Department of Medicine, Division of Infectious Diseases and Immunology; Program in Molecular Medicine; Department of Pathology
Bacterial Infections and Mycoses | Bioinformatics | Immunoprophylaxis and Therapy
Development of a vaccine to protect against cryptococcosis is a priority given the enormous global burden of disease in at-risk individuals. Using glucan particles (GPs) as a delivery system, we previously demonstrated that mice vaccinated with crude Cryptococcus-derived alkaline extracts were protected against lethal challenge with Cryptococcus neoformans and Cryptococcus gattii The goal of the present study was to identify protective protein antigens that could be used in a subunit vaccine. Using biased and unbiased approaches, six candidate antigens (Cda1, Cda2, Cda3, Fpd1, MP88, and Sod1) were selected, recombinantly expressed in Escherichia coli, purified, and loaded into GPs. Three mouse strains (C57BL/6, BALB/c, and DR4) were then vaccinated with the antigen-laden GPs, following which they received a pulmonary challenge with virulent C. neoformans and C. gattii strains. Four candidate vaccines (GP-Cda1, GP-Cda2, GP-Cda3, and GP-Sod1) afforded a significant survival advantage in at least one mouse model; some vaccine combinations provided added protection over that seen with either antigen alone. Vaccine-mediated protection against C. neoformans did not necessarily predict protection against C. gattii Vaccinated mice developed pulmonary inflammatory responses that effectively contained the infection; many surviving mice developed sterilizing immunity. Predicted T helper cell epitopes differed between mouse strains and in the degree to which they matched epitopes predicted in humans. Thus, we have discovered cryptococcal proteins that make promising candidate vaccine antigens. Protection varied depending on the mouse strain and cryptococcal species, suggesting that a successful human subunit vaccine will need to contain multiple antigens, including ones that are species specific.
Cryptococcus, bioinformatics, glucans, immunization, major histocompatibility complex
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Copyright © 2017 Specht et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
DOI of Published Version
MBio. 2017 Nov 28;8(6). pii: mBio.01872-17. doi: 10.1128/mBio.01872-17. Link to article on publisher's site
Specht CA, Lee CK, Huang H, Hester MM, Liu J, Luckie BA, Torres Santana MA, Mirza Z, Khoshkenar P, Abraham A, Shen ZT, Akalin A, Ostroff GR, Levitz SM. (2017). Vaccination with Recombinant Cryptococcus Proteins in Glucan Particles Protects Mice against Cryptococcosis in a Manner Dependent upon Mouse Strain and Cryptococcal Species. Open Access Articles. https://doi.org/10.1128/mBio.01872-17. Retrieved from https://escholarship.umassmed.edu/oapubs/3301
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This work is licensed under a Creative Commons Attribution 4.0 License.