{"title":"Dual-antigen fusion protein vaccination induces protective immunity against <i>Candida albicans</i> infection in mice.","authors":"Keran Jia, Yanhao Zhang, Mengyu Jiang, Mengge Cui, Jia Wang, Jiajia Zhang, Hua Wang, Huihai Zhao, Mengyan Li, Quanming Zou, Hao Zeng","doi":"10.1080/21645515.2024.2406065","DOIUrl":null,"url":null,"abstract":"<p><p><i>Candida albicans</i> 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 <i>C. albicans</i>, using AlPO<sub>4</sub> as an adjuvant. The AH vaccine was constructed by fusing Als3<sub>17-432</sub> and Hyr1<sub>25-350</sub> 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 AlPO<sub>4</sub>, followed by a lethal challenge with <i>C. albicans</i> 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-AlPO<sub>4</sub> combination exhibited significantly higher antibody titers, particularly IgG and its subclasses, compared to controls (<i>p</i> < .001). The survival rate of vaccinated mice was 80% post-infection, significantly higher than the control group (<i>p</i> < .01). Vaccinated mice showed reduced fungal loads in the blood, kidneys, spleen, and liver (<i>p</i> < .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 (<i>p</i> < .05). Rabbit serum with polyclonal antibodies demonstrated effective antifungal activity, confirming vaccine efficacy across species. The AH-AlPO<sub>4</sub> vaccine effectively induced strong immune responses, reduced fungal burden, and protected against organ pathology in <i>C. albicans</i> infections. These findings support further development of dual-antigen vaccine strategies.</p>","PeriodicalId":49067,"journal":{"name":"Human Vaccines & Immunotherapeutics","volume":"20 1","pages":"2406065"},"PeriodicalIF":4.1000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441037/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Vaccines & Immunotherapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/21645515.2024.2406065","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/9/26 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
(formerly Human Vaccines; issn 1554-8619)
Vaccine research and development is extending its reach beyond the prevention of bacterial or viral diseases. There are experimental vaccines for immunotherapeutic purposes and for applications outside of infectious diseases, in diverse fields such as cancer, autoimmunity, allergy, Alzheimer’s and addiction. Many of these vaccines and immunotherapeutics should become available in the next two decades, with consequent benefit for human health. Continued advancement in this field will benefit from a forum that can (A) help to promote interest by keeping investigators updated, and (B) enable an exchange of ideas regarding the latest progress in the many topics pertaining to vaccines and immunotherapeutics.
Human Vaccines & Immunotherapeutics provides such a forum. It is published monthly in a format that is accessible to a wide international audience in the academic, industrial and public sectors.