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表达伯氏疟原虫微线体相关抗原的病毒样颗粒比表达顶膜抗原 1 的病毒样颗粒具有更好的保护效果。

Virus-like particles expressing microneme-associated antigen of Plasmodium berghei confer better protection than those expressing apical membrane antigen 1.

机构信息

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Korea.

Department of Parasitology, Inje University College of Medicine, Busan 47392, Korea.

出版信息

Parasites Hosts Dis. 2024 May;62(2):193-204. doi: 10.3347/PHD.24017. Epub 2024 May 27.

Abstract

Malaria is a global disease affecting a large portion of the world's population. Although vaccines have recently become available, their efficacies are suboptimal. We generated virus-like particles (VLPs) that expressed either apical membrane antigen 1 (AMA1) or microneme-associated antigen (MIC) of Plasmodium berghei and compared their efficacy in BALB/c mice. We found that immune sera acquired from AMA1 VLP- or MIC VLP-immunized mice specifically interacted with the antigen of choice and the whole P. berghei lysate antigen, indicating that the antibodies were highly parasite-specific. Both VLP vaccines significantly enhanced germinal center B cell frequencies in the inguinal lymph nodes of mice compared with the control, but only the mice that received MIC VLPs showed significantly enhanced CD4+ T cell responses in the blood following P. berghei challenge infection. AMA1 and MIC VLPs significantly suppressed TNF-α and interleukin-10 production but had a negligible effect on interferon-γ. Both VLPs prevented excessive parasitemia buildup in immunized mice, although parasite burden reduction induced by MIC VLPs was slightly more effective than that induced by AMA1. Both VLPs were equally effective at preventing body weight loss. Our findings demonstrated that the MIC VLP was an effective inducer of protection against murine experimental malaria and should be the focus of further development.

摘要

疟疾是一种全球性疾病,影响着世界上很大一部分人口。尽管最近已经有了疫苗,但它们的效果并不理想。我们生成了表达疟原虫伯氏疟原虫顶膜抗原 1(AMA1)或微线相关抗原(MIC)的病毒样颗粒(VLPs),并比较了它们在 BALB/c 小鼠中的功效。我们发现,从 AMA1 VLP 或 MIC VLP 免疫的小鼠获得的免疫血清特异性地与所选抗原和整个伯氏疟原虫裂解物抗原相互作用,表明抗体具有高度的寄生虫特异性。与对照组相比,两种 VLP 疫苗都显著增加了腹股沟淋巴结中生发中心 B 细胞的频率,但只有接受 MIC VLP 的小鼠在感染伯氏疟原虫后,血液中的 CD4+T 细胞反应显著增强。AMA1 和 MIC VLPs 显著抑制 TNF-α 和白细胞介素-10 的产生,但对干扰素-γ几乎没有影响。两种 VLPs 都能防止免疫小鼠中疟原虫过度繁殖,尽管 MIC VLPs 诱导的寄生虫负荷减少比 AMA1 更有效。两种 VLPs 在防止体重减轻方面同样有效。我们的研究结果表明,MIC VLP 是一种有效诱导抗鼠实验性疟疾的保护剂,应成为进一步开发的重点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6587/11150920/ee09ad0d39ae/phd-24017f1.jpg

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