Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice

Candida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH)...

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Main Authors: Keran Jia, Yanhao Zhang, Mengyu Jiang, Mengge Cui, Jia Wang, Jiajia Zhang, Hua Wang, Huihai Zhao, Mengyan Li, Quanming Zou, Hao Zeng
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Human Vaccines & Immunotherapeutics
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Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2024.2406065
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author Keran Jia
Yanhao Zhang
Mengyu Jiang
Mengge Cui
Jia Wang
Jiajia Zhang
Hua Wang
Huihai Zhao
Mengyan Li
Quanming Zou
Hao Zeng
author_facet Keran Jia
Yanhao Zhang
Mengyu Jiang
Mengge Cui
Jia Wang
Jiajia Zhang
Hua Wang
Huihai Zhao
Mengyan Li
Quanming Zou
Hao Zeng
author_sort Keran Jia
collection DOAJ
description Candida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of C. albicans, using AlPO4 as an adjuvant. The AH vaccine was constructed by fusing Als317-432 and Hyr125-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO4, followed by a lethal challenge with C. albicans SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine’s efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO4 combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (p < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (p < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (p < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (p < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO4 vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in C. albicans infections. These findings support further development of dual-antigen vaccine strategies.
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spelling doaj-art-137ff19e11774d048fb72bfb8ec1d5922025-08-20T02:34:20ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2024.2406065Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in miceKeran Jia0Yanhao Zhang1Mengyu Jiang2Mengge Cui3Jia Wang4Jiajia Zhang5Hua Wang6Huihai Zhao7Mengyan Li8Quanming Zou9Hao Zeng10National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, ChinaNational Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, ChinaDepartment of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, ChinaDepartment of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, ChinaDepartment of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, ChinaDepartment of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, ChinaDepartment of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, ChinaDepartment of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, ChinaDepartment of Clinical Laboratory, The 980th Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital), Shijiazhuang, ChinaNational Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, ChinaNational Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, ChinaCandida albicans Is a leading cause of nosocomial bloodstream infections, particularly in immunocompromised patients. Current therapeutic strategies are insufficient, highlighting the need for effective vaccines. This study aimed to evaluate the efficacy of a dual-antigen fusion protein vaccine (AH) targeting the Als3 and Hyr1 proteins of C. albicans, using AlPO4 as an adjuvant. The AH vaccine was constructed by fusing Als317-432 and Hyr125-350 proteins, and its immunogenicity was tested in BALB/c mice and New Zealand white rabbits. Mice received three intramuscular doses of the vaccine combined with AlPO4, followed by a lethal challenge with C. albicans SC5314. Survival rates, antibody responses, cytokine production, fungal burdens, and organ pathology were assessed. The vaccine’s efficacy was also validated using rabbit serum. Mice vaccinated with the AH-AlPO4 combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (p < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (p < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (p < .05). Increased levels of interferon gamma and interleukin (IL)-17A were observed, indicating robust T helper (Th) 1 and Th17 cell responses. Vaccination mitigated organ damage, with kidney and liver pathology scores significantly lower than those of unvaccinated mice (p < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO4 vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in C. albicans infections. These findings support further development of dual-antigen vaccine strategies.https://www.tandfonline.com/doi/10.1080/21645515.2024.2406065Candida albicans vaccinedual-antigen fusion protein (AH)antifungal efficacyhumoral immune responserabbit models
spellingShingle Keran Jia
Yanhao Zhang
Mengyu Jiang
Mengge Cui
Jia Wang
Jiajia Zhang
Hua Wang
Huihai Zhao
Mengyan Li
Quanming Zou
Hao Zeng
Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice
Human Vaccines & Immunotherapeutics
Candida albicans vaccine
dual-antigen fusion protein (AH)
antifungal efficacy
humoral immune response
rabbit models
title Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice
title_full Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice
title_fullStr Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice
title_full_unstemmed Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice
title_short Dual-antigen fusion protein vaccination induces protective immunity against Candida albicans infection in mice
title_sort dual antigen fusion protein vaccination induces protective immunity against candida albicans infection in mice
topic Candida albicans vaccine
dual-antigen fusion protein (AH)
antifungal efficacy
humoral immune response
rabbit models
url https://www.tandfonline.com/doi/10.1080/21645515.2024.2406065
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