Khan Masood Alam, Mousa Ayman M, Alradhi Arwa Essa, Allemailem Khaled
Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia.
Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraidah 51452, Saudi Arabia.
Life Sci. 2025 Jan 15;361:123312. doi: 10.1016/j.lfs.2024.123312. Epub 2024 Dec 12.
Vulvovaginal candidiasis (VVC) is a common women's health issue, with rising antifungal resistance. This study was aimed to prepare and evaluate the efficacy of a lipid nanoparticle-based vaccine in a murine model of VVC.
Dried and reconstituted vesicles containing C. albicans antigens (DRNPs-Ca-Ags) vaccine, formulated with phosphatidylcholine and cholesterol-based lipid nanoparticles via film hydration and freeze-drying. The safety evaluation of DRNPs-CaAgs was conducted by determining hepatic (AST, ALT) or renal (BUN, creatinine) biomarkers. Female mice were immunized with DRNPs-CaAgs or Alum-CaAgs, and immune responses were evaluated via antibody titers, IgG isotypes, and splenocyte proliferation. Protective efficacy of vaccine formulations was assessed through fungal burden, biofilm formation, cytokine levels, and histopathological analysis of vaginal tissues.
Mice vaccinated with DRNPs-CaAgs showed significantly enhanced immune responses, with higher antibody titers and IgG2a levels as compared to the Alum-CaAgs group. Vaginal fungal burden was dramatically reduced (665 ± 78 CFUs in DRNPs-CaAgs immunized group vs. 12,944 ± 3540 CFUs in Alum-CaAgs group, p < 0.01). Biofilm formation decreased by 45 % (p < 0.05), and inflammatory cytokines were significantly lowered. Histopathological analysis revealed minimal tissue damage in DRNPs-CaAgs vaccinated mice.
The findings suggest DRNPs-CaAgs as a promising vaccine for VVC, eliciting strong immunity, reducing fungal load, and minimizing inflammation. While the reliance on a murine model is a limitation, future clinical trials are essential to evaluate its efficacy and safety in humans, offering a potential strategy to combat drug-resistant infections and improve women's reproductive health.
外阴阴道念珠菌病(VVC)是一个常见的女性健康问题,且抗真菌耐药性不断上升。本研究旨在制备一种基于脂质纳米颗粒的疫苗,并在VVC小鼠模型中评估其疗效。
含有白色念珠菌抗原的干燥复溶囊泡(DRNPs-Ca-Ags)疫苗,通过薄膜水化和冷冻干燥,用磷脂酰胆碱和胆固醇基脂质纳米颗粒配制而成。通过测定肝脏(AST、ALT)或肾脏(BUN、肌酐)生物标志物对DRNPs-CaAgs进行安全性评估。用DRNPs-CaAgs或明矾-白色念珠菌抗原(Alum-CaAgs)对雌性小鼠进行免疫,并通过抗体滴度、IgG亚型和脾细胞增殖评估免疫反应。通过真菌负荷、生物膜形成、细胞因子水平和阴道组织的组织病理学分析评估疫苗制剂的保护效果。
与Alum-CaAgs组相比,接种DRNPs-CaAgs的小鼠免疫反应显著增强,抗体滴度和IgG2a水平更高。阴道真菌负荷显著降低(DRNPs-CaAgs免疫组为665±78 CFU,而Alum-CaAgs组为12,944±3540 CFU,p<0.01)。生物膜形成减少了45%(p<0.05),炎症细胞因子显著降低。组织病理学分析显示,接种DRNPs-CaAgs的小鼠组织损伤最小。
研究结果表明DRNPs-CaAgs是一种有前景的VVC疫苗,可引发强大的免疫力,降低真菌负荷,并将炎症降至最低。虽然依赖小鼠模型是一个局限性,但未来的临床试验对于评估其在人类中的疗效和安全性至关重要,为对抗耐药性感染和改善女性生殖健康提供了一种潜在策略。