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Immunogenicity and efficacy of CNA25 as a potential whole-cell vaccine against systemic candidiasis.
EMBO Molecular Medicine ( IF 9.0 ) Pub Date : 2024-05-23 , DOI: 10.1038/s44321-024-00080-8
Satya Ranjan Sahu 1, 2 , Abinash Dutta 1 , Doureradjou Peroumal 1 , Premlata Kumari 1, 2 , Bhabasha Gyanadeep Utakalaja 1, 2 , Shraddheya Kumar Patel 1, 2 , Narottam Acharya 1
Affiliation  

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.

中文翻译:


CNA25 作为针对系统性念珠菌病的潜在全细胞疫苗的免疫原性和功效。



播散性真菌感染每年导致全世界约 150 万人死亡,并且由于免疫功能低下个体和耐药真菌种类数量的增加,死亡率可能进一步增加。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功效。 CNA25 是一种 pol32ΔΔ 菌株,表现出生长缺陷,并且不会引起小鼠全身性念珠菌病。用活 CNA25 免疫的小鼠可以完全抵抗白色念珠菌和近光滑念珠菌感染,但部分抵抗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,导致免疫系统更快地识别和清除,这与主要由中性粒细胞、巨噬细胞、NK 细胞、B 细胞以及 CD4+ 和 CD8+ T 细胞介导的保护性免疫反应的激活有关。 Dectin-1、IL-17、IFNγ和TNFα的分子阻断消除了对再感染的抵抗力。总而言之,这项研究表明,CNA25 共同激活先天性、适应性和经过训练的免疫力,成为一种有前景的针对系统性念珠菌病的全细胞活疫苗。
更新日期:2024-05-23
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