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Vaccine development has been hampered though, by lack of knowledge as to which antigens are immunoprotective and the need for an effective vaccine delivery system. We made alkaline extracts from mutant cryptococcal strains that lacked capsule or chitosan. The extracts were then packaged into glucan particles (GPs), which are purified<jats:named-content content-type=\"genus-species\">Saccharomyces cerevisiae<\/jats:named-content>cell walls composed primarily of \u03b2-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>and<jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>. The alkaline extract derived from the acapsular strain was analyzed by liquid chromatography tandem mass spectrometry (LC-MS\/MS), and the most abundant proteins were identified. Separation of the alkaline extract by size exclusion chromatography revealed fractions that conferred protection when loaded in GP-based vaccines. Robust Th1- and Th17-biased CD4<jats:sup>+<\/jats:sup>T cell recall responses were observed in the lungs of vaccinated and infected mice. Thus, our preclinical studies have indicated promising cryptococcal vaccine candidates in alkaline extracts delivered in GPs. Ongoing studies are directed at identifying the individual components of the extracts that confer protection and thus would be promising candidates for a human vaccine.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>The encapsulated yeast<jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>and its closely related sister species,<jats:named-content content-type=\"genus-species\">Cryptococcus gattii<\/jats:named-content>, are major causes of morbidity and mortality, particularly in immunocompromised persons. This study reports on the preclinical development of vaccines to protect at-risk populations from cryptococcosis. Antigens were extracted from<jats:italic>Cryptococcus<\/jats:italic>by treatment with an alkaline solution. The extracted antigens were then packaged into glucan particles, which are hollow yeast cell walls composed mainly of \u03b2-glucans. The glucan particle-based vaccines elicited robust T cell immune responses and protected mice from otherwise-lethal challenge with virulent strains of<jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>and<jats:named-content content-type=\"genus-species\">C. gattii<\/jats:named-content>. The technology used for antigen extraction and subsequent loading into the glucan particle delivery system is relatively simple and can be applied to vaccine development against other pathogens.<\/jats:p>","DOI":"10.1128\/mbio.01905-15","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T01:07:50Z","timestamp":1450832870000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":83,"title":["Protection against Experimental Cryptococcosis following Vaccination with Glucan Particles Containing<i>Cryptococcus<\/i>Alkaline Extracts"],"prefix":"10.1128","volume":"6","author":[{"given":"Charles A.","family":"Specht","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrono 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