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含利什曼原虫表面糖蛋白 GP63 的病毒样颗粒诱导的疫苗效力。

Vaccine efficacy induced by virus-like particles containing Leishmania donovani surface glycoprotein GP63.

机构信息

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea.

Department of Parasitology, Inje University College of Medicine, Busan, Republic of Korea.

出版信息

PLoS Negl Trop Dis. 2024 Jun 10;18(6):e0012229. doi: 10.1371/journal.pntd.0012229. eCollection 2024 Jun.

DOI:10.1371/journal.pntd.0012229
PMID:38857253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11164348/
Abstract

Leishmania donovani surface glycoprotein 63 (GP63) is a major virulence factor involved in parasite escape and immune evasion. In this study, we generated virus-like particles (VLPs) expressing L. donovani GP63 using the baculovirus expression system. Mice were intramuscularly immunized with GP63-VLPs and challenged with L. donovani promastigotes. GP63-VLP immunization elicited higher levels of L. donovani antigen-specific serum antibodies and enhanced splenic B cell, germinal center B cell, CD4+, and CD8+ T cell responses compared to unimmunized controls. GP63-VLPs inhibited the influx of pro-inflammatory cytokines IFN-γ and IL-6 in the livers, as well as thwarting the development of splenomegaly in immunized mice. Upon L. donovani challenge infection, a drastic reduction in splenic parasite burden was observed in VLP-immunized mice. These results indicate that GP63-VLPs immunization conferred protection against L. donovani challenge infection by inducing humoral and cellular immunity in mice.

摘要

利什曼原虫表面糖蛋白 63（GP63）是一种主要的毒力因子，参与寄生虫逃避和免疫逃逸。在这项研究中，我们使用杆状病毒表达系统生成了表达 L. donovani GP63 的病毒样颗粒（VLPs）。用 GP63-VLPs 对小鼠进行肌肉内免疫，并以 L. donovani 前鞭毛体进行攻毒。与未免疫对照组相比，GP63-VLP 免疫可诱导更高水平的 L. donovani 抗原特异性血清抗体，并增强脾脏 B 细胞、生发中心 B 细胞、CD4+和 CD8+T 细胞反应。GP63-VLPs 抑制了肝脏中促炎细胞因子 IFN-γ和 IL-6 的流入，并阻止了免疫小鼠的脾肿大发展。在 L. donovani 攻毒感染后，在 VLP 免疫的小鼠中观察到脾脏寄生虫负荷的急剧减少。这些结果表明，GP63-VLPs 免疫通过在小鼠中诱导体液和细胞免疫来赋予对抗 L. donovani 攻毒感染的保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/dd821b044b0d/pntd.0012229.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/b58682e0e326/pntd.0012229.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/30d3116c8052/pntd.0012229.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/253a4f6a647f/pntd.0012229.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/f042e4979908/pntd.0012229.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/e1467bc8a968/pntd.0012229.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/6a418d467cec/pntd.0012229.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/cf18ab3dc9f9/pntd.0012229.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/dd821b044b0d/pntd.0012229.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/b58682e0e326/pntd.0012229.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/30d3116c8052/pntd.0012229.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/253a4f6a647f/pntd.0012229.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/f042e4979908/pntd.0012229.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/e1467bc8a968/pntd.0012229.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/6a418d467cec/pntd.0012229.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/cf18ab3dc9f9/pntd.0012229.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/273c/11164348/dd821b044b0d/pntd.0012229.g008.jpg

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