Design of a mimotope-peptide based double epitope vaccine against candidiasis

描述（由申请人提供）：播散性念珠菌病是一种危及生命的疾病，在美国和许多欧洲国家住院患者中仍然是第三大最常见的血液感染。我们的疾病管理战略是通过免疫或预先形成的抗体进行预防，而不是治疗。我们的实验室已经成功地使用了一种新的全合成的针对白色念珠菌细胞表面表位的肽和糖肽疫苗来对抗小鼠播散性念珠菌病。强有力的证据表明，针对肽Fba（源自白色念珠菌细胞表面蛋白果糖二磷酸醛缩酶）和白色念珠菌细胞表面ß- 1,2 -甘露糖[ß-(Man)3])的特异性抗体有助于保护。因此，这种糖肽疫苗[ß-(Man)3-Fba]能够提供双重免疫识别，以帮助确保对白色念珠菌的保护性免疫。我们还证明了在合成的糖肽偶联物中加入破伤风类毒素

DESCRIPTION (provided by applicant): Disseminated candidiasis is a life-threatening disease and remains the third most common bloodstream infection in hospitalized patients both in the United States and many European countries. Our strategy for disease management is prevention, rather than treatment, through immunization or administration of preformed antibodies. Our lab has successfully used novel fully synthetic peptide and glycopeptide vaccines against Candida albicans cell surface epitopes combat disseminated candidiasis in mice. Strong evidences show that antibodies specific for the peptide Fba (derived from C. albicans cell surface protein fructose bisphosphate aldolase) and C. albicans cell surface ß-1, 2-mannotriose [ß-(Man)3]) contribute to the protection. Therefore, this glycopeptide vaccine [ß-(Man)3-Fba] is able to provide dual immune recognition to help ensure protective immunity against C. albicans. We also demonstrated that addition of tetanus toxoid to the synthetic glycopeptide conjugate vaccine ß-(Man)3-Fba-TT) induced antibody-dependent protective immunity without the need for adjuvant, which are a major step forward in a vaccine for human use. Most recently, we have identified a panel of novel peptide mimotopes, which structurally mimics protective epitope ß-(Man)3, as surrogate immunogens that substitute glycan part of glycopeptide vaccine. The overall goal of this research is to design and test a new mimotope-peptide based double epitope vaccine feasible for human use. Furthermore, we will test the efficacy of glycopeptide conjugate vaccine, as well as the new mimotope-peptide based vaccine(s), in a new mouse model that closely simulates humans by having protracted GI tract colonization with C. albicans. In Aim 1, we will modify the glycopeptide conjugate ß-(Man)3-Fba by taking place of glycan part with newly identified peptide-mimotope. In Aim 2, mice will be modified to have protracted GI tract colonization with C. albicans, and vaccine efficacy will be tested under host conditions that more closely simulate those of humans.