA) antigens of H. pylori. For this group (mean age 50.2±14.7 years), the mean period of residence in the Unites States was 11.9±7.7 years. The total H. pylori seroprevalence was 70.1%, with highest (81.4%) in Fujianese immigrants. Multiple logistic regression analysis indicated an independent association of H. pylori seropositivity with Fujianese origin [odds ratios (OR)=2.3,95% confidence interval (95% Cl)=1.05–5.0] and inverse associations with period in the United States (OR per year of residency in the United States=0.95, 95% Cl=0.91–0.99) and with a history of dyspepsia (OR for a history of stomach pain=0.52,95% Cl=0.3–1.0). We conclude that H. pylori is highly prevalent among recent East Asian immigrants, especially among Fujianese. The protective effects of history of dyspepsia and duration in the United States suggest that these may be markers for antibiotic therapies.     

Single-nucleotide polymorphisms in Toll-like receptor genes are associated with the prognosis of gastric cancer and are not associated with Helicobacter pylori infection

Toll-like receptors (TLRs) mediate the recognition of Helicobacter pylori (H. pylori) and initiate the innate immune response to infection. Genetic polymorphisms of TLRs play important roles in gastric carcinogenesis. The aim of this study was to determine the association between single nucleotide polymorphisms (SNPs) in TLR genes and H. pylori infection in the prognosis of gastric cancer (GC). A total of 756 GC patients were included in this study. Nine SNPs (TLR2: rs3804100, rs7696323, and rs10116253; TLR4: rs10983755, rs11536878, rs1927914, and rs7873784; TLR5: rs5744174; and TLR9: rs187084) in TLR genes were genotyped by MassARRAY assay. Kaplan-Meier survival curves and Cox regression were employed to conduct the associations between SNPs in TLRs and the survival of GC. Multivariate Cox regression indicated that patients with the TLR2 rs3804100 TT genotype exhibited worse survival than those with the CC + CT genotype (HR = 1.262, 95% CI: 1.006–1.582). No significant interaction between rs3804100 and H. pylori infection was observed for the prognosis of GC. Our results suggested that the TLR2 rs3804100 polymorphism may be a potential prognostic biomarker for GC independent of the H. pylori infection-related pathway.     

Elevated levels of adaption in Helicobacter pylori genomes from Japan; a link to higher incidences of gastric cancer?

Helicobacter pylori is a bacterium that lives in the human stomach and is a major risk factor for gastric cancer and ulcers. H.pylori is host dependent and has been carried with human populations around the world after their departure from Africa. We wished to investigate how H.pylori has coevolved with its host during that time, focusing on strains from Japanese and European populations, given that gastric cancer incidence is high in Japanese populations, while low in European. A positive selection analysis of eight H.pylori genomes was conducted, using maximum likelihood based pairwise comparisons in order to maximize the number of strain-specific genes included in the study. Using the genic Ka/Ks ratio, comparisons of four Japanese H.pylori genomes suggests 25–34 genes under positive selection, while four European H.pylori genomes suggests 16–21 genes; few of the genes identified were in common between lineages. Of the identified genes which were annotated, 38% possessed homologs associated with pathogenicity and / or host adaptation, consistent with their involvement in a coevolutionary ‘arms race’ with the host. Given the efficacy of identifying host interaction factors de novo, in the absence of functionally annotated homologs our evolutionary approach may have value in identifying novel genes which H.pylori employs to interact with the human gut environment. In addition, the larger number of genes inferred as being under positive selection in Japanese strains compared to European implies a stronger overall adaptive pressure, potentially resulting from an elevated immune response which may be linked to increased inflammation, an initial stage in the development of gastric cancer.     

Systemic immunization with an epitope-based vaccine elicits a Th1-biased response and provides protection against Helicobacter pylori in mice

Vaccine-mediated Th1-biased CD4+ T cell responses have been shown to be crucial for protection against Helicobacter pylori (H. pylori). In this study, we investigated whether a vaccine composed of CD4+ T cell epitopes together with Th1 adjuvants could confer protection against H. pylori in a mouse model. We constructed an epitope-based vaccine, designated Epivac, which was composed of predicted immunodominant CD4+ T cell epitopes from H. pylori adhesin A (HpaA), urease B (UreB) and cytotoxin-associated gene A product (CagA). Together with four different Th1 adjuvants, Epivac was administered subcutaneously and the prophylactic potential was examined. Compared to non-immunized mice, immunization with Epivac alone or with a Th1 adjuvant significantly reduced H. pylori colonization, and better protection was observed when an adjuvant was used. Immunized mice exhibited a strong local and systemic Th1-biased immune response, which may contribute to the inhibition of H. pylori colonization. Though a significant specific antibody response was induced by the vaccine, no correlation was found between the intensity of the humoral response and the protective effect. Our results suggest that a vaccine containing CD4+ T cell epitopes is a promising candidate for protection against H. pylori infection.     

Plasma ghrelin isoforms and gastric ghrelin O-acyltransferase expression are influenced by Helicobacter pylori status

ObjectiveHelicobacter pylori is known to affect the host’s nutritional status. This study was performed to elucidate the relationship between H. pylori status and the dynamics of the ghrelin system, in the context of ghrelin O-acyltransferase (GOAT) expression.MethodsWe conducted a clinical study of 30 subjects focusing on the following points: 1) the effects of H. pylori infection on the concentrations of circulating ghrelin isoforms and on ghrelin and GOAT mRNA expression in the gastric mucosa, and 2) the effects of H. pylori eradication on the same parameters.ResultsThe plasma acyl-ghrelin and desacyl-ghrelin concentrations of 16 H. pylori positive participants were significantly lower than those of 14 H. pylori negative controls. The acyl-ghrelin/desacyl-ghrelin ratio was not significantly different between the H. pylori positive and H. pylori negative participants. The levels of ghrelin and GOAT mRNA in the gastric mucosa were significantly lower in the H. pylori positive participants than in the H. pylori negative controls. In 11 subjects in whom H. pylori eradication was successful, their plasma acyl-ghrelin levels tended to increase after H. pylori eradication, but the difference was not significant; however, their plasma desacyl-ghrelin levels were significantly reduced. Although gastric ghrelin mRNA expression increased significantly after H. pylori eradication, gastric GOAT mRNA expression tended to increase but was not significantly altered.ConclusionH. pylori status might affect the host’s nutritional status through changes in the plasma levels of ghrelin isoforms and the gastric expression levels of ghrelin and GOAT mRNA.     

Association of Helicobacter pylori infection with estimated glomerular filtration rate in a Chinese population

BackgroundHelicobacter pylori (H. Pylori) infection is reported to be associated with extragastric disorders which include kidney diseases. But the association between H. pylori infection and estimated glomerular filtration rate (eGFR) is unclear as far. Thus, we performed the study to investigate the prevalence of H. pylori infection and its association with eGFR in a Chinese population.Materials and methodsWe conducted a cross-sectional study in adults who took health examination at the First Hospital of Jilin University in 2019. All the subjects received ¹⁴C-labled urea breath test to determine the H. pylori infection, and we analyzed the relationship between prevalence of H. pylori infection and eGFR.ResultsAmong 3593 participants in the health checkup, the positive rate of H. pylori infection was 37.3%. H. pylori-positive participants had a lower level of eGFR than H. pylori-negative participants. In univariate analysis, we observed that the positive rate of H. pylori infection and RR (relative risk) became larger with eGFR decreased, however, the association was not significant after adjustment for other factors. Further multivariable analysis showed age and sex were the main confounders between eGFR and H. pylori infection.ConclusionsThe correlation between eGFR and positive rate of H. pylori infection was confounded by age and sex.     

Helicobacter pylori cagE,cagG, and cagM can be a prognostic marker for intestinal and diffuse gastric cancer

It is known that Helicobacter pylori is the main cause of peptic ulceration and gastric cancer. However, there is a lack of information on whether H. pylori strains may differ in gastric cancer histological subtypes. This study aimed to investigate different H. pylori strains considering six cag Pathogenicity Island - cagPAI genes (cagA, cagE, cagG, cagM, cagT, and virb11), and vacuolating cytotoxin - vacA alleles, and their relation to gastric cancer histologic subtypes. For this purpose, tumor samples from 285 patients with gastric carcinoma were used. H. pylori infection and genotypes were determined by polymerase chain reaction (PCR). H. pylori was detected in 93.9% of gastric tumors. For comparative analyzes between histopathological subtypes considering H. pylori cagPAI genes the strains were grouped according to the vacA s1/s2 alleles. In the vacAs1 group, the strains cagA(−)cagE(+), cagA(+)cagE(+)cagG(+), cagA(+)cagM(+), or only cagE(+) strains were more frequent in the intestinal subtype (P = .009; P = .024; P = .046, respectively). In contrast, cagM(+)cagG(+)cagA(−) and cagE(−) were associated with diffuse tumors (P = .036), highlighting the presence of cagE in the development of intestinal tumors, and the presence of cagG and absence of cagE in diffuse tumors. Furthermore, WEKA software and Decision Tree (CART) analyses confirmed these findings, in which cagE presence was associated with intestinal tumors, and cagE absence and cagG(+) with diffuse tumors. In conclusion our results showed that vacAs1 (cagG + cagM) strains, mainly cagG positive with cagE absence, were relevant in the studied population for the diffuse outcome, while the presence of cagE was relevant for the intestinal outcome. These findings suggest the relevance of these H. pylori genes as potential markers for gastric cancer histological outcomes.     

The natural course of Helicobacter pylori infection on endoscopic findings in a population during 17 years of follow-up: the Sørreisa gastrointestinal disorder study

The natural course of Helicobacter pylori (H. pylori) is poorly understood, as most research in the field has been on patient populations. We studied the natural course of H. pylori and its associations to morphological changes of the gastric mucosa, peptic ulcer, and reflux oesophagitis in a prospective cohort study of subjects with and without dyspepsia. A total of 361 adults (201 men/160 women, mean age 41/42 years) in Sørreisa municipality, Norway who in 1987 were subjected to upper endoscopy and assessed for gastrointestinal symptoms and H. pylori status were followed up in 2004. H. pylori was strongly associated with neutrophilic (odds ratio [OR] 23.79; 95% confidence interval [CI] 11.64:48.61) and mononuclear infiltration (OR 9.43; CI 5.12:17.36), moderately with atrophy of the antrum (OR 1.98; CI 1.17:3.34), but not with atrophy of the gastric body or intestinal metaplasia. Elimination of H. pylori was associated with regression of gastric inflammation and atrophy, whereas intestinal metaplasia progressed. H. pylori was positively associated with peptic ulcer (OR 2.69; CI 1.2:6.02) but not significantly negatively associated with oesophagitis (OR 0.62; CI 0.35:1.09). This is the first prospective study including endoscopic findings of subjects without dyspepsia, to show that the impact of H. pylori on gastric atrophy is only modest, and that eliminating H. pylori does not cause regression of intestinal metaplasia. However, inflammation of the gastric mucosa regresses after H. pylori elimination. H. pylori is only a moderate risk factor for peptic ulcer, and other explanatory factors deserve more attention.     

HelicoVax: epitope-based therapeutic Helicobacter pylori vaccination in a mouse model

Helicobacter pylori is the leading cause of gastritis, peptic ulcer disease and gastric adenocarcinoma and lymphoma in humans. Due to the decreasing efficacy of anti-H. pylori antibiotic therapy in clinical practice, there is renewed interest in the development of anti-H. pylori vaccines. In this study an in silico-based approach was utilized to develop a multi-epitope DNA-prime/peptide-boost immunization strategy using informatics tools. The efficacy of this construct was then assessed as a therapeutic vaccine in a mouse model of gastric cancer induced by chronic H. pylori infection. The multi-epitope vaccine administered intranasally induced a broad immune response as determined by interferon-gamma production in ELISpot assays. This was associated with a significant reduction in H. pylori colonization compared with mice immunized with the same vaccine intramuscularly, given an empty plasmid, or given a whole H. pylori lysate intranasally as the immunogen. Total scores of gastric histological changes were not significantly different among the 4 experimental groups. These results suggest that further development of an epitope-based mucosal vaccine may be beneficial in eradicating H. pylori and reducing the burden of the associated gastric diseases in humans.