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Cited by 135Antifungal resistance and susceptibilityFungal Infections and StudiesImmune responses and vaccinations

The DOI matches its Crossref record; 85 of the 86 references it cites were found in a registry or an index.

Vaccines for human fungal diseases: close but still a long way to go

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Oliveira, Lorena V. N., Wang, Ruiying, Specht, Charles A., Levitz, Stuart M.·2021·npj Vaccines
DOI 10.1038/s41541-021-00294-8PMC PMC7930017
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Abstract

Despite the substantial global burden of human fungal infections, there are no approved fungal vaccines to protect at risk individuals. Here, we review the progress that has been made and the challenges that lie ahead in the quest towards efficacious fungal vaccines. In mouse studies, protection has been achieved with vaccines directed against fungal pathogens, including species of Candida, Cryptococcus , and Aspergillus , that most commonly cause life-threatening human disease. Encouraging results have been obtained with vaccines composed of live-attenuated and killed fungi, crude extracts, recombinant subunit formulations, and nucleic acid vaccines. Novel adjuvants that instruct the immune system to mount the types of protective responses needed to fight mycotic infections are under development. Candidate vaccines include those that target common antigens expressed on multiple genera of fungi thereby protecting against a broad range of mycoses. Encouragingly, three vaccines have reached human clinical trials. Still, formidable obstacles must be overcome before we will have fungal vaccines licensed for human use.

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Fig. 1 Schematic model of the fungal cell wall. This model shows the three basic components of the cell wall present in almost all fungal pathogens. Mannoproteins have polymers of mannose that decorate the proteins through O-linkages or N-linkages and are predominately found in the outer portion of cell wall. β-glucans are the most abundant constituent of the cell wall and tend to be in the middle with β-1,3-glucans forming the scaffold and β-1,6-glucans forming the branches, while chitin is found in the inner portion of the cell wall and linked to β-1,3-glucan. Other components of the cell wall in some fungi include α-glucan, galactomannan, chitosan, and melanin. In addition, the cryptococcal capsule is linked to the cell wall. Figure created with BioRender.com.
Fig. 1 Schematic model of the fungal cell wall. This model shows the three basic components of the cell wall present in almost all fungal pathogens. Mannoproteins have polymers of mannose that decorate the proteins through O-linkages or N-linkages and are predominately found in the outer portion of cell wall. β-glucans are the most abundant constituent of the cell wall and tend to be in the middle with β-1,3-glucans forming the scaffold and β-1,6-glucans forming the branches, while chitin is found in the inner portion of the cell wall and linked to β-1,3-glucan. Other components of the cell wall in some fungi include α-glucan, galactomannan, chitosan, and melanin. In addition, the cryptococcal capsule is linked to the cell wall. Figure created with BioRender.com.CC BY · PubMed Central
Fig. 2 Examples of the diversity in fungal morphology in human tissue from patients with mycoses. a Tissue Gram stain of C. albicans from a patient with endocarditis. Hyphae (elongated cells), pseudo-hyphae (sausage-shaped cells) and yeasts (oval cells, some with buds) stain deep purple. Candida cells average 2–8 microns in diameter. b Mucicarmine stain of C. neoformans in the lungs of a patient with pulmonary cryptococcosis. Budding yeast cells with capsules that stain rose red are present. Yeast cells average about 5 microns in diameter without capsule. Capsular thickness is variable, typically ranging from 1 to 10 microns. c Grocott’s methenamine silver stain of A. fumigatus from a patient with invasive pulmonary aspergillosis. Septate hyphae with “Y”-shaped branching that stain silvery black are present. Average hyphal diameter is about 3 microns. d Periodic acid-Schiff stain of C. immitis from a patient with coccidioidomycosis. Three spherules, each containing endospores, are present. Spherules and endospores range in diameter from 10 to 100 microns and 2 to 5 microns, respectively. A single spherule can contain hundreds of endospores. Photo image credits. a, b, and d: Centers for Disease Control Public Health Image Library. c: Wikimedia Commons.
Fig. 2 Examples of the diversity in fungal morphology in human tissue from patients with mycoses. a Tissue Gram stain of C. albicans from a patient with endocarditis. Hyphae (elongated cells), pseudo-hyphae (sausage-shaped cells) and yeasts (oval cells, some with buds) stain deep purple. Candida cells average 2–8 microns in diameter. b Mucicarmine stain of C. neoformans in the lungs of a patient with pulmonary cryptococcosis. Budding yeast cells with capsules that stain rose red are present. Yeast cells average about 5 microns in diameter without capsule. Capsular thickness is variable, typically ranging from 1 to 10 microns. c Grocott’s methenamine silver stain of A. fumigatus from a patient with invasive pulmonary aspergillosis. Septate hyphae with “Y”-shaped branching that stain silvery black are present. Average hyphal diameter is about 3 microns. d Periodic acid-Schiff stain of C. immitis from a patient with coccidioidomycosis. Three spherules, each containing endospores, are present. Spherules and endospores range in diameter from 10 to 100 microns and 2 to 5 microns, respectively. A single spherule can contain hundreds of endospores. Photo image credits. a, b, and d: Centers for Disease Control Public Health Image Library. c: Wikimedia Commons.CC BY · PubMed Central

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Show all 86 references

Research works printed but not linked: 3

  1. Rizzo, J. et al. New insights into Cryptococcus extracellular vesicles suggest a new structural model and an antifungal vaccine strategy. Preprint at bioRxiv https://doi.org/10.1101/2020.08.17.253716 (2020). · DOI
  2. Hester, M. M. et al. Protection of mice against experimental cryptococcosis using glucan particle-based vaccines containing novel recombinant antigens. Vaccine https://doi.org/10.1016/j.vaccine.2019.10.051 (2019). · DOI
  3. Levitz, S. M. Aspergillus vaccines: Hardly worth studying or worthy of hard study? Med. Mycol. 55, 103–108 (2017). · DOI

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Metadata

Authors
Oliveira, L. V. N., Wang, R., Specht, C. A., & Levitz, S. M.
Affiliations
University of Massachusetts Chan Medical School (US)
Corresponding author
Levitz, Stuart M.
ORCID
Venue
npj Vaccines
Publisher
Springer Science and Business Media LLC
Published
2021-03-03
Volume
6
Issue
1
Pages
33-33
ISSN
2059-0105 (ISSN-L)
DOI
10.1038/s41541-021-00294-8
PMC
PMC7930017
OpenAlex
W3134624653
Cited by
135
References
86
Citations by year
2026: 12 · 2025: 25 · 2024: 31 · 2023: 23 · 2022: 40 · 2021: 4
FWCI
2.87
Type
journal article
Language
en
Open access
Licence
Locations
  • npj Vaccines (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship@UMassChan (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Division of Intramural Research, National Institute of Allergy and Infectious Diseases (AI125045)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
fungal vaccines, human fungal infections, Candida, Cryptococcus, Aspergillus, recombinant subunit vaccine, nucleic acid vaccines, vaccine adjuvants, clinical trials, vaccine development

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