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Although this infection is potentially lethal, no prophylactic vaccine is yet commercially available, and the immune memory that enables prevention is still under investigation. These pathogens have a capsule layer for immune evasion and a sophisticated mechanism to advance the infection, and it is expected that these characteristics will make it difficult to develop prophylactic vaccines and to decipher the protective immunity. The current vaccine studies are focused on subunit, mRNA, DNA, and viral vector vaccines, with whole\u2010cell vaccines also proving successful against cryptococcal infections. Cryptococcal whole\u2010cell vaccines have been composed of highly immunostimulating strains with low\u2010pathogenicity that are modified by genetic recombination technology. Examples include the whole\u2010cell vaccines H99\u03b3, sgl1\u2206, fbp1\u2206, znf2<jats:sup>oe<\/jats:sup>, cda1\/2\/3\u2206, cap59\u2206, and cap60\u2206. Some of these whole\u2010cell vaccines were found to be highly effective in prolonging life and suppressing the fungal burden after an infection challenge in mice, and to be cross\u2010reactive to <jats:italic>C. neoformans<\/jats:italic>, <jats:italic>C. gattii<\/jats:italic>, and other fungal pathogens. Furthermore, for some vaccines, the protective effect can be retained even in an immunocompromised host depleted of CD4<jats:sup>+<\/jats:sup> T cells. These findings have provided new insights into protective immunity that should aid in vaccine development. In this review, we highlight the upsides and downsides of whole\u2010cell vaccines against cryptococcosis.<\/jats:p>","DOI":"10.1111\/1348-0421.13056","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T12:19:21Z","timestamp":1676377161000},"page":"211-223","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Promising whole\u2010cell vaccines against cryptococcosis"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0671-0049","authenticated-orcid":false,"given":"Keigo","family":"Ueno","sequence":"first","affiliation":[{"name":"Department of Fungal Infection National Institute of Infectious Diseases Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Tsuge","sequence":"additional","affiliation":[{"name":"Department of Fungal Infection National Institute of Infectious Diseases Tokyo 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