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dc.contributor.authorSpecht, Charles A.
dc.contributor.authorLee, Chrono K.
dc.contributor.authorHuang, Haibin
dc.contributor.authorTipper, Donald J.
dc.contributor.authorShen, Zu T.
dc.contributor.authorLodge, Jennifer K
dc.contributor.authorLeszyk, John D.
dc.contributor.authorOstroff, Gary R.
dc.contributor.authorLevitz, Stuart M.
dc.date2022-08-11T08:09:09.000
dc.date.accessioned2022-08-23T16:19:16Z
dc.date.available2022-08-23T16:19:16Z
dc.date.issued2015-12-22
dc.date.submitted2016-05-12
dc.identifier.citationMBio. 2015 Dec 22;6(6):e01905-15. doi: 10.1128/mBio.01905-15. <a href="http://dx.doi.org/10.1128/mBio.01905-15">Link to article on publisher's website</a>
dc.identifier.issn2150-7511
dc.identifier.doi10.1128/mBio.01905-15
dc.identifier.pmid26695631
dc.identifier.urihttp://hdl.handle.net/20.500.14038/35008
dc.description.abstractA vaccine capable of protecting at-risk persons against infections due to Cryptococcus neoformans and Cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. 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 Saccharomyces cerevisiae cell walls composed primarily of β-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of C. neoformans and C. gattii. 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(+) 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. IMPORTANCE: The encapsulated yeast Cryptococcus neoformans and its closely related sister species, Cryptococcus gattii, 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 Cryptococcus by treatment with an alkaline solution. The extracted antigens were then packaged into glucan particles, which are hollow yeast cell walls composed mainly of β-glucans. The glucan particle-based vaccines elicited robust T cell immune responses and protected mice from otherwise-lethal challenge with virulent strains of C. neoformans and C. gattii. 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=26695631&dopt=Abstract">Link to article in PubMed</a>
dc.rightsCopyright © 2015 Specht et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license</a>, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subjectBacterial Infections and Mycoses
dc.subjectImmunity
dc.subjectImmunology and Infectious Disease
dc.subjectImmunology of Infectious Disease
dc.subjectImmunoprophylaxis and Therapy
dc.subjectInfectious Disease
dc.subjectPathogenic Microbiology
dc.titleProtection against Experimental Cryptococcosis following Vaccination with Glucan Particles Containing Cryptococcus Alkaline Extracts
dc.typeJournal Article
dc.source.journaltitleMBio
dc.source.volume6
dc.source.issue6
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1225&amp;context=infdis_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/infdis_pp/226
dc.identifier.contextkey8594406
refterms.dateFOA2022-08-23T16:19:16Z
html.description.abstract<p>A vaccine capable of protecting at-risk persons against infections due to Cryptococcus neoformans and Cryptococcus gattii could reduce the substantial global burden of human cryptococcosis. 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 Saccharomyces cerevisiae cell walls composed primarily of β-1,3-glucans. Subcutaneous vaccination with the GP-based vaccines provided significant protection against subsequent pulmonary infection with highly virulent strains of C. neoformans and C. gattii. 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(+) 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.</p> <p>IMPORTANCE: The encapsulated yeast Cryptococcus neoformans and its closely related sister species, Cryptococcus gattii, 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 Cryptococcus by treatment with an alkaline solution. The extracted antigens were then packaged into glucan particles, which are hollow yeast cell walls composed mainly of β-glucans. The glucan particle-based vaccines elicited robust T cell immune responses and protected mice from otherwise-lethal challenge with virulent strains of C. neoformans and C. gattii. 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.</p>
dc.identifier.submissionpathinfdis_pp/226
dc.contributor.departmentDepartment of Biochemistry and Molecular Pharmacology
dc.contributor.departmentProgram in Molecular Medicine
dc.contributor.departmentDepartment of Microbiology and Physiological Systems
dc.contributor.departmentDepartment of Medicine, Division of Infectious Diseases and Immunology
dc.source.pagese01905-15


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Copyright © 2015 Specht et al.  This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license</a>, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright © 2015 Specht et al. This is an open-access article distributed under the terms of the <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license</a>, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.