Immunogenicity and efficacy of CNA25 as a potential whole-cell vaccine against systemic candidiasis.

Autor:	Sahu SR; Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India.; Regional Center for Biotechnology, Faridabad, Haryana, 751021, India., Dutta A; Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India., Peroumal D; Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India., Kumari P; Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India.; Regional Center for Biotechnology, Faridabad, Haryana, 751021, India., Utakalaja BG; Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India.; Regional Center for Biotechnology, Faridabad, Haryana, 751021, India., Patel SK; Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India.; Regional Center for Biotechnology, Faridabad, Haryana, 751021, India., Acharya N; Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India. narottam_acharya@ils.res.in.
Jazyk:	angličtina
Zdroj:	EMBO molecular medicine [EMBO Mol Med] 2024 Jun; Vol. 16 (6), pp. 1254-1283. Date of Electronic Publication: 2024 May 23.
DOI:	10.1038/s44321-024-00080-8
Abstrakt:	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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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