The nontoxic CTA1-DD adjuvant enhances protective immunity against Helicobacter pylori infection following mucosal immunization.
Safe and efficacious adjuvants are much needed to facilitate the development of mucosal vaccines. Here, we have asked whether our nontoxic vaccine adjuvant, CTA1-DD, can enhance protective immunity against Helicobacter pylori infection. Intranasal immunizations with H. pylori lysate together with CTA1-DD-adjuvant induced significant protection in C57Bl/6 mice, almost as strong as similar immunizations using cholera toxin (CT)-adjuvant. Protection remained strong even at 8 weeks postchallenge and the bacterial colonization was reduced by 20-fold compared to lysate-immunized controls. Although CTA1-DD was designed to bind to B cells, microMT mice developed significant, but lower, level of protection following immunization. Intranasal immunizations with CT adjuvant in C57Bl/6 mice resulted in the development of severe postimmunization gastritis at 2 and 8 weeks postchallenge, whereas the degree of gastritis was substantially lower in the CTA1-DD-immunized mice. Protection induced by both CTA1-DD- and CT adjuvant was associated with a strong local infiltration of CD4(+) T cells in the gastric mucosa, and recall responses to specific Ag elicited substantial IFN-gamma production, indicating Th1-dominance. These findings clearly demonstrate that CTA1-DD adjuvant is a promising candidate to be further exploited in the development of a mucosal vaccine against H. pylori infection.
Department of Clinical Immunology, Göteborg University, Göteborg, Sweden.
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Akhiani
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Stensson
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Schön
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Lycke
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology / Q000494:pharmacology*; D002772:Cholera Toxin / Q000276:immunology / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology; D005260:Female; D005756:Gastritis / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology*; D007114:Immunization / Q000009:adverse effects / Q000379:methods; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology*; D013047:Specific Pathogen-Free Organisms; D018709:Statistics, Nonparametric; D018417:Th1 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; C440610:CTA1-DD protein, recombinant; D016207:Cytokines; D011993:Recombinant Fusion Proteins; D002772:Cholera Toxin