title: Enhanced mucosal and systemic immune responses to Helicobacter pylori antigens through mucosal priming followed by systemic boosting immunizations.
abstract: It is estimated that Helicobacter pylori infects the stomachs of over 50% of the world's population and if not treated may cause chronic gastritis, peptic ulcer disease, gastric adenocarcinoma and gastric B-cell lymphoma. The aim of this study was to enhance the mucosal and systemic immune responses against the H. pylori antigens cytotoxin-associated gene A (CagA) and neutrophil-activating protein (NAP), through combinations of mucosal and systemic immunizations in female BALB/c mice. We found that oral or intranasal (i.n.) followed by i.m. immunizations induced significantly higher serum titres against NAP and CagA compared to i.n. alone, oral alone, i.m. alone, i.m. followed by i.n. or i.m. followed by oral immunizations. However, only oral followed by i.m. immunizations induced anti-NAP antibody-secreting cells in the stomach. Moreover, mucosal immunizations alone or in combination with i.m., but not i.m. immunizations alone, induced mucosal immunoglobulin A (IgA) responses in faeces. Any single route or combination of immunization routes with NAP and CagA preferentially induced antigen-specific splenic interleukin-4-secreting cells and far fewer interferon-gamma-secreting cells in the spleen. Moreover, i.n. immunizations alone or in combination with i.m. immunizations induced predominantly serum IgG1 and far less serum IgG2a. Importantly, we found that while both i.n. and i.m. recall immunizations induced similar levels of serum antibody responses, mucosal IgA responses in faeces were only achieved through i.n. recall immunization. Collectively, our data show that mucosal followed by systemic immunization significantly enhanced local and systemic immune responses and that i.n. recall immunization is required to induce both mucosal and systemic memory type responses.
authors.affiliation: Immunology and Infectious Diseases, Emeryville, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Vajdy
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Mildred
authors.initials: M
authors.lastname: Ugozzoli
authors.forename: Maylene
authors.initials: M
authors.lastname: Briones
authors.forename: Elawati
authors.initials: E
authors.lastname: Soenawan
authors.forename: Lina
authors.initials: L
authors.lastname: Cuadra
authors.forename: Jina
authors.initials: J
authors.lastname: Kazzaz
authors.forename: Paolo
authors.initials: P
authors.lastname: Ruggiero
authors.forename: Samuele
authors.initials: S
authors.lastname: Peppoloni
authors.forename: Francesco
authors.initials: F
authors.lastname: Norelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: del Giudice
authors.forename: Derek
authors.initials: D
authors.lastname: O'Hagan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016480:Helicobacter pylori / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines