Vilanova Manuel, Teixeira Luzia, Caramalho Iris, Torrado Egídio, Marques Andreia, Madureira Pedro, Ribeiro Adília, Ferreira Paula, Gama Miguel, Demengeot Jocelyne
Laboratório de Imunologia Mário Arala Chaves, Instituto de Ciências Biomédicas de Abel Salazar, Largo do Prof. Abel Salazar 2, 4099-003 Porto, Portugal.
Immunology. 2004 Mar;111(3):334-42. doi: 10.1111/j.1365-2567.2004.01819.x.
Secreted aspartic proteinases (Sap) have been described as virulence factors implicated in the mechanisms of host colonization by the yeast Candida albicans in different types of candidiasis. Intraperitoneal inoculation of C. albicans into BALB/c mice rapidly leads to systemic candidiasis, with significant colonization of the kidneys measurable in the following week. In this study we assessed the potential of vaccination with C. albicans secreted aspartic proteinase 2 (Sap2) in preventing systemic candidiasis in BALB/c mice. Intradermal injection of highly purified native Sap2 protein incorporated in alum adjuvant provided efficient immune protection, as indicated by a 20-fold decrease in the colonization of kidneys. The protective effect of Sap2 immunization with alum adjuvant was also observed in mice infected with a lethal inoculum of C. albicans. Immunization with the native Sap2 alone, as well as with a denatured recombinant form of the protein, also conferred protection, albeit to a lesser level. In all cases, protection correlated with an increase in serum antibodies to Sap2. Moreover, passive transfer of anti-Sap2 immunoglobulin G (IgG) significantly decreased the yeast burden in kidneys of C. albicans-infected mice. This result shows that immune protection against systemic candidiasis in mice immunized with Sap2 is antibody-mediated. Taken together, these analyses demonstrate that Sap2 can be successfully used as a vaccination target in systemic candidiasis and reveals the potential immunomodulatory role of Sap2 on C. albicans infection.
分泌型天冬氨酸蛋白酶(Sap)被认为是白色念珠菌在不同类型念珠菌病中参与宿主定植机制的毒力因子。将白色念珠菌腹腔接种到BALB/c小鼠体内会迅速导致系统性念珠菌病,在接下来的一周内可检测到肾脏有明显的定植。在本研究中,我们评估了用白色念珠菌分泌型天冬氨酸蛋白酶2(Sap2)进行疫苗接种预防BALB/c小鼠系统性念珠菌病的潜力。皮内注射掺入明矾佐剂的高度纯化天然Sap2蛋白可提供有效的免疫保护,肾脏定植减少20倍表明了这一点。在感染致死剂量白色念珠菌的小鼠中也观察到了明矾佐剂Sap2免疫的保护作用。单独用天然Sap2以及该蛋白的变性重组形式进行免疫也能提供保护,尽管程度较低。在所有情况下,保护作用都与抗Sap2血清抗体的增加相关。此外,抗Sap2免疫球蛋白G(IgG)的被动转移显著降低了白色念珠菌感染小鼠肾脏中的酵母负荷。这一结果表明,用Sap2免疫的小鼠对系统性念珠菌病的免疫保护是由抗体介导的。综上所述,这些分析表明Sap2可成功用作系统性念珠菌病的疫苗接种靶点,并揭示了Sap2对白色念珠菌感染的潜在免疫调节作用。