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CANDIDA ADHERENCE MYCOLOGY RESEARCH UNIT

念珠菌粘附真菌学研究单位

基本信息

批准号：
6631877
负责人：
John E Edwards
金额：
$ 93.99万
依托单位：
LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1995
资助国家：
美国
起止时间：
1995-01-01 至 2005-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6631877
关键词：
Candida albicans candidiasis cell adhesion fungal vaccines

项目摘要

This proposal for a Mycology Research Unit (MRU) is focused on a comprehensive effort to identify and evaluate the ability the ability of candidate antigens to produce protective immunity against hematogenously disseminated candidiasis. The driving forces behind this effort are the high frequency of candidal infections, the attractiveness of a future DNA vaccine strategy, and the need for treatment approaches that will minimize the development of antifungal resistance. Project 1 builds on the discovery during the current grant period that antibody response to certain epitopes of the phosphomannan complex of C. albicans enhances resistance to experimental disseminated candidiasis. Approaches for the proposed period include: i) use of stabilized liposomal constructs to improve the liposomal vaccine formulations, ii) production of protein conjugates of the critical mannan epitopes, and iii) construction of a DNA vaccine based on peptide mimotopes of the "protective" mannan epitopes. Project 2 is based on the central hypothesis that the ASL (agglutinin mimotopes of the "protective" mannan epitopes. Project 2 is based on the central hypothesis that the ASL (agglutinin like sequence) gene family of Candida contains genes that encode dominant adhesions of Candida for a variety of host constituents. Gene products of the ALS gene family will be evaluated as potential vaccine targets for both active and passive immunization. The active immunization will be accomplished using DNA vaccine approaches and may be used in combination with phosphomannan antigens identified in project 1 to optimize an immune response. Project 3 will utilize the ability of affinity-purify large amounts of anti-mannan antibodies from human plasma to directly test the biological activities of these antibodies and the contribution to protection of the fine epitope specificity of human anti-mannan antibody. Project 4 utilizes highly innovative molecular biology strategies to identify yet undiscovered cell surface proteins that may be attractive vaccine targets. Genes that are expressed during infection will be identified by screening of random fusion genes. Comparison of functional sequences to the C. albicans genomic sequence will permit identification of likely secreted, cell wall, and transmembrane proteins, available for interaction with antibody. These gene products can then be used either alone or in combination with other target immunogens to develop effective vaccines. This technology lends itself well to the incorporation of multiple candidate immunogens into DNA vaccines.

该真菌学研究单位（MRU）的建议集中在一个全面的努力，以确定和评估候选抗原的能力，以产生对血源性传播的念珠菌病的保护性免疫的能力。这一努力背后的驱动力是念珠菌感染的高频率，未来DNA疫苗策略的吸引力，以及对治疗方法的需求，将最大限度地减少抗真菌药物耐药性的发展。项目1建立在当前资助期间的发现基础上，即抗体对C.白念珠菌增强对实验性播散性念珠菌病的抵抗力。在建议的时间段内的方法包括：i）使用稳定的脂质体构建体来改进脂质体疫苗制剂，ii）生产关键甘露聚糖表位的蛋白质缀合物，以及iii）基于“保护性”甘露聚糖表位的肽模拟表位构建DNA疫苗。项目2是基于中心假设，即ASL（凝集素模拟表位的“保护性”甘露聚糖表位。项目2基于中心假设，即念珠菌ASL（凝集素样序列）基因家族包含编码念珠菌对多种宿主成分的显性粘附的基因。ALS基因家族的基因产物将作为主动和被动免疫的潜在疫苗靶标进行评估。主动免疫将使用DNA疫苗方法完成，并可与项目1中鉴定的磷甘露聚糖抗原组合使用，以优化免疫应答。项目3将利用从人血浆中亲和纯化大量抗甘露聚糖抗体的能力，直接检测这些抗体的生物学活性以及对人抗甘露聚糖抗体的精细表位特异性保护的贡献。项目4利用高度创新的分子生物学策略来鉴定尚未发现的可能是有吸引力的疫苗靶点的细胞表面蛋白。通过筛选随机融合基因来鉴定感染期间表达的基因。与C.白色念珠菌基因组序列将允许鉴定可用于与抗体相互作用的可能分泌的、细胞壁和跨膜蛋白。然后，这些基因产物可以单独使用或与其他靶免疫原组合使用，以开发有效的疫苗。这种技术很适合于将多种候选免疫原掺入DNA疫苗中。

项目成果

期刊论文数量（39）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Human recombinant antimannan immunoglobulin G1 antibody confers resistance to hematogenously disseminated candidiasis in mice.

人重组抗甘露聚糖免疫球蛋白 G1 抗体赋予小鼠对血源性念珠菌病的抵抗力。

DOI：
10.1128/iai.74.1.362-369.2006
发表时间：
2006
期刊：
Infection and immunity
影响因子：
3.1
作者：
Zhang,MasonX;Bohlman,MCharlotte;Itatani,Carol;Burton,DennisR;Parren,PaulWHI;StJeor,StephenC;Kozel,ThomasR
通讯作者：
Kozel,ThomasR

Mannan-specific immunoglobulin G antibodies in normal human serum mediate classical pathway initiation of C3 binding to Candida albicans.

正常人血清中的甘露聚糖特异性免疫球蛋白 G 抗体介导 C3 与白色念珠菌结合的经典途径启动。