1932

Abstract

Invasive fungal infections are emerging diseases that kill over 1.5 million people per year worldwide. With the increase of immunocompromised populations, the incidence of invasive fungal infections is expected to continue to rise. Vaccines for viral and bacterial infectious diseases have had a transformative impact on human health worldwide. However, no fungal vaccines are currently in clinical use. Recently, interest in fungal vaccines has grown significantly. One vaccine has completed phase 2 clinical trials, and research on vaccines against coccidioidomycosis continues to advance. Additionally, multiple groups have discovered various mutant strains that promote protective responses to subsequent challenge in mouse models. There has also been progress in antibody-mediated fungal vaccines. In this review, we highlight recent fungal vaccine research progress, outline the wealth of data generated, and summarize current research for both fungal biology and immunology studies relevant to fungal vaccine development. We also review technological advancements in vaccine development and highlight the future prospects of a human vaccine against invasive fungal infections.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-micro-041020-111511
2022-09-08
2024-05-09
Loading full text...

Full text loading...

/deliver/fulltext/micro/76/1/annurev-micro-041020-111511.html?itemId=/content/journals/10.1146/annurev-micro-041020-111511&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Bar E, Whitney PG, Moor K, Reis e Sousa C, LeibundGut-Landmann S. 2014. IL-17 regulates systemic fungal immunity by controlling the functional competence of NK cells. Immunity 40:117–27
    [Google Scholar]
  2. 2.
    Bistoni F, Vecchiarelli A, Cenci E, Puccetti P, Marconi P, Cassone A. 1986. Evidence for macrophage-mediated protection against lethal Candida albicans infection. Infect. Immun. 51:668–74
    [Google Scholar]
  3. 3.
    Biswas PS. 2021. Vaccine-induced immunological memory in invasive fungal infections—a dream so close yet so far. Front. Immunol. 12:671068
    [Google Scholar]
  4. 4.
    Bongomin F, Gago S, Oladele RO, Denning DW. 2017. Global and multi-national prevalence of fungal diseases—estimate precision. J. Fungi 3:57
    [Google Scholar]
  5. 5.
    Bourgeois C, Kuchler K. 2012. Fungal pathogens—a sweet and sour treat for Toll-like receptors. Front. Cell Infect. Microbiol. 2:142
    [Google Scholar]
  6. 6.
    Buchanan KL, Doyle HA. 2000. Requirement for CD4+ T lymphocytes in host resistance against Cryptococcus neoformans in the central nervous system of immunized mice. Infect. Immun. 68:456–62
    [Google Scholar]
  7. 7.
    Caballero Van Dyke MC, Wormley FL Jr. 2018. A call to arms: quest for a cryptococcal vaccine. Trends Microbiol. 26:436–46
    [Google Scholar]
  8. 8.
    Caldera F, Mercer M, Samson SI, Pitt JM, Hayney MS. 2021. Influenza vaccination in immunocompromised populations: strategies to improve immunogenicity. Vaccine 39:Suppl. 1A15–23
    [Google Scholar]
  9. 9.
    Casadevall A, Cleare W, Feldmesser M, Glatman-Freedman A, Goldman DL et al. 1998. Characterization of a murine monoclonal antibody to Cryptococcus neoformans polysaccharide that is a candidate for human therapeutic studies. Antimicrob. Agents Chemother. 42:1437–46
    [Google Scholar]
  10. 10.
    Casadevall A, Pirofski L. 2005. Insights into mechanisms of antibody-mediated immunity from studies with Cryptococcus neoformans. Curr. Mol. Med. 5:421–33
    [Google Scholar]
  11. 11.
    Casadevall A, Pirofski LA. 2012. Immunoglobulins in defense, pathogenesis, and therapy of fungal diseases. Cell Host Microbe 11:447–56
    [Google Scholar]
  12. 12.
    Castro-Lopez N, Hung CY. 2017. Immune response to coccidioidomycosis and the development of a vaccine. Microorganisms 5:13
    [Google Scholar]
  13. 13.
    Cenci E, Mencacci A, Bacci A, Bistoni F, Kurup VP, Romani L. 2000. T cell vaccination in mice with invasive pulmonary aspergillosis. J. Immunol. 165:381–88
    [Google Scholar]
  14. 14.
    Chakraborty C, Sharma AR, Bhattacharya M, Lee SS. 2021. From COVID-19 to cancer mRNA vaccines: moving from bench to clinic in the vaccine landscape. Front. Immunol. 12:679344
    [Google Scholar]
  15. 15.
    Chauvin D, Hust M, Schutte M, Chesnay A, Parent C et al. 2019. Targeting Aspergillus fumigatus Crf transglycosylases with neutralizing antibody is relevant but not sufficient to erase fungal burden in a neutropenic rat model. Front. Microbiol. 10:600
    [Google Scholar]
  16. 16.
    Cheng G, Wozniak K, Wallig MA, Fidel PL Jr., Trupin SR, Hoyer LL 2005. Comparison between Candida albicans agglutinin-like sequence gene expression patterns in human clinical specimens and models of vaginal candidiasis. Infect. Immun. 73:1656–63
    [Google Scholar]
  17. 17.
    Cheng SC, Quintin J, Cramer RA, Shepardson KM, Saeed S et al. 2014. mTOR- and HIF-1α-mediated aerobic glycolysis as metabolic basis for trained immunity. Science 345:1250684
    [Google Scholar]
  18. 18.
    Chow SK, Casadevall A. 2011. Evaluation of Cryptococcus neoformans galactoxylomannan-protein conjugate as vaccine candidate against murine cryptococcosis. Vaccine 29:1891–98
    [Google Scholar]
  19. 19.
    Chuck SL, Sande MA. 1989. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N. Engl. J. Med. 321:794–99
    [Google Scholar]
  20. 20.
    Colombo AC, Rella A, Normile T, Joffe LS, Tavares PM et al. 2019. Cryptococcus neoformans glucuronoxylomannan and sterylglucoside are required for host protection in an animal vaccination model. mBio 10:e02909–18
    [Google Scholar]
  21. 21.
    Conti HR, Gaffen SL. 2015. IL-17-mediated immunity to the opportunistic fungal pathogen Candida albicans. J. Immunol. 195:780–88
    [Google Scholar]
  22. 22.
    Crum-Cianflone NF, Wallace MR 2014. Vaccination in HIV-infected adults. AIDS Patient Care STDs 28:397–410
    [Google Scholar]
  23. 23.
    Cutler JE, Deepe GS Jr., Klein BS. 2007. Advances in combating fungal diseases: vaccines on the threshold. Nat. Rev. Microbiol. 5:13–28
    [Google Scholar]
  24. 24.
    De Bernardis F, Amacker M, Arancia S, Sandini S, Gremion C et al. 2012. A virosomal vaccine against candidal vaginitis: immunogenicity, efficacy and safety profile in animal models. Vaccine 30:4490–98
    [Google Scholar]
  25. 25.
    de la Rua NM, Samuelson DR, Charles TP, Welsh DA, Shellito JE. 2016. CD4+ T-cell-independent secondary immune responses to Pneumocystis pneumonia. Front. Immunol. 7:178
    [Google Scholar]
  26. 26.
    Deatherage BL, Cookson BT. 2012. Membrane vesicle release in bacteria, eukaryotes, and archaea: a conserved yet underappreciated aspect of microbial life. Infect. Immun. 80:1948–57
    [Google Scholar]
  27. 27.
    Deepe GS Jr., Gibbons R. 2001. Protective efficacy of H antigen from Histoplasma capsulatum in a murine model of pulmonary histoplasmosis. Infect. Immun. 69:3128–34
    [Google Scholar]
  28. 28.
    Devi SJ. 1996. Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model. Vaccine 14:841–44
    [Google Scholar]
  29. 29.
    Diaz-Arevalo D, Ito JI, Kalkum M. 2012. Protective effector cells of the recombinant Asp f3 anti-aspergillosis vaccine. Front. Microbiol. 3:299
    [Google Scholar]
  30. 30.
    Divangahi M, Aaby P, Khader SA, Barreiro LB, Bekkering S et al. 2021. Trained immunity, tolerance, priming and differentiation: distinct immunological processes. Nat. Immunol. 22:2–6
    [Google Scholar]
  31. 31.
    Durkin M, Kohler S, Schnizlein-Bick C, LeMonte A, Connolly P et al. 2001. Chronic infection and reactivation in a pulmonary challenge model of histoplasmosis. J. Infect. Dis. 183:1822–24
    [Google Scholar]
  32. 32.
    Edwards JE Jr., Schwartz MM, Schmidt CS, Sobel JD, Nyirjesy P et al. 2018. A fungal immunotherapeutic vaccine (NDV-3A) for treatment of recurrent vulvovaginal candidiasis—a phase 2 randomized, double-blind, placebo-controlled trial. Clin. Infect. Dis. 66:1928–36
    [Google Scholar]
  33. 33.
    El Chaer F, El Sahly HM. 2019. Vaccination in the adult patient infected with HIV: a review of vaccine efficacy and immunogenicity. Am. J. Med. 132:437–46
    [Google Scholar]
  34. 34.
    Espinosa V, Rivera A. 2012. Cytokines and the regulation of fungus-specific CD4 T cell differentiation. Cytokine 58:100–6
    [Google Scholar]
  35. 35.
    Fernandez-Arenas E, Molero G, Nombela C, Diez-Orejas R, Gil C 2004. Low virulent strains of Candida albicans: unravelling the antigens for a future vaccine. Proteomics 4:3007–20
    [Google Scholar]
  36. 36.
    Fierer J, Waters C, Walls L. 2006. Both CD4+ and CD8+ T cells can mediate vaccine-induced protection against Coccidioides immitis infection in mice. J. Infect. Dis. 193:1323–31
    [Google Scholar]
  37. 37.
    Fleuridor R, Lees A, Pirofski L. 2001. A cryptococcal capsular polysaccharide mimotope prolongs the survival of mice with Cryptococcus neoformans infection. J. Immunol. 166:1087–96
    [Google Scholar]
  38. 38.
    Glesby MJ. 1998. Immunizations during HIV infection. Curr. Opin. Infect. Dis. 11:17–21
    [Google Scholar]
  39. 39.
    Gomez FJ, Allendoerfer R, Deepe GS Jr. 1995. Vaccination with recombinant heat shock protein 60 from Histoplasma capsulatum protects mice against pulmonary histoplasmosis. Infect. Immun. 63:2587–95
    [Google Scholar]
  40. 40.
    Hardison SE, Brown GD. 2012. C-type lectin receptors orchestrate antifungal immunity. Nat. Immunol. 13:817–22
    [Google Scholar]
  41. 41.
    Hatinguais R, Willment JA, Brown GD. 2020. PAMPs of the fungal cell wall and mammalian PRRs. Curr. Top. Microbiol. Immunol. 425:187–223
    [Google Scholar]
  42. 42.
    Hawksworth DL. 1991. The fungal dimension of biodiversity: magnitude, significance, and conservation. Mycol. Res. 95:641–55
    [Google Scholar]
  43. 43.
    Hernandez-Santos N, Huppler AR, Peterson AC, Khader SA, McKenna KC, Gaffen SL. 2013. Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections. Mucosal Immunol. 6:900–10
    [Google Scholar]
  44. 44.
    Hill JO, Harmsen AG. 1991. Intrapulmonary growth and dissemination of an avirulent strain of Cryptococcus neoformans in mice depleted of CD4+ or CD8+ T cells. J. Exp. Med. 173:755–58
    [Google Scholar]
  45. 45.
    Hole CR, Wager CML, Castro-Lopez N, Campuzano A, Cai H et al. 2019. Induction of memory-like dendritic cell responses in vivo. Nat. Commun. 10:2955
    [Google Scholar]
  46. 46.
    Hoyer LL, Cota E. 2016. Candida albicans agglutinin-like sequence (Als) family vignettes: a review of Als protein structure and function. Front. Microbiol. 7:280
    [Google Scholar]
  47. 47.
    Hoyer LL, Payne TL, Bell M, Myers AM, Scherer S. 1998. Candida albicans ALS3 and insights into the nature of the ALS gene family. Curr. Genet. 33:451–59
    [Google Scholar]
  48. 48.
    Huang C, Nong SH, Mansour MK, Specht CA, Levitz SM. 2002. Purification and characterization of a second immunoreactive mannoprotein from Cryptococcus neoformans that stimulates T-cell responses. Infect. Immun. 70:5485–93
    [Google Scholar]
  49. 49.
    Hube B, Sanglard D, Odds FC, Hess D, Monod M et al. 1997. Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence. Infect. Immun. 65:3529–38
    [Google Scholar]
  50. 50.
    Huffnagle GB, Lipscomb MF, Lovchik JA, Hoag KA, Street NE. 1994. The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection. J. Leukoc. Biol. 55:35–42
    [Google Scholar]
  51. 51.
    Huffnagle GB, Yates JL, Lipscomb MF. 1991. Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells. J. Exp. Med. 173:793–800
    [Google Scholar]
  52. 52.
    Hull CM, Heitman J. 2002. Genetics of Cryptococcus neoformans. Annu. Rev. Genet. 36:557–615
    [Google Scholar]
  53. 53.
    Huppler AR, Conti HR, Hernández-Santos N, Darville T, Biswas PS, Gaffen SL. 2014. Role of neutrophils in IL-17-dependent immunity to mucosal candidiasis. J. Immunol. 192:1745–52 Erratum 2015. J. Immunol. 194:1382
    [Google Scholar]
  54. 54.
    Ibrahim AS, Spellberg BJ, Avenissian V, Fu Y, Filler SG, Edwards JE Jr. 2005. Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity. Infect. Immun. 73:999–1005
    [Google Scholar]
  55. 55.
    Joffe LS, Nimrichter L, Rodrigues ML, Del Poeta M. 2016. Potential roles of fungal extracellular vesicles during infection. mSphere 1:e00099–16
    [Google Scholar]
  56. 56.
    Johannesson H, Vidal P, Guarro J, Herr RA, Cole GT, Taylor JW. 2004. Positive directional selection in the proline-rich antigen (PRA) gene among the human pathogenic fungi Coccidioides immitis, C. posadasii and their closest relatives. Mol. Biol. Evol. 21:1134–45
    [Google Scholar]
  57. 57.
    Kawakami K, Kohno S, Kadota J, Tohyama M, Teruya K et al. 1995. T cell-dependent activation of macrophages and enhancement of their phagocytic activity in the lungs of mice inoculated with heat-killed Cryptococcus neoformans: involvement of IFN-gamma and its protective effect against cryptococcal infection. Microbiol. Immunol. 39:135–43
    [Google Scholar]
  58. 58.
    Kelly MN, Zheng M, Ruan S, Kolls J, D'Souza A, Shellito JE 2013. Memory CD4+ T cells are required for optimal NK cell effector functions against the opportunistic fungal pathogen Pneumocystis murina. J. Immunol. 190:285–95
    [Google Scholar]
  59. 59.
    Kirkland TN. 2016. The quest for a vaccine against coccidioidomycosis: a neglected disease of the Americas. J. Fungi 2:34
    [Google Scholar]
  60. 60.
    Kischkel B, Rossi SA, Santos SR, Nosanchuk JD, Travassos LR, Taborda CP. 2020. Therapies and vaccines based on nanoparticles for the treatment of systemic fungal infections. Front. Cell. Infect. Microbiol. 10:463
    [Google Scholar]
  61. 61.
    Korting HC, Hube B, Oberbauer S, Januschke E, Hamm G et al. 2003. Reduced expression of the hyphal-independent Candida albicans proteinase genes SAP1 and SAP3 in the efg1 mutant is associated with attenuated virulence during infection of oral epithelium. J. Med. Microbiol. 52:623–32
    [Google Scholar]
  62. 62.
    Larsen RA, Pappas PG, Perfect J, Aberg JA, Casadevall A et al. 2005. Phase I evaluation of the safety and pharmacokinetics of murine-derived anticryptococcal antibody 18B7 in subjects with treated cryptococcal meningitis. Antimicrob. Agents Chemother. 49:952–58
    [Google Scholar]
  63. 63.
    Levitz SM, Nong S, Mansour MK, Huang C, Specht CA. 2001. Molecular characterization of a mannoprotein with homology to chitin deacetylases that stimulates T cell responses to Cryptococcus neoformans. PNAS 98:10422–27
    [Google Scholar]
  64. 64.
    Levitz SM, Specht CA. 2006. The molecular basis for the immunogenicity of Cryptococcus neoformans mannoproteins. FEMS Yeast Res. 6:513–24
    [Google Scholar]
  65. 65.
    Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K et al. 2006. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J. Exp. Med. 203:2271–79
    [Google Scholar]
  66. 66.
    Lin JS, Yang CW, Wang DW, Wu-Hsieh BA. 2005. Dendritic cells cross-present exogenous fungal antigens to stimulate a protective CD8 T cell response in infection by Histoplasma capsulatum. J. Immunol. 174:6282–91
    [Google Scholar]
  67. 67.
    Lindell DM, Moore TA, McDonald RA, Toews GB, Huffnagle GB. 2005. Generation of antifungal effector CD8+ T cells in the absence of CD4+ T cells during Cryptococcus neoformans infection. J. Immunol. 174:7920–28
    [Google Scholar]
  68. 68.
    Liu F, Fan X, Auclair S, Ferguson M, Sun J et al. 2016. Sequential dysfunction and progressive depletion of Candida albicans-specific CD4 T cell response in HIV-1 infection. PLOS Pathog. 12:e1005663
    [Google Scholar]
  69. 69.
    Liu TB, Xue C. 2014. Fbp1-mediated ubiquitin-proteasome pathway controls Cryptococcus neoformans virulence by regulating fungal intracellular growth in macrophages. Infect. Immun. 82:557–68
    [Google Scholar]
  70. 70.
    Liu Y, Filler SG. 2011. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot. Cell 10:168–73
    [Google Scholar]
  71. 71.
    Low A, Gavriilidis G, Larke N, BL MR, Drouin O et al. 2016. Incidence of opportunistic infections and the impact of antiretroviral therapy among HIV-infected adults in low- and middle-income countries: a systematic review and meta-analysis. Clin. Infect. Dis. 62:1595–603
    [Google Scholar]
  72. 72.
    Mansour MK, Yauch LE, Rottman JB, Levitz SM. 2004. Protective efficacy of antigenic fractions in mouse models of cryptococcosis. Infect. Immun. 72:1746–54
    [Google Scholar]
  73. 73.
    Marina CL, Burgel PH, Agostinho DP, Zamith-Miranda D, Las-Casas LO et al. 2020. Nutritional conditions modulate C. neoformans extracellular vesicles' capacity to elicit host immune response. Microorganisms 8:1815
    [Google Scholar]
  74. 74.
    Martinez-Lopez R, Nombela C, Diez-Orejas R, Monteoliva L, Gil C. 2008. Immunoproteomic analysis of the protective response obtained from vaccination with Candida albicans ecm33 cell wall mutant in mice. Proteomics 8:2651–64
    [Google Scholar]
  75. 75.
    Masso-Silva J, Espinosa V, Liu TB, Wang Y, Xue C, Rivera A. 2018. The F-Box protein Fbp1 shapes the immunogenic potential of Cryptococcus neoformans. mBio 9:e01828–17
    [Google Scholar]
  76. 76.
    Masur H, Ognibene FP, Yarchoan R, Shelhamer JH, Baird BF et al. 1989. CD4 counts as predictors of opportunistic pneumonias in human immunodeficiency virus (HIV) infection. Ann. Intern. Med. 111:223–31
    [Google Scholar]
  77. 77.
    Matthews RC, Burnie JP, Tabaqchali S. 1987. Isolation of immunodominant antigens from sera of patients with systemic candidiasis and characterization of serological response to Candida albicans. J. Clin. Microbiol. 25:230–37
    [Google Scholar]
  78. 78.
    McDermott AJ, Klein BS. 2018. Helper T-cell responses and pulmonary fungal infections. Immunology 155:155–63
    [Google Scholar]
  79. 79.
    Medici NP, Del Poeta M. 2015. New insights on the development of fungal vaccines: from immunity to recent challenges. Mem. Inst. Oswaldo Cruz 110:966–73
    [Google Scholar]
  80. 80.
    Miyagi K, Kawakami K, Kinjo Y, Uezu K, Kinjo T et al. 2005. CpG oligodeoxynucleotides promote the host protective response against infection with Cryptococcus neoformans through induction of interferon-gamma production by CD4+ T cells. Clin. Exp. Immunol. 140:220–29
    [Google Scholar]
  81. 81.
    Mizutani S, Endo M, Ino-Ue T, Kurasawa M, Uno Y et al. 2000. CD4+-T-cell-mediated resistance to systemic murine candidiasis induced by a membrane fraction of Candida albicans. Antimicrob. Agents Chemother. 44:2653–58
    [Google Scholar]
  82. 82.
    Nami S, Mohammadi R, Vakili M, Khezripour K, Mirzaei H, Morovati H. 2019. Fungal vaccines, mechanism of actions and immunology: a comprehensive review. Biomed. Pharmacother. 109:333–44
    [Google Scholar]
  83. 83.
    Nanjappa SG, Heninger E, Wuthrich M, Gasper DJ, Klein BS. 2012. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells. PLOS Pathog. 8:e1002771
    [Google Scholar]
  84. 84.
    Narra HP, Shubitz LF, Mandel MA, Trinh HT, Griffin K et al. 2016. A Coccidioides posadasiiCPS1 deletion mutant is avirulent and protects mice from lethal infection. Infect. Immun. 84:3007–16
    [Google Scholar]
  85. 85.
    Netea MG, Dominguez-Andres J, Barreiro LB, Chavakis T, Divangahi M et al. 2020. Defining trained immunity and its role in health and disease. Nat. Rev. Immunol 20375–88
  86. 86.
    Netea MG, Joosten LA, Latz E, Mills KH, Natoli G et al. 2016. Trained immunity: a program of innate immune memory in health and disease. Science 352:aaf1098
    [Google Scholar]
  87. 87.
    Normile TG, Rella A, Del Poeta M. 2021. Cryptococcus neoformans Δsgl1 vaccination requires either CD4+ or CD8+ T cells for complete host protection. Front. Cell. Infect. Microbiol. 11:739027
    [Google Scholar]
  88. 88.
    Oliveira LVN, Wang R, Specht CA, Levitz SM. 2021. Vaccines for human fungal diseases: close but still a long way to go. npj Vaccines 6:33
    [Google Scholar]
  89. 89.
    Pachl J, Svoboda P, Jacobs F, Vandewoude K, van der Hoven B et al. 2006. A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis. Clin. Infect. Dis 421404–13
  90. 90.
    Pappagianis D. 1993. Evaluation of the protective efficacy of the killed Coccidioides immitis spherule vaccine in humans: the Valley Fever Vaccine Study Group. Am. Rev. Respir. Dis. 148:656–60
    [Google Scholar]
  91. 91.
    Phair J, Munoz A, Detels R, Kaslow R, Rinaldo C, Saah A 1990. The risk of Pneumocystis carinii pneumonia among men infected with human immunodeficiency virus type 1: Multicenter AIDS Cohort Study Group. N. Engl. J. Med. 322:161–65
    [Google Scholar]
  92. 92.
    Phan QT, Myers CL, Fu Y, Sheppard DC, Yeaman MR et al. 2007. Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells. PLOS Biol. 5:e64
    [Google Scholar]
  93. 93.
    Pietrella D, Rachini A, Torosantucci A, Chiani P, Brown AJ et al. 2010. A beta-glucan-conjugate vaccine and anti-beta-glucan antibodies are effective against murine vaginal candidiasis as assessed by a novel in vivo imaging technique. Vaccine 28:1717–25
    [Google Scholar]
  94. 94.
    Pilon VA, Echols RM, Celo JS, Elmendorf SL. 1987. Disseminated Pneumocystis carinii infection in AIDS. N. Engl. J. Med. 316:1410–11
    [Google Scholar]
  95. 95.
    Plotkin S, Plotkin S 2013. A short history of vaccination. Vaccines S Plotkin, W Orenstein, P Offit 1–13 Cambridge, MA: Elsevier
    [Google Scholar]
  96. 96.
    Rachini A, Pietrella D, Lupo P, Torosantucci A, Chiani P et al. 2007. An anti-beta-glucan monoclonal antibody inhibits growth and capsule formation of Cryptococcus neoformans in vitro and exerts therapeutic, anticryptococcal activity in vivo. Infect. Immun. 75:5085–94
    [Google Scholar]
  97. 97.
    Rayens E, Rabacal W, Kang SE, Celia BN, Momany M, Norris KA. 2021. Vaccine-induced protection in two murine models of invasive pulmonary aspergillosis. Front. Immunol. 12:670578
    [Google Scholar]
  98. 98.
    Rella A, Mor V, Farnoud AM, Singh A, Shamseddine AA et al. 2015. Role of Sterylglucosidase 1 (Sgl1) on the pathogenicity of Cryptococcus neoformans: potential applications for vaccine development. Front. Microbiol. 6:836
    [Google Scholar]
  99. 99.
    Richie DL, Ghannoum MA, Isham N, Thompson KV, Ryder NS. 2012. Nonspecific effect of Mycograb on amphotericin B MIC. Antimicrob. Agents Chemother. 56:3963–64
    [Google Scholar]
  100. 100.
    Rivera A, Hohl TM. 2015. Calnexin bridges the gap toward a pan-fungal vaccine. Cell Host Microbe 17:421–23
    [Google Scholar]
  101. 101.
    Rizzo J, Chaze T, Miranda K, Roberson RW, Gorgette O et al. 2020. Characterization of extracellular vesicles produced by Aspergillus fumigatus protoplasts. mSphere 5:e00476–20
    [Google Scholar]
  102. 102.
    Rizzo J, Rodrigues ML, Janbon G. 2020. Extracellular vesicles in fungi: past, present, and future perspectives. Front. Cell. Infect. Microbiol. 10:346
    [Google Scholar]
  103. 103.
    Rodrigues ML, Nimrichter L, Oliveira DL, Frases S, Miranda K et al. 2007. Vesicular polysaccharide export in Cryptococcus neoformans is a eukaryotic solution to the problem of fungal trans-cell wall transport. Eukaryot. Cell 6:48–59
    [Google Scholar]
  104. 104.
    Rodrigues ML, Shi L, Barreto-Bergter E, Nimrichter L, Farias SE et al. 2007. Monoclonal antibody to fungal glucosylceramide protects mice against lethal Cryptococcus neoformans infection. Clin. Vaccine Immunol. 14:1372–76
    [Google Scholar]
  105. 105.
    Romani L. 2004. Immunity to fungal infections. Nat. Rev. Immunol. 4:11–24
    [Google Scholar]
  106. 106.
    Rosas AL, Nosanchuk JD, Casadevall A. 2001. Passive immunization with melanin-binding monoclonal antibodies prolongs survival of mice with lethal Cryptococcus neoformans infection. Infect. Immun. 69:3410–12
    [Google Scholar]
  107. 107.
    Roth MT, Zamith-Miranda D, Nosanchuk JD. 2019. Immunization strategies for the control of histoplasmosis. Curr. Trop. Med. Rep. 6:35–41
    [Google Scholar]
  108. 108.
    Saville SP, Lazzell AL, Chaturvedi AK, Monteagudo C, Lopez-Ribot JL. 2009. Efficacy of a genetically engineered Candida albicans tet-NRG1 strain as an experimental live attenuated vaccine against hematogenously disseminated candidiasis. Clin. Vaccine Immunol. 16:430–32
    [Google Scholar]
  109. 109.
    Schnizlein-Bick C, Durkin M, Kohler S, Connolly P, LeMonte A et al. 2003. Effects of CD4 and CD8 T lymphocyte depletion on the course of histoplasmosis following pulmonary challenge. Med. Mycol. 41:189–97
    [Google Scholar]
  110. 110.
    Shellito J, Suzara VV, Blumenfeld W, Beck JM, Steger HJ, Ermak TH. 1990. A new model of Pneumocystis carinii infection in mice selectively depleted of helper T lymphocytes. J. Clin. Investig. 85:1686–93
    [Google Scholar]
  111. 111.
    Singh VR, Smith DK, Lawerence J, Kelly PC, Thomas AR et al. 1996. Coccidioidomycosis in patients infected with human immunodeficiency virus: review of 91 cases at a single institution. Clin. Infect. Dis. 23:563–68
    [Google Scholar]
  112. 112.
    Siqueira IM, Wuthrich M, Li M, Wang H, Las-Casas LO et al. 2020. Early immune response against Fonsecaea pedrosoi requires Dectin-2-mediated Th17 activity, whereas Th1 response, aided by Treg cells, is crucial for fungal clearance in later stage of experimental chromoblastomycosis. PLOS Negl. Trop. Dis. 14:e0008386
    [Google Scholar]
  113. 113.
    Sparber F, LeibundGut-Landmann S. 2019. Interleukin-17 in antifungal immunity. Pathogens 8:54
    [Google Scholar]
  114. 114.
    Speakman EA, Dambuza IM, Salazar F, Brown GD. 2020. T cell antifungal immunity and the role of C-type lectin receptors. Trends Immunol. 41:61–76
    [Google Scholar]
  115. 115.
    Specht CA, Lee CK, Huang H, Hester MM, Liu J et al. 2017. Vaccination with recombinant Cryptococcus proteins in glucan particles protects mice against cryptococcosis in a manner dependent upon mouse strain and cryptococcal species. mBio 8:e01872–17
    [Google Scholar]
  116. 116.
    Specht CA, Lee CK, Huang H, Tipper DJ, Shen ZT et al. 2015. Protection against experimental cryptococcosis following vaccination with glucan particles containing Cryptococcus alkaline extracts. mBio 6:e01905–15
    [Google Scholar]
  117. 117.
    Specht CA, Nong S, Dan JM, Lee CK, Levitz SM. 2007. Contribution of glycosylation to T cell responses stimulated by recombinant Cryptococcus neoformans mannoprotein. J. Infect. Dis. 196:796–800
    [Google Scholar]
  118. 118.
    Spellberg B. 2011. Vaccines for invasive fungal infections. F1000 Med. Rep. 3:13
    [Google Scholar]
  119. 119.
    Spellberg B, Ibrahim AS, Yeaman MR, Lin L, Fu Y et al. 2008. The antifungal vaccine derived from the recombinant N terminus of Als3p protects mice against the bacterium Staphylococcus aureus. Infect. Immun. 76:4574–80
    [Google Scholar]
  120. 120.
    Spellberg BJ, Ibrahim AS, Avanesian V, Fu Y, Myers C et al. 2006. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J. Infect. Dis. 194:256–60
    [Google Scholar]
  121. 121.
    Spellberg BJ, Ibrahim AS, Avenissian V, Filler SG, Myers CL et al. 2005. The anti-Candida albicans vaccine composed of the recombinant N terminus of Als1p reduces fungal burden and improves survival in both immunocompetent and immunocompromised mice. Infect. Immun. 73:6191–93
    [Google Scholar]
  122. 122.
    Stott KE, Loyse A, Jarvis JN, Alufandika M, Harrison TS et al. 2021. Cryptococcal meningoencephalitis: time for action. Lancet Infect. Dis. 21:e259–71
    [Google Scholar]
  123. 123.
    Stuehler C, Khanna N, Bozza S, Zelante T, Moretti S et al. 2011. Cross-protective TH1 immunity against Aspergillus fumigatus and Candida albicans. Blood 117:5881–91
    [Google Scholar]
  124. 124.
    Sudbery PE. 2011. Growth of Candida albicans hyphae. Nat. Rev. Microbiol. 9:737–48
    [Google Scholar]
  125. 125.
    Taylor PR, Tsoni SV, Willment JA, Dennehy KM, Rosas M et al. 2007. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat. Immunol. 8:31–38
    [Google Scholar]
  126. 126.
    Thomas DP, Viudes A, Monteagudo C, Lazzell AL, Saville SP, Lopez-Ribot JL. 2006. A proteomic-based approach for the identification of Candida albicans protein components present in a subunit vaccine that protects against disseminated candidiasis. Proteomics 6:6033–41
    [Google Scholar]
  127. 127.
    Torosantucci A, Bromuro C, Chiani P, De Bernardis F, Berti F et al. 2005. A novel glyco-conjugate vaccine against fungal pathogens. J. Exp. Med. 202:597–606
    [Google Scholar]
  128. 128.
    Travassos LR, Taborda CP. 2017. Linear epitopes of Paracoccidioides brasiliensis and other fungal agents of human systemic mycoses as vaccine candidates. Front. Immunol. 8:224
    [Google Scholar]
  129. 129.
    Tso GHW, Reales-Calderon JA, Pavelka N. 2018. The elusive anti-Candida vaccine: lessons from the past and opportunities for the future. Front. Immunol. 9:897
    [Google Scholar]
  130. 130.
    Ueno K, Urai M, Sadamoto S, Shinozaki M, Takatsuka S et al. 2019. A dendritic cell-based systemic vaccine induces long-lived lung-resident memory Th17 cells and ameliorates pulmonary mycosis. Mucosal Immunol. 12:265–76
    [Google Scholar]
  131. 131.
    Uicker WC, McCracken JP, Buchanan KL. 2006. Role of CD4+ T cells in a protective immune response against Cryptococcus neoformans in the central nervous system. Med. Mycol. 44:1–11
    [Google Scholar]
  132. 132.
    Ulrich S, Ebel F. 2020. Monoclonal antibodies as tools to combat fungal infections. J. Fungi 6:22
    [Google Scholar]
  133. 133.
    Upadhya R, Baker LG, Lam WC, Specht CA, Donlin MJ, Lodge JK. 2018. Cryptococcus neoformans Cda1 and its chitin deacetylase activity are required for fungal pathogenesis. mBio 9:e02087–18
    [Google Scholar]
  134. 134.
    Upadhya R, Lam WC, Maybruck B, Specht CA, Levitz SM, Lodge JK. 2016. Induction of protective immunity to cryptococcal infection in mice by a heat-killed, chitosan-deficient strain of Cryptococcus neoformans. mBio 7:e01433–15
    [Google Scholar]
  135. 135.
    van de Veerdonk FL, Netea MG. 2010. T-cell subsets and antifungal host defenses. Curr. Fungal. Infect. Rep. 4:238–43
    [Google Scholar]
  136. 136.
    Vermitsky JP, Earhart KD, Smith WL, Homayouni R, Edlind TD, Rogers PD. 2006. Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and genome-wide expression studies. Mol. Microbiol. 61:704–22
    [Google Scholar]
  137. 137.
    Wang H, Lee TJ, Fites SJ, Merkhofer R, Zarnowski R et al. 2017. Ligation of Dectin-2 with a novel microbial ligand promotes adjuvant activity for vaccination. PLOS Pathog. 13:e1006568
    [Google Scholar]
  138. 138.
    Wang Y, Wang K, Masso-Silva JA, Rivera A, Xue C. 2019. A heat-killed Cryptococcus mutant strain induces host protection against multiple invasive mycoses in a murine vaccine model. mBio 10:e02145–19
    [Google Scholar]
  139. 139.
    Whibley N, Gaffen SL. 2014. Brothers in arms: Th17 and Treg responses in Candida albicans immunity. PLOS Pathog. 10:e1004456
    [Google Scholar]
  140. 140.
    Wisplinghoff H, Bischoff T, Tallent SM, Seifert H, Wenzel RP, Edmond MB. 2004. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin. Infect. Dis. 39:309–17
    [Google Scholar]
  141. 141.
    Wormley FL Jr., Perfect JR, Steele C, Cox GM. 2007. Protection against cryptococcosis by using a murine gamma interferon-producing Cryptococcus neoformans strain. Infect. Immun. 75:1453–62
    [Google Scholar]
  142. 142.
    Wozniak KL, Young ML, Wormley FL Jr. 2011. Protective immunity against experimental pulmonary cryptococcosis in T cell-depleted mice. Clin. Vaccine Immunol. 18:717–23
    [Google Scholar]
  143. 143.
    Wuthrich M, Brandhorst TT, Sullivan TD, Filutowicz H, Sterkel A et al. 2015. Calnexin induces expansion of antigen-specific CD4+ T cells that confer immunity to fungal ascomycetes via conserved epitopes. Cell. Host Microbe 17:452–65
    [Google Scholar]
  144. 144.
    Wuthrich M, Chang WL, Klein BS. 1998. Immunogenicity and protective efficacy of the WI-1 adhesin of Blastomyces dermatitidis. Infect. Immun. 66:5443–49
    [Google Scholar]
  145. 145.
    Wuthrich M, Deepe GS Jr., Klein B. 2012. Adaptive immunity to fungi. Annu. Rev. Immunol. 30:115–48
    [Google Scholar]
  146. 146.
    Wuthrich M, Filutowicz HI, Klein BS. 2000. Mutation of the WI-1 gene yields an attenuated Blastomyces dermatitidis strain that induces host resistance. J. Clin. Investig. 106:1381–89
    [Google Scholar]
  147. 147.
    Wuthrich M, Gern B, Hung CY, Ersland K, Rocco N et al. 2011. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J. Clin. Investig. 121:554–68
    [Google Scholar]
  148. 148.
    Xin H, Dziadek S, Bundle DR, Cutler JE. 2008. Synthetic glycopeptide vaccines combining beta-mannan and peptide epitopes induce protection against candidiasis. PNAS 105:13526–31
    [Google Scholar]
  149. 149.
    Yang YL, Wang CW, Chen CT, Wang MH, Hsiao CF, Lo HJ. 2009. Non-lethal Candida albicans cph1/cph1 efg1/efg1 mutant partially protects mice from systemic infections by lethal wild-type cells. Mycol. Res. 113:388–90
    [Google Scholar]
  150. 150.
    Zhai B, Wozniak KL, Masso-Silva J, Upadhyay S, Hole C et al. 2015. Development of protective inflammation and cell-mediated immunity against Cryptococcus neoformans after exposure to hyphal mutants. mBio 6:e01433–15
    [Google Scholar]
  151. 151.
    Zheng M, Ramsay AJ, Robichaux MB, Kliment C, Crowe C et al. 2005. CD4+ T cell-independent DNA vaccination against opportunistic infections. J. Clin. Investig. 115:3536–44
    [Google Scholar]
  152. 152.
    Zheng M, Shellito JE, Marrero L, Zhong Q, Julian S et al. 2001. CD4+ T cell-independent vaccination against Pneumocystis carinii in mice. J. Clin. Investig. 108:1469–74
    [Google Scholar]
  153. 153.
    Zhou P, Seder RA. 1998. CD40 ligand is not essential for induction of type 1 cytokine responses or protective immunity after primary or secondary infection with Histoplasma capsulatum. J. Exp. Med. 187:1315–24
    [Google Scholar]
  154. 154.
    Zhu Y, Yang C, Magee DM, Cox RA. 1996. Molecular cloning and characterization of Coccidioides immitis antigen 2 cDNA. Infect. Immun. 64:2695–99
    [Google Scholar]
/content/journals/10.1146/annurev-micro-041020-111511
Loading
/content/journals/10.1146/annurev-micro-041020-111511
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error