CpG 佐剂病毒样颗粒疫苗可诱导针对唐氏利什曼原虫感染的保护性免疫力

Keon-Woong Yoon, Ki Back Chu, Gi-Deok Eom, Jie Mao, Eun-Kyung Moon, Sung Soo Kim, Fu-Shi Quan
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摘要

由于缺乏已获批准的人类疫苗,内脏利什曼病(VL)对公共卫生构成了重大挑战。我们试图通过CpG寡脱氧核苷酸(CpG-ODN)佐剂来提高表达唐氏利什曼原虫表面抗原的病毒样颗粒疫苗(LdPSA-VLP)的效力。在此,我们评估了佐剂疫苗诱导的免疫反应及其在小鼠体内对表达 mCherry 的唐诺瓦尼原鞭毛虫的免疫效果。佐剂 LdPSA-VLP 疫苗接种能显著提高寄生虫特异性 IgG、IgG1、IgG2a 和 IgG2b 血清抗体水平。此外,与未接种疫苗的小鼠相比,接种疫苗的小鼠生殖中心 B 细胞和脾脏 T 细胞活性增强。重要的是,佐剂 LdPSA-VLPs 降低了内脏器官中炎症细胞因子 IFN-γ 和 IL-6 的水平,从而减少了寄生虫的总负荷,保护小鼠免受唐诺瓦尼氏菌的侵袭。我们的研究结果表明,CpG-ODN增强了LdPSA-VLPs的保护作用,为有效开发VL疫苗迈出了充满希望的一步。
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CpG-adjuvanted virus-like particle vaccine induces protective immunity against Leishmania donovani infection
Visceral leishmaniasis (VL) poses a significant public health challenge due to the lack of an approved human vaccine. We attempted to enhance the efficacy of virus-like particle vaccines expressing the Leishmania donovani promastigote surface antigen (LdPSA-VLP) by adjuvanting with CpG oligodeoxynucleotide (CpG-ODN). Here, adjuvanted vaccine-induced immune responses and their efficacies in mice challenged with mCherry-expressing L. donovani promastigotes were evaluated. Adjuvanted LdPSA-VLP vaccination significantly elevated parasite-specific IgG, IgG1, IgG2a, and IgG2b serum antibody levels. Additionally, vaccinated mice exhibited enhanced germinal center B cells and splenic T cell activities, compared to unimmunized mice. Importantly, adjuvanted LdPSA-VLPs reduced the levels of inflammatory cytokines IFN-γ and IL-6 in visceral organs, leading to decreased total parasite burden and protection against L. donovani challenge. Our findings indicate that CpG-ODN enhanced the protection conferred by LdPSA-VLPs, offering a promising step toward effective VL vaccine development.
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