PDF(Pubmed)
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。尽管疫苗最近已经上市，它们的功效并不理想。我们产生了表达伯氏疟原虫顶膜抗原1（AMA1）或微丝相关抗原（MIC）的病毒样颗粒（VLP），并比较了它们在BALB/c小鼠中的功效。我们发现，从AMA1VLP或MICVLP免疫小鼠获得的免疫血清与所选择的抗原和整个伯氏疟原虫裂解物抗原特异性相互作用，表明抗体具有高度的寄生虫特异性。与对照组相比，两种VLP疫苗均显着提高了小鼠腹股沟淋巴结中生发中心B细胞的频率。但是，只有接受MICVLP的小鼠在伯氏疟原虫攻击感染后，血液中的CD4+T细胞反应显着增强。AMA1和MICVLP显着抑制TNF-α和白介素-10的产生，但对干扰素-γ的影响可忽略不计。两种VLP均可预防免疫小鼠中寄生虫的过度积累，尽管MICVLP诱导的寄生虫负荷降低比AMA1诱导的更有效。两种VLP在预防体重减轻方面同样有效。我们的发现表明，MICVLP是针对小鼠实验性疟疾的有效诱导剂，应成为进一步开发的重点。
