Abstract
Several pathogenic fungi, including Cryptococcus gattii, Histoplasma capsulatum, Coccidioides immitis, and Penicillium marneffei, cause serious infectious diseases in immunocompetent humans. However, currently, prophylactic and therapeutic vaccines are not clinically used. In particular, C. gattii is an emerging pathogen and thus far protective immunity against this pathogen has not been well characterized. Experimental vaccines such as component and attenuated live vaccines have been used as tools to study protective immunity against fungal infection. Recently, we developed a dendritic cell (DC)-based vaccine to study protective immunity against pulmonary infection by highly virulent C. gattii strain R265 that was clinically isolated from bronchial washings of infected patients during the Vancouver Island outbreak. In this approach, bone marrow-derived DCs (BMDCs) are pulsed with heat-killed C. gattii and then transferred into mice prior to intratracheal infection. This DC vaccine significantly increases interleukin 17A (IL-17A)-, interferon gamma (IFN-γ)-, and tumor necrosis factor alpha (TNF-α)-producing T cells in the lungs and spleen and ameliorates the pathology, fungal burden, and mortality following C. gattii infection. This approach may result in the development of a new means of controlling lethal fungal infections. In this chapter, we describe the procedures of DC vaccine preparation and murine pulmonary infection model for analysis of immune response against C. gattii.
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Acknowledgements
This chapter described work supported by Health Science Research Grants for Research on Emerging and Re-emerging Infectious Diseases (H25-Shinkou-Shitei-001, H25-Shinkou-Shitei-002, H25-Shinkou-Wakate-005, H25-Shinkou-Ippan-006, and H26-Shinkoujitsuyouka-Ippan-010) from the Ministry of Health, Labor and Welfare of Japan, by the Research program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and development, AMED, by KAKENHI (15K21644) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by a grant from the NOVARTIS Foundation (Japan) for the Promotion of Science.
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Ueno, K., Urai, M., Ohkouchi, K., Miyazaki, Y., Kinjo, Y. (2016). Dendritic Cell-Based Vaccine Against Fungal Infection. In: Thomas, S. (eds) Vaccine Design. Methods in Molecular Biology, vol 1403. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3387-7_30
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DOI: https://doi.org/10.1007/978-1-4939-3387-7_30
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