Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity

Ibrahim, Ashraf S.; Spellberg, Brad J.; Avenissian, Valentina; Fu, Yue; Filler, Scott G.; Edwards, John E.

doi:10.1128/iai.73.2.999-1005.2005

Cited by 83Antifungal resistance and susceptibilityFungal Infections and StudiesFungal and yeast genetics research

Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity

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Ibrahim, Ashraf S., Spellberg, Brad J., Avenissian, Valentina, Fu, Yue, Filler, Scott G., Edwards, John E.·2005·Infection and Immunity

DOI 10.1128/iai.73.2.999-1005.2005PMC PMC547099

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Abstract

Candida spp. are opportunistic fungal pathogens that are among the most common causes of nosocomial bloodstream infections. The mortality attributable to disseminated candidiasis is 40 to 50% despite antifungal therapy. Clearly, new strategies are needed to prevent this life-threatening infection. Because risk factors for disseminated candidiasis are well defined and frequently of limited duration, vaccination is an appealing prophylactic strategy. We have identified a cell surface protein, Als1p, that mediates adherence of Candida albicans to a variety of human substrates and plastic. Here we report that immunizing BALB/c mice with the recombinant N-terminal domain of Als1p (rAls1p-N) improved survival during a subsequent challenge with a lethal inoculum of C. albicans. The protective 20-μg dose of rAls1p-N significantly increased Candida stimulation of Th1 splenocytes and increased in vivo delayed-type hypersensitivity. In contrast, antibody titers did not correlate with protection. Finally, the vaccine was not protective in T-cell-deficient mice but was protective in B-cell-deficient mice. These data indicate that the mechanism of action of the rAls1p-N vaccine is stimulation of cell-mediated, rather than humoral, immunity against C. albicans. The majority of efforts to date have focused on the development of passive immunization strategies to prevent or treat disseminated candidiasis. In contrast, our results provide proof of principle for vaccination with an adhesin of C. albicans and emphasize the potential for cell-mediated immune modulation as a prophylactic or therapeutic strategy against disseminated candidiasis.

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No fungal vaccine has been approved for humans.
“However, no fungal vaccine has been approved for humans [17,41].”
From The Emerging Fungal Pathogen Candida auris Induces IFNγ to Colonize the Skin (2025) · cites this paper as [41]

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The Anti-Candida Vaccine Based on the Recombinant N-Terminal Domain of Als1p Is Broadly Active against Disseminated Candidiasis
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Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity. Infect. Immun
Ibrahim, A. S., Spellberg, B. J., Avenissian, V., Fu, Y., Filler, S. G., & Edwards, J. E. (2005)
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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
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Efficacy of the Anti-Candida rAls3p-N or rAls1p-N Vaccines against Disseminated
Candidiasis, M., Spellberg, B. J., Ibrahim, A. S., Avanesian, V., Fu, Y., Myers, C. L., Phan, Q. T., Filler, S. G., Yeaman, M. R., & Edwards, J. E. (2006)
Self-citation

Authors: Ibrahim, A. S., Spellberg, B. J., Avenissian, V., Fu, Y., Filler, S. G., & Edwards, J. E.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Ibrahim, Ashraf S.
ORCID: Ibrahim, Ashraf S.
Spellberg, Brad J.
Fu, Yue
Filler, Scott G.
Edwards, John E.
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2005-02
Volume: 73
Issue: 2
Pages: 999-1005
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.73.2.999-1005.2005
PMC: PMC547099
OpenAlex: W2122999031
Cited by: 83
References: 68
Citations by year: 2025: 3 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 10 · 2013: 1 · 2012: 3
FWCI: 6.21
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Allergy and Infectious Diseases (P01 AI-37194, R01AI019990, R03AI054531, K08AI060641, R01AI054928, R03 AI 054331, P01AI037194)
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 albicans, systemic candidiasis, recombinant vaccine, cell-mediated immunity, Th1 response, delayed-type hypersensitivity, adhesins, fungal adhesion, humoral immunity, T cell deficiency, B cell deficiency, prophylactic vaccination, fungemia
MeSH terms: Animals, Antibodies, Antibody Formation, Candida albicans, Candidiasis, Fungal Proteins, Hypersensitivity, Delayed, Immunity, Cellular, Peptide Fragments, Recombinant Proteins, Time Factors, Vaccination, Protein Structure, Tertiary, Th1 Cells, Mice

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Vaccination with recombinant N-terminal domain of Als1p improves survival during murine disseminated candidiasis by enhancing cell-mediated, not humoral, immunity

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