DAF-shielded baculovirus-vectored vaccine enhances protection against malaria sporozoite challenge in mice.

DAF-shielded baculovirus-vectored vaccine enhances protection against malaria sporozoite challenge in mice.
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DOI:
10.1186/s12936-017-2039-x
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发表时间:
2017-09-29
期刊:
影响因子:
3
通讯作者:
Yoshida S
Yoshida S
中科院分区:
医学3区
文献类型:
--
作者:
Iyori M;Yamamoto DS;Sakaguchi M;Mizutani M;Ogata S;Nishiura H;Tamura T;Matsuoka H;Yoshida S

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已有研究表明,基于“杆状病毒双表达系统(BDES)”的杆状病毒载体疫苗是一种有效的疟疾疫苗递送平台。然而,在体内使用这种疫苗平台的一个弱点是血清补体对病毒的灭活。为了实现补体耐药性,将编码人类衰变加速因子(hDAF)的基因纳入表达恶性疟原虫环孢子子蛋白(PfCSP)的BDES疟疾疫苗中。新开发的BDES疫苗,命名为BDES- spfcsp2 - spider,在病毒包膜表面有效地显示hDAF和PfCSP,在体外和体内均产生补体耐药。重要的是,在小鼠肌肉注射后,BDES-sPfCSP2-Spider疫苗对表达PfCSP的转基因伯氏疟原虫孢子虫的攻击具有更高的保护效力(60%),比对照疫苗BDES-sPfCSP2-Spier(30%)更高。daf屏蔽的bdes疫苗作为对抗孢子虫挑战的新疟疾疫苗平台具有巨大的开发潜力。本文的在线版本(doi:10.1186/s12936-017-2039-x)包含补充材料,可供授权用户使用。
Previous studies have shown that the baculovirus-vectored vaccine based on the “baculovirus dual expression system (BDES)” is an effective vaccine delivery platform for malaria. However, a point of weakness remaining for use of this vaccine platform in vivo concerns viral inactivation by serum complement. In an effort to achieve complement resistance, the gene encoding the human decay-accelerating factor (hDAF) was incorporated into the BDES malaria vaccine expressing the Plasmodium falciparum circumsporozoite protein (PfCSP). The newly-developed BDES vaccine, designated BDES-sPfCSP2-Spider, effectively displayed hDAF and PfCSP on the surface of the viral envelope, resulting in complement resistance both in vitro and in vivo. Importantly, upon intramuscular inoculation into mice, the BDES-sPfCSP2-Spider vaccine had a higher protective efficacy (60%) than that of the control vaccine BDES-sPfCSP2-Spier (30%) against challenge with transgenic Plasmodium berghei sporozoites expressing PfCSP. DAF-shielded BDES-vaccines offer great potential for development as a new malaria vaccine platform against the sporozoite challenge. The online version of this article (doi:10.1186/s12936-017-2039-x) contains supplementary material, which is available to authorized users.
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