Stanford University, Stanford, CA, USA.
Department of Medicine, Santa Clara Valley Medical Center, San Jose, CA, USA.
J Med Microbiol. 2011 Oct;60(Pt 10):1423-1432. doi: 10.1099/jmm.0.033290-0. Epub 2011 Aug 8.
The mortality of clinical Aspergillus infections necessitates consideration of the utility of a vaccine. We have found that Saccharomyces species can act as a protective vaccine against a lethal systemic Aspergillus infection, and describe experiments optimizing a subcutaneous regimen with killed yeast. Three injections of 2.5 mg given a week apart, 2 weeks prior to challenge, consistently, significantly, provided survival protection and reduction of infection in organs in survivors. The protection was independent of the strain of Saccharomyces, and possibly even the species, and could be demonstrated in several inbred (including C'-deficient) and outbred mouse strains. The protective moiety(ies) appeared to reside in the cell wall and was resistant to 100 °C, but not to protease or formalin. Alum potentiated the protection. The protection was comparable or superior to that of several Aspergillus-specific preparations described in the literature. Other studies have indicated that heat-killed Saccharomyces can protect against infection with at least three other fungal genera, raising the possibility of development of a panfungal vaccine, and such a vehicle has been studied in clinical trials, without dose-limiting toxicity.
临床曲霉菌感染的死亡率需要考虑疫苗的效用。我们发现酿酒酵母可以作为一种预防致命系统性曲霉菌感染的保护性疫苗,并描述了优化用灭活酵母进行皮下方案的实验。在挑战前 2 周,每周间隔给予 2.5mg 的 3 次注射,可始终显著提供生存保护,并减少幸存者器官中的感染。这种保护与酿酒酵母的菌株无关,甚至可能与物种无关,并且可以在几种近交(包括 C'缺陷)和远交小鼠品系中证明。保护部分似乎存在于细胞壁中,并且对 100°C 具有抗性,但对蛋白酶或福尔马林没有抗性。明矾增强了保护作用。这种保护与文献中描述的几种针对曲霉菌的制剂相当或更好。其他研究表明,热灭活的酿酒酵母可以预防至少三种其他真菌属的感染,这增加了开发泛真菌疫苗的可能性,并且已经在临床试验中研究了这种载体,没有剂量限制毒性。