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

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-04-07 DOI:10.1016/j.vaccine.2025.127102

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

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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.

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合成肽疫苗诱导免疫功能低下小鼠对白色念珠菌感染的保护性免疫反应

侵袭性真菌感染，如由念珠菌引起的感染，主要影响住院和免疫功能低下的患者。随着耐药真菌种类的增加和免疫功能受损个体的增加，目前的死亡率预计会上升。今天，抗真菌治疗显示出有限的效果，强调需要新的安全有效的抗真菌疫苗。本研究研究了一种由合成肽3P-KLH刺激DC的保护性免疫策略的有效性，该肽含有来自三种白色念珠菌蛋白（Als3， Hwp1和Met6）的表位，可抑制免疫抑制小鼠的侵袭性念珠菌病模型。免疫有效地刺激了体液和细胞免疫反应，正如对合成真菌肽的高抗体滴度所表明的那样，增加了细胞因子水平，减少了肾脏的真菌负担，改善了感染后的生存结果。尽管对照组真菌负荷的可变性限制了真菌清除数据的统计学意义，但免疫小鼠的肾组织真菌负荷比对照组低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反应被强烈激活，这两种反应都是抗真菌免疫所必需的。存活数据进一步支持免疫原性药物的保护作用：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%。随着时间的推移，存活小鼠的真菌负担逐渐降低，这表明持续的免疫反应继续抑制真菌复制。这些结果表明，合成肽免疫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物。未来的工作应侧重于优化这种免疫方法，评估长期免疫，并评估其在其他真菌感染模型中的潜力。

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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