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一种合成肽疫苗可诱导免疫功能低下小鼠产生针对白色念珠菌感染的保护性免疫反应。

A synthetic peptide vaccine induces protective immune responses against Candida albicans infection in immunocompromised mice.

作者信息

Diez Ander, Arrieta-Aguirre Ines, Carrano Giulia, Bregón-Villahoz Marta, Moragues Maria-Dolores, Fernandez-de-Larrinoa Iñigo

机构信息

Department of Immunology, Microbiology and Parasitology, University of the Basque Country UPV/EHU, Leioa, Spain.

Department of Nursing I, University of the Basque Country UPV/EHU, Leioa, Spain.

出版信息

Vaccine. 2025 Apr 19;53:127102. doi: 10.1016/j.vaccine.2025.127102. Epub 2025 Apr 7.

Abstract

Invasive fungal infections, such as those caused by Candida species, predominantly affects hospitalized and immunocompromised patients. Current mortality rates are expected to rise as drug-resistant fungal species increase and the pool of immunocompromised individuals grows. Today, antifungal treatments show limited effectiveness, underscoring the need for new safe and effective antifungal vaccines. This study investigates the efficacy of a protective immunization strategy with DC stimulated by a synthetic peptide, 3P-KLH, containing epitopes from three Candida albicans proteins (Als3, Hwp1 and Met6) against a model of invasive candidiasis raised in immunosuppressed mice. Immunization effectively stimulated both humoral and cellular immune responses, as indicated by high antibody titers to the synthetic fungal peptide, increased cytokine levels, reduced fungal burden in kidneys and improved survival outcomes following infection. Although the variability in fungal burden in the control group limited the statistical significance for fungal clearance data, immunized mice showed a 64-fold lower fungal burden in renal tissues compared to controls. Cytokine analysis revealed elevated levels of IL-2, IL-17, and IFN-γ, suggesting a strong activation of Th1 and Th17 responses, both essential for antifungal immunity. Survival data further supported the protective effect of the immunogenic agent: 62.5 % immunized mice survived the 21-day post-infection period compared to 100 % mortality in controls. The progressively lower fungal burden over time in surviving mice suggests a sustained immune response that continues to suppress fungal replication. These results suggest that the immunization with the synthetic peptide stimulates a strong immune response, involving both antibody production and cell-mediated immunity, making it a promising candidate for therapeutic strategies against invasive candidiasis. Future work should focus on optimizing this immunization approach, assessing long-term immunity, and evaluating its potential in other fungal infection models.

摘要

侵袭性真菌感染,如由念珠菌属引起的感染,主要影响住院患者和免疫功能低下的患者。随着耐药真菌种类的增加以及免疫功能低下个体数量的增多,目前的死亡率预计会上升。如今,抗真菌治疗效果有限,这凸显了新型安全有效的抗真菌疫苗的必要性。本研究调查了用含有来自三种白色念珠菌蛋白(Als3、Hwp1和Met6)表位的合成肽3P-KLH刺激的树突状细胞进行保护性免疫策略,对免疫抑制小鼠中建立的侵袭性念珠菌病模型的疗效。免疫有效刺激了体液免疫和细胞免疫反应,表现为针对合成真菌肽的高抗体滴度、细胞因子水平升高、肾脏中真菌负荷降低以及感染后生存结果改善。尽管对照组中真菌负荷的变异性限制了真菌清除数据的统计学显著性,但与对照组相比,免疫小鼠肾组织中的真菌负荷低64倍。细胞因子分析显示IL-2、IL-17和IFN-γ水平升高,表明Th1和Th17反应强烈激活,这两者对于抗真菌免疫都至关重要。生存数据进一步支持了免疫原性制剂的保护作用:62.5%的免疫小鼠在感染后21天存活,而对照组的死亡率为100%。存活小鼠中随着时间推移真菌负荷逐渐降低,表明持续的免疫反应持续抑制真菌复制。这些结果表明,用合成肽免疫可刺激强烈的免疫反应,包括抗体产生和细胞介导的免疫,使其成为侵袭性念珠菌病治疗策略的有希望的候选者。未来的工作应集中在优化这种免疫方法、评估长期免疫力以及评估其在其他真菌感染模型中的潜力。

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