Feldmesser Marta
Division of Infectious Diseases, Department of Medicine, Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Med Mycol. 2005 Nov;43(7):571-87. doi: 10.1080/13693780500402138.
Invasive aspergillosis is a disease of immunocompromised hosts and the pathogenesis of this disorder is heavily dependent upon the defect within a given host. Consequently, vaccine development is limited by our understanding of effective host responses and by limitations in our knowledge of fungal molecules that elicit protective immunity. Nonetheless, the past few years have witnessed advances in our understanding both of the immune response to this organism and in the relationship between antigenicity and the ability to confer protection. Manipulations that promote the development of T(H)1-associated responses correlate with increased resistance to disease, at least partly because of consequent enhancement of innate cellular effector function. Two areas of investigation most actively being pursued include the search for adjuvants that will allow products of Aspergillus fumigatus to become effective vaccine candidates, regardless of the form of immunity they ordinarily induce, and the identification of the specific antigens that will most effectively elicit beneficial responses. Strategies using antigen-exposed dendritic cells as adjuvants appear to be particularly promising. Though we currently are far away from a candidate that is applicable for human trials, recent progress is encouraging.
侵袭性曲霉病是免疫功能低下宿主易患的疾病,该病症的发病机制在很大程度上取决于特定宿主的缺陷。因此,疫苗研发受到我们对有效宿主反应的理解以及对引发保护性免疫的真菌分子认识的限制。尽管如此,在过去几年中,我们对该生物体免疫反应以及抗原性与赋予保护能力之间关系的理解都取得了进展。促进T(H)1相关反应发展的操作与疾病抵抗力增强相关,至少部分原因是由此增强了先天性细胞效应功能。目前最积极开展的两个研究领域包括:寻找能使烟曲霉产物成为有效疫苗候选物的佐剂,而不论它们通常诱导何种免疫形式;以及鉴定最有效地引发有益反应的特定抗原。使用暴露抗原的树突状细胞作为佐剂的策略似乎特别有前景。虽然我们目前距离可用于人体试验的候选物还很遥远,但最近的进展令人鼓舞。