Immunogenicity and Protective Efficacy of the WI-1 Adhesin of Blastomyces dermatitidis
AUTOR(ES)
Wüthrich, Marcel
FONTE
American Society for Microbiology
RESUMO
People infected with Blastomyces dermatitidis develop strong immunity to the yeast surface adhesin WI-1, including antibody responses to the adhesive domain, a 25-amino-acid repeat, and cellular responses to the N terminus. We studied the immunogenicity of WI-1 and the ability of anti-WI-1 immune responses to protect against lethal pulmonary infection in mice. WI-1 immunization, given in Freund’s adjuvant subcutaneously in two doses 2 weeks apart, evoked delayed hypersensitivity responses in a concentration-dependent manner. Immunized mice also had anti-WI-1 antibody responses, with titers reaching an endpoint dilution of approximately 1:800,000. Anti-WI-1 immunoglobulin G (IgG) antibody subclasses were IgG1 > IgG2b > IgG2a > IgG3, indicating a mixed T helper 1 and T helper 2 immune response. In protection experiments, WI-1 immunization significantly prolonged the survival of C57BL/6 and BALB/c mice compared to controls following intranasal administration of a lethal dose of B. dermatitidis yeasts (Kaplan-Meier survival curve P values of 0.027 to 0.0002) and also protected a proportion of the animals from death due to progressive pulmonary blastomycosis. Taken together, our results suggest that administration of WI-1 raises antibody and cell-mediated immune responses, which enhance resistance against pulmonary infection with B. dermatitidis. Mechanisms of vaccine-induced resistance require further investigation.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=108681Documentos Relacionados
- Interleukin 12 as an Adjuvant to WI-1 Adhesin Immunization Augments Delayed-Type Hypersensitivity, Shifts the Subclass Distribution of Immunoglobulin G Antibodies, and Enhances Protective Immunity to Blastomyces dermatitidis Infection
- Mutation of the WI-1 gene yields an attenuated Blastomyces dermatitidis strain that induces host resistance
- Purification and characterization of the major antigen WI-1 from Blastomyces dermatitidis yeasts and immunological comparison with A antigen.
- African strains of Blastomyces dermatitidis that do not express surface adhesin WI-1.
- Altered expression of surface protein WI-1 in genetically related strains of Blastomyces dermatitidis that differ in virulence regulates recognition of yeasts by human macrophages.
