title: Effectiveness of vaccination with recombinant HpaA from Helicobacter pylori is influenced by host genetic background.
abstract: Several studies have explored the production and immunogenicity of HpaA as a potential protective antigen against Helicobacter pylori but little is known regarding its protective capabilities. We therefore evaluated the protective efficacy of recombinant HpaA (rHpaA) as a candidate vaccine antigen against H. pylori. To explore the impact of genetic diversity, inbred and outbred mice were prophylactically and therapeutically immunized with rHpaA adjuvanted with cholera toxin (CT). Prophylactic immunization induced a reduction in bacterial colonization in BALB/c and QS mice, but was ineffective in C57BL/6 mice, despite induction of antigen-specific antibodies. By contrast, therapeutic immunization was effective in all three strains of mice. Prophylactic immunization with CT-adjuvanted rHpaA was more effective when delivered via the nasal route than following intragastric delivery in BALB/c mice. However, HpaA-mediated protection was inferior to that induced by bacterial lysate. Hence, protective efficacy is inducible with vaccines containing HpaA, most relevantly shown in an outbred population of mice. The effectiveness of protection induced by HpaA antigen was influenced by host genetics and was less effective than lysate. HpaA therefore has potential for the development of effective immunization against H. pylori but this would probably entail the antigen to be one component of a multiantigenic vaccine.
authors.affiliation: Centre for Animal Biotechnology, University of Melbourne, Melbourne, Victoria, Australia. psutton@unimelb.edu.au
authors.forename: Philip
authors.initials: P
authors.lastname: Sutton
authors.forename: Christopher
authors.initials: C
authors.lastname: Doidge
authors.forename: Gideon
authors.initials: G
authors.lastname: Pinczower
authors.forename: John
authors.initials: J
authors.lastname: Wilson
authors.forename: Stacey
authors.initials: S
authors.lastname: Harbour
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Swierczak
authors.forename: Adrian
authors.initials: A
authors.lastname: Lee
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000276:immunology*; D002772:Cholera Toxin / Q000276:immunology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016481:Helicobacter Infections / Q000235:genetics* / Q000517:prevention & control* / Q000628:therapy; D016480:Helicobacter pylori / Q000254:growth & development / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013270:Stomach / Q000382:microbiology; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C095977:adhesin A, Helicobacter; D002772:Cholera Toxin