Whole glucan particles as a vaccine against systemic coccidioidomycosis Free

Abstract

We reported previously that yeast-derived whole glucan particles (WGPs), with or without conjugation to BSA, used as a vaccine protected against systemic aspergillosis in mice. Here, we examined their utility as a potential vaccine against coccidioidomycosis. WGPs were prepared from ; conjugation with BSA (WGP–BSA) was done using 1-cyano-4-dimethylaminopyridinium tetrafluoroborate-mediated conjugation. Heat-killed (HKY) was used as a positive-control vaccine. CD-1 mice were vaccinated with WGPs or WGP–BSA, HKY or PBS once weekly, beginning 21 days prior to infection. Mice were infected intravenously with arthroconidia of . In the low-mortality study, 50 % of PBS-treated controls died. Only WGP–BSA at 0.6 mg per dose induced significant protection compared with PBS treatment. All surviving mice were infected in all three organs examined. Those given WGP–BSA at 0.6 mg per dose had fewer c.f.u. in liver and lungs ( = 0.04), and those given WGPs at 6 mg per dose had fewer in lungs ( < 0.02), compared with PBS. In the high-mortality study, 90 % of PBS mice died. Vaccination with HKY, and WGPs or WGP–BSA at 6 or 12 mg per dose significantly prolonged survival ( ≤ 0.05). No surviving mice were free of infection. HKY and WGP–BSA at 12 mg per dose reduced c.f.u. in the liver and lungs ( < 0.05) and WGP–BSA at 6 mg per dose reduced c.f.u. in the lungs ( < 0.05); unconjugated WGPs did not reduce infection. WGPs or WGP–BSA acted as a vaccine that protected against mortality caused by coccidioidomycosis. Thus, WGP protection against coccidioidomycosis and aspergillosis provides the basis for development of a pan-fungal vaccine.

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2015-10-01
2024-03-29
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References

  1. Capilla J., Clemons K. V., Liu M., Levine H. B., Stevens D. A. 2009; Saccharomyces cerevisiae as a vaccine against coccidioidomycosis. Vaccine 27:3662–3668 [View Article][PubMed]
    [Google Scholar]
  2. Chosewood L. C., Wilson D. E. 2009 Biosafety in Microbiological and Biomedical Laboratories Washington, DC: U.S. Department of Health and Human Services;
    [Google Scholar]
  3. Clemons K. V., Stevens D. A. 1992; Efficacies of amphotericin B lipid complex (ABLC) and conventional amphotericin B against murine coccidioidomycosis. J Antimicrob Chemother 30:353–363 [View Article][PubMed]
    [Google Scholar]
  4. Clemons K. V., Stevens D. A. 1994; Utility of the triazole D0870 in the treatment of experimental systemic coccidioidomycosis. J Med Vet Mycol 32:323–326 [View Article][PubMed]
    [Google Scholar]
  5. Clemons K. V., Stevens D. A. 2011; Vaccines against coccidioidomycosis: past and current developments. J Invasive Fungal Infect 5:99–109
    [Google Scholar]
  6. Clemons K. V., Leathers C. R., Lee K. W. 1983 Protection of mice against experimental coccidioidomycosis induced by ribosome-rich extracts. American Society for Microbiology, New Orleans: F78, p. 395
  7. Clemons K. V., Leathers C. R., Lee K. W. 1985a; Role of activated macrophages in resistance to experimental Coccidioides immitis infections. In Coccidioidomycosis: Proceedings of the Fourth International Conference pp. 149–159 Edited by Einstein H. E., Catanzaro A. Washington, DC: The National Foundation for Infectious Diseases;
    [Google Scholar]
  8. Clemons K. V., Leathers C. R., Lee K. W. 1985b; Systemic Coccidioides immitis infection in nude and beige mice. Infect Immun 47:814–821[PubMed]
    [Google Scholar]
  9. Clemons K. V., Hanson L. H., Perlman A. M., Stevens D. A. 1990; Efficacy of SCH39304 and fluconazole in a murine model of disseminated coccidioidomycosis. Antimicrob Agents Chemother 34:928–930 [View Article][PubMed]
    [Google Scholar]
  10. Clemons K. V., Homola M. E., Stevens D. A. 1995; Activities of the triazole SCH 51048 against Coccidioides immitis in vitro and in vivo. Antimicrob Agents Chemother 39:1169–1172 [View Article][PubMed]
    [Google Scholar]
  11. Clemons K. V., Grunig G., Sobel R. A., Mirels L. F., Rennick D. M., Stevens D. A. 2000; Role of IL-10 in invasive aspergillosis: increased resistance of IL-10 gene knockout mice to lethal systemic aspergillosis. Clin Exp Immunol 122:186–191 [View Article][PubMed]
    [Google Scholar]
  12. Clemons K. V., Danielson M. E., Michel K. S., Liu M., Ottoson N. C., Leonardo S. M., Martinez M., Chen V., Antonysamy M. A., Stevens D. A. 2014a; Whole glucan particles as a vaccine against murine aspergillosis. J Med Microbiol 63:1750–1759 [View Article][PubMed]
    [Google Scholar]
  13. Clemons K. V., Antonysamy M. A., Danielson M. E., Michel K. S., Martinez M., Chen V., Stevens D. A. 2014b; Whole glucan particles (WGP) as a vaccine against systemic coccidioidomycosis. In 54th Interscience Conference on Antimicrobial Agents and Chemotherapy abstract G-1894 Washington, DC: American Society for Microbiology;
    [Google Scholar]
  14. Cole G. T., Xue J. M., Okeke C. N., Tarcha E. J., Basrur V., Schaller R. A., Herr R. A., Yu J. J., Hung C. Y. 2004; A vaccine against coccidioidomycosis is justified and attainable. Med Mycol 42:189–216 [View Article][PubMed]
    [Google Scholar]
  15. Cole G. T., Hung C. Y., Sanderson S. D., Hurtgen B. J., Wüthrich M., Klein B. S., Deepe G. S., Ostroff G. R., Levitz S. M. 2013; Novel strategies to enhance vaccine immunity against coccidioidomycosis. PLoS Pathog 9:e1003768 [View Article][PubMed]
    [Google Scholar]
  16. Deresinski S. C., Stevens D. A. 1975; Coccidioidomycosis in compromised hosts. Experience at Stanford University Hospital. Medicine (Baltimore) 54:377–395 [View Article][PubMed]
    [Google Scholar]
  17. Dewsnup D. H., Galgiani J. N., Graybill J. R., Diaz M., Rendon A., Cloud G. A., Stevens D. A. 1996; Is it ever safe to stop azole therapy for Coccidioides immitis meningitis?. Ann Intern Med 124:305–310 [View Article][PubMed]
    [Google Scholar]
  18. Galgiani J. N., Ampel N. M., Blair J. E., Catanzaro A., Johnson R. H., Stevens D. A., Williams P. L. 2005; Infectious Diseases Society of America Coccidioidomycosis. Clin Infect Dis 41:1217–1223 [View Article][PubMed]
    [Google Scholar]
  19. Hurtgen B. J., Hung C. Y., Ostroff G. R., Levitz S. M., Cole G. T. 2012; Construction and evaluation of a novel recombinant T cell epitope-based vaccine against coccidioidomycosis. Infect Immun 80:3960–3974 [View Article][PubMed]
    [Google Scholar]
  20. Lachin J. M. 1999; Worst-rank score analysis with informatively missing observations in clinical trials. Control Clin Trials 20:408–422 [View Article][PubMed]
    [Google Scholar]
  21. Li K., Yu J. J., Hung C. Y., Lehmann P. F., Cole G. T. 2001; Recombinant urease and urease DNA of Coccidioides immitis elicit an immunoprotective response against coccidioidomycosis in mice. Infect Immun 69:2878–2887 [View Article][PubMed]
    [Google Scholar]
  22. Liu M., Clemons K., Bystricky S., Stevens D. 2010; Glycans and conjugates as vaccines against coccidioidomycosis. In 50th Interscience Conference on Antimicrobial Agents and Chemotherapy abstract G1–G1657 Boston, MA:
    [Google Scholar]
  23. Liu M., Capilla J., Johansen M. E., Alvarado D., Martinez M., Chen V., Clemons K. V., Stevens D. A. 2011a; Saccharomyces as a vaccine against systemic aspergillosis: ‘the friend of man’ a friend again?. J Med Microbiol 60:1423–1432 [View Article][PubMed]
    [Google Scholar]
  24. Liu M., Clemons K. V., Bigos M., Medovarska I., Brummer E., Stevens D. A. 2011b; Immune responses induced by heat killed Saccharomyces cerevisiae: a vaccine against fungal infection. Vaccine 29:1745–1753 [View Article][PubMed]
    [Google Scholar]
  25. Liu M., Clemons K. V., Johansen M. E., Martinez M., Chen V., Stevens D. A. 2012a; Saccharomyces as a vaccine against systemic candidiasis. Immunol Invest 41:847–855 [View Article][PubMed]
    [Google Scholar]
  26. Liu M., Machová E., Neščáková Z., Medovarská I., Clemons K. V., Martinez M., Chen V., Bystrický S., Stevens D. A. 2012b; Vaccination with mannan protects mice against systemic aspergillosis. Med Mycol 50:818–828 [View Article][PubMed]
    [Google Scholar]
  27. Luo G., Gebremariam T., Clemons K. V., Stevens D. A., Ibrahim A. S. 2014; Heat-killed yeast protects diabetic ketoacidotic-steroid treated mice from pulmonary mucormycosis. Vaccine 32:3573–3576 [View Article][PubMed]
    [Google Scholar]
  28. Majumder T., Liu M., Chen V., Martinez M., Alvarado D., Clemons K. V., Stevens D. A. 2014; Killed Saccharomyces cerevisiae protects against lethal challenge of Cryptococcus grubii. Mycopathologia 178:189–195 [View Article][PubMed]
    [Google Scholar]
  29. National Research Council 2011 Guide for the Care and Use of Laboratory Animals, 8th edn. Washington, DC: The National Academies Press;
    [Google Scholar]
  30. Pappagianis D. 2001; Seeking a vaccine against Coccidioides immitis and serologic studies: expectations and realities. Fungal Genet Biol 32:1–9 [View Article][PubMed]
    [Google Scholar]
  31. Pappagianis D. 1993; The Valley Fever Vaccine Study Group Evaluation of the protective efficacy of the killed Coccidioides immitis spherule vaccine in humans. Am Rev Respir Dis 148:656–660 [View Article][PubMed]
    [Google Scholar]
  32. Shih W. 2002; Problems in dealing with missing data and informative censoring in clinical trials. Curr Control Trials Cardiovasc Med 3:4 [View Article][PubMed]
    [Google Scholar]
  33. Stevens D. A., Clemons K. V., Liu M. 2011; Developing a vaccine against aspergillosis. Med Mycol 49 (Suppl 1)S170–S176 [View Article][PubMed]
    [Google Scholar]
  34. Torosantucci A., Bromuro C., Chiani P., De Bernardis F., Berti F., Galli C., Norelli F., Bellucci C., Polonelli L., other authors. 2005; A novel glyco-conjugate vaccine against fungal pathogens. J Exp Med 202:597–606 [View Article][PubMed]
    [Google Scholar]
  35. Torosantucci A., Chiani P., Bromuro C., De Bernardis F., Palma A. S., Liu Y., Mignogna G., Maras B., Colone M., other authors. 2009; Protection by anti-β-glucan antibodies is associated with restricted β-1,3 glucan binding specificity and inhibition of fungal growth and adherence. PLoS One 4:e5392 [View Article][PubMed]
    [Google Scholar]
  36. Whibley N., Gaffen S. L. 2014; Brothers in arms: Th17 and Treg responses in Candida albicans immunity. PLoS Pathog 10:e1004456 [View Article][PubMed]
    [Google Scholar]
  37. Zelante T., De Luca A., D'Angelo C., Moretti S., Romani L. 2009; IL-17/Th17 in anti-fungal immunity: what's new?. Eur J Immunol 39:645–648 [View Article][PubMed]
    [Google Scholar]
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