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Analysis Of Polymorphism And Physiochemical Characteristics Of Flagellin A And Identification Of A B-cell Epitope In Helicobacter Pylori

Posted on:2003-02-08Degree:DoctorType:Dissertation
Country:ChinaCandidate:W S JiFull Text:PDF
GTID:1104360062490743Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background Helicobacter pylorus (H.pylorus) was a spiral Gram-negative bacterium, discovered by Australian doctor Marshall and Warren in 1982. The discovery of this worm was made one of the great milestones in the history of current gastroenterology. More than half of the population was infected by H. pylori all over the world. Actually, the occurrence was lower in occidental developed countries than that in developing countries. Up to date, Hp infection was accepted as the major pathogenic factor of chronic active gastritis and peptic ulcers; it was related to the occurrence of atrophic gastritis, intestinal epithelial metaplasia, gastric polypi and mucosal associate lymphoid tissue lymphoma(MALT). Generally, infection of Hp was related to the occurrence of gastric adenocarcinoma, and it was listed by WHO as one of the class I carcinogenic factors in 1994. Eradication of H. pylori relieved part of clinical symptoms, reduced the recurrence of duodenal ulcers and might cure some cases of slightly malignant MALT lymphoma and gastric proliferative polypi. Although significant progress had been made in treating H. pylori infection with current triple or quadruple therapy based on antibiotics, given in conjunction with bismuth compounds and proton pump inhibitors, the limitations of pharmacological therapy such as the side effects, the poor compliance, the lower ratio of effect to cost, and most importantly, the rapid emergence of antibiotic resistance had set the stage for the development of less costly and more efficient means to prevent and control H. pylori infections. There was sufficient evidence suggesting that vaccination may be such an alternative. It is widely accepted that, given the worldwide prevalence of Helicobacter infection and the difficulties inherent hi trying to eradicate it by antibiotics, vaccination would be a preferable strategy. Both prophylactic and therapeutic efficiency could be achieved in animal models, which suggested that the immune response in natural infection be different from that induced by immunization. Though the mechanism to achieve effective protection was still unknown, it was accepted currently that regulativeCD4+ T lymphocyte played a key role in successful immunization. In United States, a model study showed that 580 million dollars was spared if the current treatment was replaced by vaccine therapy and prevention. In our country, the occurrence of Hp infection and gastric carcinoma was higher than the occidental developed countries, which made vaccine therapy and prevention in large population more valuable in both theory and clinical practice.Urease subunit B, heat shock protein60 (Hsp60), CagA and IceA were the main molecular candidates for vaccine design against Hp. Adjuvant and/or carrier included cholera toxin, E. coli heat labile toxin, or their improved form; complete Freund Adjuvant, CFA) /IFA (Incomplete Freund Adjuvant, IFAX some attenuated Salmonella strains and so on. Though partial or complete clearance of Hp was observed in many animal models, the efficiency was doubtful in clinical research. The few alternatives of molecular targets and the side effects of adjuvants were two bottlenecks limiting the further research on Hp vaccine. Therefore, it was essential to explore new molecular targets and new types of vaccine, and synthesized polypeptide was one of the ideal alternatives. Advantages of synthesized polypeptide were shown in many aspects. Non-specific immune response was reduced so as to obtain a clear background, which is very important in research; with the development of synthetic technique, it was very simple and operable to get the polypeptides that attained to the required quantity and purity; it was convenient to regulate the required type of immune response; and the side effects were reduced due to the simple backgroud of synthesized polypeptide.AIM In these experiments, polymorphism and physiochemical characters of Flagellin A were analyzed by soft wares to predict and identify the B-cell epitopes in this molecule. Results here mig...
Keywords/Search Tags:Helicobacter pylori, Flagellin A, Polymorphism, physiochemical character, Antigenic analysis, B-cell epitope, Vaccine
PDF Full Text Request
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