Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites
Baculovirus-Vectored Multistage Plasmodium vivax Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites
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DOI：
10.1128/iai.02040-14
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发表时间：
2014-10-01
影响因子：
3.1
通讯作者：
Yoshida, Shigeto
中科院分区：
文献类型：
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作者：
Mizutani, Masanori;Iyori, Mitsuhiro;Yoshida, Shigeto
针对疟原虫红细胞前期和性阶段的多阶段疟疾疫苗可以有效地保护个体免受蚊子叮咬的感染，并分别提供针对寄生虫性阶段的传播阻断（TB）活性。这一策略可以帮助预防个人感染疟疾，并在更大范围内预防疟疾在流行社区的传播。在这里，我们描述了一种多阶段间日疟原虫疫苗的开发，该疫苗同时表达该物种的间日疟原虫环子孢子蛋白（PvCSP）和P25（Pvs 25）蛋白作为融合蛋白，从而分别用作红细胞前疫苗和TB疫苗。评价了一种基于杆状病毒双表达系统（BDES）的新概念疫苗平台。BDES-Pvs 25-PvCSP疫苗在病毒包膜上显示Pvs 25-PvCSP融合蛋白的正确折叠，并且在体外转导哺乳动物细胞后高度表达。该疫苗诱导了高水平的抗Pvs 25和PvCSP抗体，并在小鼠中引发了针对表达相应间日疟原虫抗原的转基因伯氏疟原虫寄生虫的保护（43%）和TB（82%）效力。我们的数据表明，我们的BDES，作为亚单位和DNA疫苗的功能，可以提供一个有前途的多阶段疫苗，能够通过一个单一的免疫方案提供一个有效的抗疟疾红细胞前和结核病的反应。
A multistage malaria vaccine targeting the pre-erythrocytic and sexual stages of Plasmodium could effectively protect individuals against infection from mosquito bites and provide transmission-blocking (TB) activity against the sexual stages of the parasite, respectively. This strategy could help prevent malaria infections in individuals and, on a larger scale, prevent malaria transmission in communities of endemicity. Here, we describe the development of a multistage Plasmodium vivax vaccine which simultaneously expresses P. vivax circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic vaccine and a TB vaccine, respectively. A new-concept vaccine platform based on the baculovirus dual-expression system (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP and elicited protective (43%) and TB (82%) efficacies against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice. Our data indicate that our BDES, which functions as both a subunit and DNA vaccine, can offer a promising multistage vaccine capable of delivering a potent antimalarial pre-erythrocytic and TB response via a single immunization regimen.