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Cited by 162Antifungal resistance and susceptibilityFungal Infections and StudiesFungal and yeast genetics research

The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection

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Singh, Shakti, Uppuluri, Priya, Mamouei, Zeinab, Alqarihi, Abdullah, Elhassan, Hana, French, Samuel, Lockhart, Shawn R., Chiller, Tom +2 more·2019·PLOS Pathogens
DOI 10.1371/journal.ppat.1007460PMC PMC6695204

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Abstract

Abstract Candida auris is an emerging, multi-drug resistant, health care-associated fungal pathogen. Its predominant prevalence in hospitals and nursing homes indicates its ability to adhere to and colonize the skin, or persist in an environment outside the host - a trait unique from other Candida species. Besides being associated globally with life-threatening disseminated infections, C. auris also poses significant clinical challenges due to its ability to adhere to polymeric surfaces and form highly drug-resistant biofilms. Here, we performed bioinformatic studies to identify the presence of adhesin proteins in C. auris , with sequence as well as 3-D structural homologies to the major adhesin/invasin of C. albicans , Als3. Anti-Als3p antibodies generated by vaccinating mice with NDV-3A (a vaccine based on the N-terminus of Als3 protein formulated with alum) recognized C. auris in vitro , blocked its ability to form biofilms and enhanced macrophage-mediated killing of the fungus. Furthermore, NDV-3A vaccination induced significant levels of C. auris cross-reactive humoral and cellular immune responses, and protected immunosuppressed mice from lethal C. auris disseminated infection, compared to the control alum-vaccinated mice. Finally, NDV-3A potentiated the protective efficacy of the antifungal drug micafungin, against C. auris candidemia. Identification of Als3-like adhesins in C. auris makes it a target for immunotherapeutic strategies using NDV-3A, a vaccine with known efficacy against other Candida species and safety as well as efficacy in clinical trials. Considering that C. auris can be resistant to almost all classes of antifungal drugs, such an approach has profound clinical relevance. Author Summary Candida auris has emerged as a major health concern to hospitalized patients and nursing home subjects. C. auris strains display multidrug resistance to current antifungal therapy and cause lethal infections. We have determined that C. auris harbors homologs of C. albicans Als cell surface proteins. The C. albicans NDV-3A vaccine, harboring the N-terminus of Als3p formulated with alum, generates cross-reactive antibodies against C. auris clinical isolates and protects neutropenic mice from hematogenously disseminated C. auris infection. Importantly, the NDV-3A vaccine displays an additive protective effect in neutropenic mice when combined with micafungin. Due to its proven safety and efficacy in humans against C. albicans infection, our studies support the expedited testing of the NDV-3A vaccine against C. auris in future clinical trials.

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  • Anti-Als3 antibodies generated by the NDV-3A vaccine target ALS adhesin proteins on the C. auris surface, disrupting adhesion, biofilm formation, and opsonophagocytic killing.

    “Anti-Als3 protein antibodies, generated in response to the vaccine containing the N-terminal region of C. albicans Als3 protein, specifically target ALS adhesin proteins on the C. auris surface, resulting in disruption of adhesion, biofilm formation, and opsonophagocytic killing30.”

    From Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins (2025) · cites this paper as [30]

    The Results sections on antibody binding and biofilms show that NDV-3A-induced anti-Als3p antibodies bind C. auris surface homologs and that vaccinated-mouse sera inhibit biofilm formation. The paper does not separately demonstrate disrupted adhesion, and its Results say the antibodies enhance—not disrupt—opsonophagocytic killing. Page numbers are unavailable in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • C. auris displays at least three Als-like, eight Hyr/Iff-like, and one species-specific adhesin (Scf1).

    “C. auris displays at least three Als-like, eight Hyr/Iff-like, and one species-specific adhesin (Scf1) (27, 53–55) (Table S3).”

    From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [54]

    The Results section (‘C. auris possesses homologs of C. albicans Als3’; page unavailable) identifies three C. auris proteins homologous to Als3p, supporting the Als-like count. The cited paper does not establish the claimed eight Hyr/Iff-like adhesins or the species-specific adhesin Scf1; those parts of the sentence are not supported by this source. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • NDV-3A protects mice from disseminated C. auris infection.

    “Recent evidence suggests that NDV-3A (a vaccine based on the N-terminus of Als3 protein formulated with alum) protects mice from disseminated C. auris infection, although its role in protecting against skin C. auris infection remains unclear [42].”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [42]

  • The role of NDV-3A in protecting against skin C. auris infection remains unclear.

    “Recent evidence suggests that NDV-3A (a vaccine based on the N-terminus of Als3 protein formulated with alum) protects mice from disseminated C. auris infection, although its role in protecting against skin C. auris infection remains unclear [42].”

    From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [42]

  • NDV-3A vaccination significantly improves protection of mice against hematogenous disseminated C. auris infections.

    “NDV-3A vaccination significantly improves the protection of mice against hematogenous disseminated C. auris infections30.”

    From Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins (2025) · cites this paper as [30]

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Research works printed but not linked: 39

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Authors
Singh, S., Uppuluri, P., Mamouei, Z., Alqarihi, A., Elhassan, H., French, S., Lockhart, S. R., Chiller, T., Edwards, J. E., & Ibrahim, A. S.
Affiliations
  • University of California, Los Angeles (US)
  • Centers for Disease Control and Prevention (US)
Corresponding author
Ibrahim, Ashraf S.
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2019-08-05
Volume
15
Issue
8
Pages
e1007460
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1007460
PMC
PMC6695204
OpenAlex
W2965402820
Cited by
162
References
8
Citations by year
2026: 23 · 2025: 29 · 2024: 17 · 2023: 25 · 2022: 30 · 2021: 20 · 2020: 14 · 2019: 4
FWCI
13.03
Type
journal article
Language
en
Update notices
new_version (2019-08-15)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, public-domain)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion, public-domain)
  • Figshare (submittedVersion, cc-by)
Funders
National Institute of Allergy and Infectious Diseases (AI063382, R01AI141202)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Candida auris, antifungal vaccines, multidrug resistance, biofilm formation, macrophage-mediated killing, CD4+ T helper cells, candidemia, disseminated fungal infection, immunotherapy
MeSH terms
Alum Compounds, Animals, Candida, Candidiasis, Fungal Proteins, Fungal Vaccines, Mice, Inbred ICR, Vaccination, CD4-Positive T-Lymphocytes, Drug Resistance, Multiple, Biofilms, Mice

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