Yoon Keon-Woong, Chu Ki Back, Eom Gi-Deok, Mao Jie, Moon Eun-Kyung, Kim Sung Soo, Quan Fu-Shi
Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul.
Department of Parasitology, Inje University College of Medicine.
J Infect Dis. 2025 Apr 15;231(4):998-1007. doi: 10.1093/infdis/jiae526.
Visceral leishmaniasis 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 (VLP) vaccines expressing the Leishmania donovani promastigote surface antigen (LdPSA) by adjuvanting with CpG oligodeoxynucleotide. Here, we evaluated adjuvanted vaccine-induced immune responses and their efficacies in mice challenged with mCherry-expressing L donovani promastigotes. Adjuvanted LdPSA-VLP vaccination significantly elevated parasite-specific IgG serum antibody levels. Additionally, vaccinated mice exhibited enhanced germinal center B cells and splenic T-cell activities as compared with unimmunized mice. Importantly, adjuvanted LdPSA-VLPs reduced the levels of inflammatory cytokines interferon γ and interleukin 6 in visceral organs, leading to decreased total parasite burden and protection against L donovani challenge. Our findings indicate that CpG oligodeoxynucleotide enhanced the protection conferred by LdPSA-VLPs, offering a promising step toward effective visceral leishmaniasis vaccine development.
由于缺乏获批的人类疫苗，内脏利什曼病构成了重大的公共卫生挑战。我们试图通过用CpG寡脱氧核苷酸作为佐剂来提高表达杜氏利什曼原虫前鞭毛体表面抗原（LdPSA）的病毒样颗粒（VLP）疫苗的效力。在此，我们评估了佐剂疫苗诱导的免疫反应及其在受到表达mCherry的杜氏利什曼原虫前鞭毛体攻击的小鼠中的效力。佐剂LdPSA-VLP疫苗接种显著提高了寄生虫特异性IgG血清抗体水平。此外，与未免疫的小鼠相比，接种疫苗的小鼠生发中心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性细胞因子干扰素γ和白细胞介素6的水平，导致总寄生虫负荷降低，并对杜氏利什曼原虫攻击产生保护作用。我们的研究结果表明，CpG寡脱氧核苷酸增强了LdPSA-VLPs提供的保护，为有效的内脏利什曼病疫苗开发迈出了有希望的一步。
