Nasal vaccination induces the ability to eliminate Candida colonization without influencing the pre-existing antigen-specific IgE Abs: a possibility for the control of Candida-related atopic dermatitis.
In some cases of atopic dermatitis (AD), a possible pathological contribution to disease development by Candida albicans (C. albicans) has been suggested. AD patients with severe symptoms showing positive capsulated hydrolic carrier polymer radioallergosorbent test (CAP-RAST) against C. albicans demonstrated significantly higher levels of serum IgE Abs than did AD patients with mild symptoms. Based on the clinical facts, we have postulated that elimination of C. albicans by mucosal vaccination may lead to the restoration of severe symptoms in AD patients. For this purpose, we have developed an allergic murine model. Mice which were systemically challenged with C. albicans-associated antigen, manganese superoxide dismutase (MnSOD) or secreted aspartic proteases 2 (SAP2), together with alum, exhibited hyper IgE Abs. Systemically primed mice were then immunized with MnSOD or SAP2 plus cholera toxin (CT) as mucosal adjuvant through the nasal route. Interestingly, nasally immunized mice showed increased levels of Candida Ag-specific IgA Ab in fecal and nasal washes as well as in saliva samples but unchanged levels in Ag-specific IgE responses. Consistent with the Ab levels, high numbers of Candida Ag-specific IgA Ab-forming cells were induced in mononuclear cells isolated from intestinal lamina propria, nasal passages and salivary glands of nasally vaccinated mice with Ag plus CT. Furthermore, nasal immunization using MnSOD or SAP2 together with CT resulted in the elimination of colonized C. albicans from the intestinal tract. These results also suggest a potential role of mucosal vaccination in the control of C. albicans in patients with allergic diseases, including AD, although more research is needed to establish this therapeutic approach for mucosal vaccination.
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Noriko
N
Suenobu
Mi-Na
MN
Kweon
Hiroshi
H
Kiyono
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000908:Antibodies, Fungal / Q000378:metabolism*; D000946:Antigens, Fungal; D016282:Aspartic Acid Endopeptidases / Q000276:immunology; D002176:Candida albicans / Q000201:enzymology / Q000254:growth & development / Q000276:immunology*; D002179:Candidiasis, Cutaneous / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D002772:Cholera Toxin / Q000008:administration & dosage; D003876:Dermatitis, Atopic / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D005260:Female; D005656:Fungal Proteins; D005657:Fungal Vaccines / Q000008:administration & dosage*; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000378:metabolism; D007073:Immunoglobulin E / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D013482:Superoxide Dismutase / Q000276:immunology
D000276:Adjuvants, Immunologic; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D005656:Fungal Proteins; D005657:Fungal Vaccines; D007070:Immunoglobulin A; D007073:Immunoglobulin E; D002772:Cholera Toxin; D013482:Superoxide Dismutase; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida