Peroral immunization with Helicobacter pylori adhesin protein genetically linked to cholera toxin A2B subunits

2001 ◽  
Vol 100 (3) ◽  
pp. 291-298 ◽  
Author(s):  
Byung Oh KIM ◽  
Sung Seup SHIN ◽  
Young Hyo YOO ◽  
Suhkneung PYO
Keyword(s):  
Helicobacter Pylori ◽  
Cholera Toxin ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Oral Immunization ◽  
Size Exclusion ◽  
Vaccine Antigen ◽  
Igg Antibodies ◽  
Serum Igg ◽  
H Pylori

Helicobacter pylori is a major cause of gastric-associated diseases. To evaluate the efficacy of a possible vaccine antigen against H. pylori infection, the chimaeric construct adhesin–CTXA2B, derived from H. pylori adhesin genetically coupled to cholera toxin (CTX) subunits A2 and B (CTXA2B), was expressed in Escherichia coli as an insoluble recombinant chimaeric protein. The protein was then purified by denaturation, renaturation and size-exclusion chromatography. The composition of purified adhesin–CTXA2B was verified by SDS/PAGE and Western blotting with antibodies to antigenic components of adhesin and CTXB, and confirmed as a chimaeric protein with GM1-ganglioside binding activity and adhesin epitopes by a GM1-ELISA developed using antibodies to adhesin. Oral immunization of mice with adhesin–CTXA2B induced higher levels of mucosal IgA and serum IgG antibodies to H. pylori adhesin and to CTXB than in mice immunized with adhesin or CTXA2B alone. Adhesin–CTXA2B was also demonstrated to be a potential protective antigen in a mouse model of H. pylori infection. The immunization of mice with adhesin–CTXA2B protected 62.5% of mice infected with H. pylori SS1 strain, whereas adhesin immunization was not able to confer protection to mice. This protection may be correlated with high levels of mucosal IgA and serum IgG antibodies against H. pylori adhesin. Taken together, the results indicate that the genetically linked CTXA2B acts as a useful mucosal adjuvant, and that the adhesin–CTXA2B chimaeric protein could be a potential component in future H. pylori vaccine development.

scholarly journals Effects of Oral Vaccination and Immunomodulation by Cholera Toxin on Experimental Helicobacter pylori Infection, Reinfection, and Gastritis

2002 ◽  
Vol 70 (8) ◽  
pp. 4621-4627 ◽  
Author(s):  
S. Raghavan ◽  
A.-M. Svennerholm ◽  
J. Holmgren
Keyword(s):  
Helicobacter Pylori ◽  
Cholera Toxin ◽  
Mononuclear Cells ◽  
Oral Treatment ◽  
Bacterial Load ◽  
Oral Immunization ◽  
Initial Infection ◽  
Fold Reduction ◽  
H Pylori

ABSTRACT Therapeutic vaccination is an attractive strategy to control infection and disease caused by Helicobacter pylori. In mice infected with H. pylori we have studied the protective effect of oral immunization with an H. pylori lysate preparation given together with the mucosal adjuvant cholera toxin (CT), both against the initial infection and against a later reinfection challenge. We have also examined the effects of treatment with the CT adjuvant alone on H. pylori infection and reinfection. Specific immunization with lysate was found to result in a sixfold reduction of the extent (bacterial load) of the primary infection and also to provide similar levels of protection against reinfection. However, these effects were associated with severe postimmunization gastritis. In contrast, oral treatment with CT alone at the time of initial infection, while unable to suppress the initial infection, gave rise to a 20-fold reduction in bacterial load upon reinfection without causing any associated gastric inflammation. Both the infected animals that were specifically immunized and those that were treated with CT only displayed increased in vitro proliferative responses of mononuclear cells to H. pylori antigens. Antibody levels in response to H. pylori were on the other hand only marginally increased after treatment with CT, whereas they were markedly elevated after immunization with lysate plus CT, with a rise in both (Th2-driven) immunoglobulin G1 (IgG1) and, especially, (Th1-driven) IgG2a antibodies. The results illustrate the complex balance between protection and harmful inflammation after postinfection vaccination against H. pylori as studied in a mouse model.

scholarly journals Pre-existing Helicobacter pylori serum IgG enhances the vibriocidal antibody response to CVD 103-HgR live oral cholera vaccine in Malian adults

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Khitam Muhsen ◽  
Samba O. Sow ◽  
Milagritos D. Tapia ◽  
Fadima C. Haidara ◽  
Mardi Reymann ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Oral Vaccine ◽  
Adjusted Relative Risk ◽  
Cholera Vaccine ◽  
Igg Antibodies ◽  
Fourfold Increase ◽  
Serum Igg ◽  
Serum Pepsinogens ◽  
Oral Cholera Vaccine ◽  
H Pylori

Abstract Accumulating evidence indicates that persistent Helicobacter pylori gastric infection influences immune responses to oral enteric vaccines. We studied the association between pre-existing H. pylori serum IgG and serum pepsinogens levels (PGs) as markers of gastric inflammation and the immune response to single-dose live oral cholera vaccine CVD 103-HgR in Malian adults. Baseline sera obtained during a phase 2 safety/immunogenicity clinical trial of cholera vaccine CVD 103-HgR among 93 healthy Malian adults were tested for H. pylori IgG antibodies and PGI and PGII levels using enzyme linked immunosorbent assays. Overall 74/93 (80%) vaccine recipients were H. pylori IgG seropositive at baseline. Vibriocidal antibody seroconversion (≥ fourfold increase 14 days following administration of CVD 103-HgR compared to baseline) among vaccine recipients was 56%. However, vibriocidal antibody seroconversion was markedly higher among H. pylori seropositives than seronegatives 64% vs. 26% (p = 0.004); adjusted relative risk: 2.20 (95% confidence intervals 1.00–4.80; p = 0.049). Among H. pylori seropositive vaccine recipients, there were no significant associations between PGI, PGII and PGI:PGII levels and vibriocidal seroconversion. The enhanced seroconversion to oral cholera vaccine CVD 103-HgR among H. pylori seropositive African adults provides further evidence of the immunomodulating impact of H. pylori on oral vaccine immunogenicity.

scholarly journals Protection against Experimental Helicobacter pylori Infection after Immunization with Inactivated H. pylori Whole-Cell Vaccines

2002 ◽  
Vol 70 (11) ◽  
pp. 6383-6388 ◽  
Author(s):  
S. Raghavan ◽  
M. Hjulström ◽  
J. Holmgren ◽  
A.-M. Svennerholm
Keyword(s):  
Helicobacter Pylori ◽  
Protective Effect ◽  
Cholera Toxin ◽  
Oral Immunization ◽  
Helicobacter Pylori Infection ◽  
The Other ◽  
Whole Cell ◽  
O Antigen ◽  
Lewis Antigen ◽  
H Pylori

ABSTRACT The protective effect of therapeutic oral immunization with homologous and heterologous formalin-inactivated Helicobacter pylori cells given together with cholera toxin as an adjuvant was evaluated with C57BL/6 mice infected with H. pylori Sydney strain 1 (SS1). The bacteria used for immunization were strains that were either homologous or heterologous with regard to the O antigen (i.e., the Lewis antigen [Le antigen]) expressed by the lipopolysaccharide of the infecting H. pylori SS1 strain. We found that repeated oral immunization with inactivated H. pylori SS1 cells can significantly inhibit an existing infection (P < 0.001) and that the protection induced by such therapeutic immunization extends to protection against reinfection (P < 0.001). A similar level of protection was also achieved by immunization with another inactivated H. pylori strain having the same O antigen (Le antigen) as the infecting H. pylori SS1 strain. In contrast, immunization with inactivated strains expressing a heterologous O antigen, Lex, provided less protection or no protection. Immunization with H. pylori lysate preparations, on the other hand, resulted in significant comparable protection whether the lysates were prepared from an Lex strain or an Ley strain. Postimmunization gastritis was seen in mice that were protected after vaccination but not in unimmunized or unprotected mice. In conclusion, therapeutic immunization with inactivated H. pylori whole-cell vaccines may provide strong protection both against experimental H. pylori infection and against later reinfection.

scholarly journals The Neutrophil-Activating Protein (Hp-Nap) of Helicobacter pylori Is a Protective Antigen and a Major Virulence Factor

2000 ◽  
Vol 191 (9) ◽  
pp. 1467-1476 ◽  
Author(s):  
Barbara Satin ◽  
Giuseppe Del Giudice ◽  
Vittorina Della Bianca ◽  
Stefano Dusi ◽  
Carlo Laudanna ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Virulence Factor ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Cytosolic Calcium ◽  
Interferon Γ ◽  
Human Gastric Mucosa ◽  
Oxygen Intermediates ◽  
H Pylori ◽  
Factor Α

Helicobacter pylori infection induces the appearance of inflammatory infiltrates, consisting mainly of neutrophils and monocytes, in the human gastric mucosa. A bacterial protein with neutrophil activating activity (HP-NAP) has been previously identified, but its role in infection and immune response is still largely unknown. Here, we show that vaccination of mice with HP-NAP induces protection against H. pylori challenge, and that the majority of infected patients produce antibodies specific for HP-NAP, suggesting an important role of this factor in immunity. We also show that HP-NAP is chemotactic for human leukocytes and that it activates their NADPH oxidase to produce reactive oxygen intermediates, as demonstrated by the translocation of its cytosolic subunits to the plasma membrane, and by the lack of activity on chronic granulomatous disease leukocytes. This stimulating effect is strongly potentiated by tumor necrosis factor α and interferon γ and is mediated by a rapid increase of the cytosolic calcium concentration. The activation of leukocytes induced by HP-NAP is completely inhibited by pertussis toxin, wortmannin, and PP1. On the basis of these results, we conclude that HP-NAP is a virulence factor important for the H. pylori pathogenic effects at the site of infection and a candidate antigen for vaccine development.

A multi-method and structure-based in silico vaccine designing against Helicobacter pylori employing immuno-informatics approach

2020 ◽  
Vol 17 ◽  
Author(s):  
Anam Naz ◽  
Tahreem Zaheer ◽  
Hamza Arshad Dar ◽  
Faryal Mehwish Awan ◽  
Ayesha Obaid ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Vaccine Development ◽  
Amino Acid Sequences ◽  
The Body ◽  
New Drugs ◽  
Toll Like Receptor ◽  
Peptide Vaccines ◽  
Hla Alleles ◽  
Vaccine Candidates ◽  
H Pylori

Background: Helicobacter pylori infection and its treatment still remains a challenge to human health worldwide. A variety of antibiotics and combination therapies are currently used to treat H. pylori induced ulcers and carcinoma; however, no effective treatment is available to eliminate the pathogen from the body. Additionally, antibiotic resistance is also one of the main reasons for prolonged and persistent infection. Aim of the study: Until new drugs are available for this infection, vaccinology seems the only alternative opportunity to exploit against H. pylori induced diseases. Methods: Multiple epitopes prioritized in our previous study have been tested for their possible antigenic combinations, and results in 169-mer and 183-mer peptide vaccines containing the amino acid sequences of 3 and 4 epitopes respectively, along with adjuvant (Cholera Toxin Subunit B adjuvant at 5’ end) and linkers (GPGPG and EAAAK). Results: Poly-epitope proteins proposed as potential vaccine candidates against H. pylori include SabAHP0289-Omp16-VacA (SHOV), VacA-Omp16-HP0289-FecA (VOHF), VacA-Omp16-HP0289-SabA (VOHS), VacA-Omp16-HP0289-BabA (VOHB), VacA-Omp16-HP0289-SabA-FecA (VOHSF), VacAOmp16-HP0289-SabA-BabA (VOHSB) and VacA-Omp16-HP0289-BabA-SabA (VOHBS). Structures of these poly-epitope peptide vaccines have been modelled and checked for their affinity with HLA alleles and receptors. These proposed poly-epitope vaccine candidates bind efficiently with A2, A3, B7 and DR1 superfamilies of HLA alleles. They can also form stable and significant interactions with Toll-like receptor 2 and Toll-like receptor 4. Conclusion: Results suggest that these multi-epitopic vaccines can elicit a significant immune response against H. pylori and can be tested further for efficient vaccine development.

scholarly journals Study on Association between Chronic Idiopathic Urticaria and Helicobacter Pylori Infection in Armed Forces Personnel

2016 ◽  
Vol 12 (2) ◽  
pp. 122-126 ◽  
Author(s):  
Md Sayeed Hasan ◽  
Md Shirajul Islam Khan ◽  
Jannatun Nayeem
Keyword(s):  
Helicobacter Pylori ◽  
Eradication Therapy ◽  
Armed Forces ◽  
Case Control ◽  
Chronic Idiopathic Urticaria ◽  
Helicobacter Pylori Infection ◽  
Enteric Infection ◽  
Clinical Disorder ◽  
Serum Igg ◽  
H Pylori

Introduction: Chronic Idiopathic Urticaria (CIU) has an estimated prevalence of 35-65% and impacts 15 to 25% of the population at some point in their lives. Studies have shown the possible involvement of Helicobacter pylori (H. pylori) infection in chronic idiopathic urticaria (CIU), but the relationship remains controversial. Objective: To quantitatively assess the association between H. pylori infection and chronic idiopathic urticaria. Materials and Methods: This was a case-control type of analytical study and 100 patients were enrolled fifty patients of CIU fulfilling inclusion criteria with no identifiable cause were taken as case and patients without urticaria were taken as control, attending in the department of Dermatology & Venereology, CMH Dhaka for treatment from May 2015 to Aug 2016. Helicobacter pylori infection was confirmed by serum IgG for H. pylori test. Results: The result showed that H. pylori infection significantly affected a high percentage of patients 30 (60%) with chronic idiopathic urticaria. Male respondents were more positive 16(53.3%) than female 14(46.7%), in the middle aged 31-50 year about 18(60%) and triple drug therapy was successful in 16(53.33%) patients in whom H. pylori was detected. Conclusion: Urticaria is a common clinical disorder with complex triggering factors. Chronic urticaria has provided evidence that enteric infection with H. pylori may induce the disease. In this case control study, it was evident that chronic idiopathic urticaria was associated with positive serum IgG for H. Pylori. A trial of H. pylori eradication therapy may be offered to patients with CIU and evidence of H. pylori infection. Journal of Armed Forces Medical College Bangladesh Vol.12(2) 2016: 122-126

scholarly journals Preliminary Serological Study of Helicobacter pylori Infection in Some University Students

2020 ◽  
Vol 6 ◽  
pp. 1
Author(s):  
Abdullah A Mahrazi ◽  
Mohammad A Khibrani ◽  
Khatib S Ismail ◽  
Emad Abada ◽  
◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
University Students ◽  
Large Scale ◽  
Confirmatory Test ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Collection ◽  
Igg Antibodies ◽  
Igm Antibodies ◽  
H Pylori

Helicobacter pylori has been associated with peptic ulcer and gastric carcinoma. This study aimed to find the seroprevalence of H. pylori infection in some male students of Jazan University, Saudi Arabia. Twenty students were enrolled in the study (n = 20). Informed consent was obtained from the students. About 2 ml blood was collected intravenously in Improvacuter® evacuated blood collection tubes. The blood was allowed to clot at room temperature. The serum was collected and stored at –20°C for further use. The separated serum was used to detect IgG and IgM antibodies by Enzyme Linked Immunosorbent Assay (ELISA) against H. pylori for the in vitro diagnosis. A total of 11 (55.00%) students tested positive for IgG antibodies against H. pylori indicating previous infection. All the samples tested negative for IgM antibodies against H. pylori indicating no active infection. The seroprevalance of IgG antibodies against H. pylori was found to be very high in some male university students and is a cause of concern regarding their health. Obesity (p < 0.05; Value statistically significant), stress and bad eating habits, eating out, drinking carbonated beverages, and eating spicy food were some of the factors found to be associated with IgG seropositive students. The students were counseled and were instructed to undergo a confirmatory test and get medical intervention. Further large-scale studies need to be performed to plan action against this disease causing organism and to improve the health of students.

scholarly journals The Patterns and Associated Cost of Serologic Testing for Helicobacter pylori in the U.S. Military Health System

2020 ◽  
Vol 185 (9-10) ◽  
pp. e1417-e1419
Author(s):  
Kevin Pak ◽  
Zachary Junga ◽  
Andrew Mertz ◽  
Manish Singla
Keyword(s):  
Helicobacter Pylori ◽  
Clinical Utility ◽  
Igg Antibodies ◽  
Military Health System ◽  
Military Health ◽  
Igm Antibodies ◽  
Serologic Testing ◽  
Stool Antigen ◽  
H Pylori ◽  
The U.S

Abstract Introduction Helicobacter pylori (H. pylori) infection affects about half of the world’s population and can lead to multiple complications if left untreated. Testing for H. pylori infection in appropriate patients with prompt treatment followed by the testing of eradication is the standard of care in the United States. Active Duty Service members (ADSMs) in the U.S. military are a unique patient population that may be at higher risk for acquiring H. pylori infection given frequent deployments to developing countries. Noninvasive diagnostic strategies include the urea breath test, the stool antigen test, and serologic testing, which include H. pylori immunoglobulin M (IgM), immunoglobulin A (IgA), and immunoglobulin G (IgG) antibodies. Among noninvasive methods, the least sensitive is serology, and although there is clinical utility in testing for H. pylori IgG antibodies, H. pylori IgA or IgM antibodies have limited clinical utility. Despite this, H. pylori IgA and IgM antibodies are still widely ordered across the Military Health System. Materials and Methods In order to determine how frequently this testing is being ordered and the associated cost, we conducted a retrospective cross-sectional study of H. pylori serologic testing utilization in the MHS from October 2015 to September 2018 in adult patients using the MHS Data Repository. All H. pylori IgM, IgA, and IgG antibodies, H. pylori stool antigen tests, and H. pylori urea breath tests were queried during this time period across all ADSMs, retirees, and ADSM dependents for all adults. Cost information was obtained from LabCorp, and the institutional price used for cost analysis was the same throughout all military treatment facilities in the Department of Defense (DOD). Results We discovered that over a 3-yr period, 1,916 H. pylori IgA and 2,492 IgM antibodies were ordered. In total, the DOD spent close to $400,000 on antibody-based testing for H. pylori not accounting for indirect associated costs like personnel, supplies, repeat testing, as well as the costs of delayed diagnosis and associated complications. Conclusion H. pylori IgM and IgA have limited clinical utility, are inaccurate, and are costly to maintain, especially when more accurate alternative tests are available. Based on our analysis, we strongly recommend the removal of the H. pylori IgA and IgM serologic tests throughout the DOD in order to improve the efficiency and quality of care for patients suspected of having an H. pylori infection. Further research is needed to determine how these tests are ordered, how providers are responding to the results of the serologic tests, and if noninvasive testing is being ordered appropriately.

Noninvasive evaluation of Helicobacter pylori therapy: role of fasting or postprandial gastrin, Pepsinogen I, Pepsinogen II, or serum IgG antibodies

1999 ◽  
Vol 94 (9) ◽  
pp. 2367-2372 ◽  
Author(s):  
M. Tarek Al-Assi ◽  
Kazumasa Miki ◽  
John H. Walsh ◽  
David P. Graham ◽  
Masahiro Asaka ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Noninvasive Evaluation ◽  
Igg Antibodies ◽  
Pepsinogen I ◽  
Serum Igg ◽  
Pepsinogen Ii

scholarly journals Correlates of infection with Helicobacter pylori positive and negative cytotoxin-associated gene A phenotypes among Arab and Jewish residents of Jerusalem

2019 ◽  
Vol 147 ◽  
Author(s):  
K. Muhsen ◽  
R. Sinnereich ◽  
G. Beer-Davidson ◽  
H. Nassar ◽  
W. Abu Ahmed ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Former Soviet Union ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibodies ◽  
Multinomial Regression ◽  
Igg Antibody ◽  
Sibship Size ◽  
Cross Sectional ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

Abstract We examined the prevalence and correlates of Helicobacter pylori (H. pylori) infection according to cytotoxin-associated gene A (CagA) phenotype, a main virulence antigen, among the ethnically diverse population groups of Jerusalem. A cross-sectional study was undertaken in Arab (N = 959) and Jewish (N = 692) adults, randomly selected from Israel's national population registry in age-sex and population strata. Sera were tested for H. pylori immunoglobulin G (IgG) antibodies. Positive samples were tested for virulence IgG antibodies to recombinant CagA protein, by enzyme-linked immunosorbent assay. Multinomial regression models were fitted to examine associations of sociodemographic factors with H. pylori phenotypes. H. pylori IgG antibody sero-prevalence was 83.3% (95% confidence interval (CI) 80.0%–85.5%) and 61.4% (95% CI 57.7%–65.0%) among Arabs and Jews, respectively. Among H. pylori positives, the respective CagA IgG antibody sero-positivity was 42.3% (95% CI 38.9%–45.8%) and 32.5% (95% CI 28.2%–37.1%). Among Jews, being born in the Former Soviet Union, the Middle East and North Africa, vs. Israel and the Americas, was positively associated with CagA sero-positivity. In both populations, sibship size was positively associated with both CagA positive and negative phenotypes; and education was inversely associated. In conclusion, CagA positive and negative infection had similar correlates, suggesting shared sources of these two H. pylori phenotypes.

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