{"title":"双抗原融合蛋白疫苗接种可诱导小鼠对白色念珠菌感染产生保护性免疫。","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":"{\"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}","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
摘要
白色念珠菌是引起院内血流感染的主要原因,尤其是在免疫力低下的患者中。目前的治疗策略并不充分,因此需要有效的疫苗。本研究旨在以 AlPO4 为佐剂,评估针对白僵菌 Als3 和 Hyr1 蛋白的双抗原融合蛋白疫苗(AH)的疗效。AH疫苗由Als317-432和Hyr125-350蛋白融合而成,其免疫原性在BALB/c小鼠和新西兰白兔中进行了测试。小鼠肌肉注射了三剂与 AlPO4 结合的疫苗,随后接受了白僵菌 SC5314 的致命挑战。对小鼠的存活率、抗体反应、细胞因子产生、真菌负担和器官病理学进行了评估。此外,还使用兔血清验证了疫苗的有效性。与对照组相比,接种 AH-AlPO4 组合疫苗的小鼠表现出明显更高的抗体滴度,尤其是 IgG 及其亚类(p p p p 4 疫苗能有效诱导强烈的免疫反应,减少真菌负担,并防止白僵菌感染引起的器官病变。这些发现为进一步开发双抗原疫苗策略提供了支持。
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) 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.