title: A novel design of a multi-antigenic, multistage and multi-epitope vaccine against Helicobacter pylori: An in silico approach.
abstract: Helicobacter pylori have colonized the gastric mucosa of half of the population worldwide. This bacterium is classified as a definitive type I carcinogen by the World Health Organization and no effective vaccine has been found against it yet. Thus, a logical and rational vaccine design against H. pylori is necessary. Because of its tremendous complexity and elicited immune responses, the vaccine design should considered multiple antigens to enhance immune-protection, involved in the different stages of pathogenesis besides inducing a specific immune response by B- and T-cell multi-epitopes. In this study, emphasis was placed on the design of a new unique vaccine named CTB-multiHp. In silico techniques were used to design a chimeric construct consisting of cholera toxin B subunit fused to multi-epitope of urease B (residue 148-158, 188-198), cytotoxin-associated gene A (residue 584-602), neutrophil activating protein (residue 4-28), vacuolating cytotoxin gene A (residue 63-81), H. pylori adhesine A (residue77-99), heat shock protein A (residue 32-54) and gamma glutamyl transpeptidase (residue 271-293). The tertiary structure and features of the vaccine were analyzed. The chimeric protein was expressed in Escherichia coli BL21 and the serology analyses indicated that the CTB-multiHp protein produced exhibit immune-reactivity. The results showed that CTB-multiHp could be a good vaccine candidate against H. pylori. Ongoing studies will evaluate the effects of CTB-multiHp against H. pylori infection.
authors.affiliation: Grupo de Inmunología & Vacunología, Centro de Investigaciones Biológicas del Noroeste, La Paz, B.C.S., Mexico; Laboratorio de Patogénesis Microbiana, Centro de Investigaciones Biológicas del Noroeste, La Paz, B.C.S., Mexico. Electronic address: mezamarquezbeatriz@gmail.com.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Meza
authors.affiliation: Laboratorio de Patogénesis Microbiana, Centro de Investigaciones Biológicas del Noroeste, La Paz, B.C.S., Mexico. Electronic address: ascencio@cibnor.mx.
authors.forename: Felipe
authors.initials: F
authors.lastname: Ascencio
authors.affiliation: Laboratorio de Proteómica, Centro de Investigaciones Biológicas del Noroeste, La Paz, B.C.S., Mexico. Electronic address: asierra04@cibnor.mx.
authors.forename: Arturo Pedro
authors.initials: AP
authors.lastname: Sierra-Beltrán
authors.affiliation: Unidad de Investigación en Enfermedades Infecciosas, Hospital de Pediatría, Centro Médico Nacional Siglo-XXI, Instituto Mexicano del Seguro Social, Ciudad de México, Mexico. Electronic address: jtorresl57@yahoo.com.mx.
authors.forename: Javier
authors.initials: J
authors.lastname: Torres
authors.affiliation: Grupo de Inmunología & Vacunología, Centro de Investigaciones Biológicas del Noroeste, La Paz, B.C.S., Mexico. Electronic address: eangulo@cibnor.mx.
authors.forename: Carlos
authors.initials: C
authors.lastname: Angulo
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001428:Bacterial Vaccines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D002772:Cholera Toxin / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D003001:Cloning, Molecular; D015195:Drug Design; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D014510:Urease / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D005723:gamma-Glutamyltransferase / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D000939:Epitopes; D006360:Heat-Shock Proteins; C113725:HspA protein, bacteria; D016209:Interleukin-8; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C074689:VacA protein, Helicobacter pylori; C080866:cagA protein, Helicobacter pylori; D002772:Cholera Toxin; D005723:gamma-Glutamyltransferase; D014510:Urease
keywords: Helicobacter pylori; In silico; Multi-antigenic; Multi-epitope; Multistage; Vaccine design