PDF(Pubmed)
Abstract：
Disseminated fungal infections account for ~1.5 million deaths per year worldwide, and mortality may increase further due to a rise in the number of immunocompromised individuals and drug-resistance fungal species. Since an approved antifungal vaccine is yet to be available, this study explored the immunogenicity and vaccine efficacy of a DNA polymerase mutant strain of Candida albicans. CNA25 is a pol32ΔΔ strain that exhibits growth defects and does not cause systemic candidiasis in mice. Immunized mice with live CNA25 were fully protected against C. albicans and C. parapsilosis but partially against C. tropicalis and C. glabrata infections. CNA25 induced steady expression of TLR2 and Dectin-1 receptors leading to a faster recognition and clearance by the immune system associated with the activation of protective immune responses mostly mediated by neutrophils, macrophages, NK cells, B cells, and CD4+ and CD8+ T cells. Molecular blockade of Dectin-1, IL-17, IFNγ, and TNFα abolished resistance to reinfection. Altogether, this study suggested that CNA25 collectively activates innate, adaptive, and trained immunity to be a promising live whole-cell vaccine against systemic candidiasis.
摘要：
播散性真菌感染占全球每年约150万例死亡。和死亡率可能进一步增加，由于免疫受损个体和耐药性真菌物种的数量增加。由于尚未获得批准的抗真菌疫苗，本研究探讨了白色念珠菌DNA聚合酶突变株的免疫原性和疫苗效力。CNA25是在小鼠中表现出生长缺陷并且不引起系统性念珠菌病的pol32ΔΔΔ菌株。用活的CNA25免疫的小鼠完全保护免受白色念珠菌和近扁平念珠菌感染,但部分保护免受热带念珠菌和光滑念珠菌感染。CNA25诱导TLR2和Dectin-1受体的稳定表达，导致免疫系统更快的识别和清除，这与主要由中性粒细胞介导的保护性免疫反应的激活有关。巨噬细胞，NK细胞,B细胞,和CD4+和CD8+T细胞。Dectin-1，IL-17，IFNγ的分子阻断，和TNFα消除了对再感染的抵抗力。总之,这项研究表明，CNA25集体激活先天，适应性，和训练的免疫力是一个有前途的活的全细胞疫苗对抗系统性念珠菌病。
