ABSTRACT
An important obstacle to development of an effective vaccine against Helicobacter pylori is the lack of a suitable adjuvant. This study evaluated the effectiveness of ISCOMATRIX and ISCOM vaccines at inducing protective immunity against H. pylori in mice. Immunisation with ISCOMATRIX and ISCOM vaccines resulted in a reduction in H. pylori colonisation equivalent to that induced by the gold standard cholera toxin (CT) adjuvant. Protection was induced in two mouse backgrounds, using two different bacterial antigens and following vaccine delivery via either the intranasal or subcutaneous route. This supports the potential of ISCOMATRIX and ISCOM technologies in H. pylori vaccine development.
Subject(s)
Adjuvants, Immunologic/pharmacology , Bacterial Vaccines/immunology , Cholesterol/pharmacology , Helicobacter Infections/prevention & control , Helicobacter pylori/immunology , ISCOMs/pharmacology , Phospholipids/pharmacology , Saponins/pharmacology , Adjuvants, Immunologic/administration & dosage , Administration, Intranasal , Animals , Antibodies, Bacterial/blood , Cholera Toxin/administration & dosage , Cholera Toxin/pharmacology , Cholesterol/administration & dosage , Colony Count, Microbial , Drug Combinations , Female , ISCOMs/administration & dosage , Injections, Subcutaneous , Mice , Phospholipids/administration & dosage , Saponins/administration & dosage , Stomach/microbiologyABSTRACT
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.
