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载有 DAF 蛋白的杆状病毒载体疫苗增强了对小鼠疟原虫感染的保护作用。

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

机构信息

Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, First Natural Science Building 1A219, Kakuma-machi, Kanazawa, 920-1192, Japan.

Division of Medical Zoology, Department of Infection and Immunity, Jichi Medical University, Shimotsuke, Tochigi, Japan.

出版信息

Malar J. 2017 Sep 29;16(1):390. doi: 10.1186/s12936-017-2039-x.

Abstract

BACKGROUND

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).

RESULTS

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.

CONCLUSION

DAF-shielded BDES-vaccines offer great potential for development as a new malaria vaccine platform against the sporozoite challenge.

摘要

背景

先前的研究表明,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传递平台。然而,该疫苗平台在体内应用的一个弱点仍然是病毒被血清补体灭活。为了实现补体抗性,编码人衰变加速因子(hDAF)的基因被整合到表达恶性疟原虫环子孢子蛋白(PfCSP)的 BDES 疟疾疫苗中。

结果

新开发的 BDES 疫苗,命名为 BDES-sPfCSP2-Spider,有效地在病毒包膜表面展示 hDAF 和 PfCSP,从而在体外和体内均表现出补体抗性。重要的是,在肌肉内接种小鼠后,BDES-sPfCSP2-Spider 疫苗对表达 PfCSP 的转基因伯氏疟原虫孢子虫的挑战具有比对照疫苗 BDES-sPfCSP2-Spier(30%)更高的保护效力(60%)。

结论

DAF 屏蔽的 BDES 疫苗具有作为针对孢子虫挑战的新型疟疾疫苗平台的巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a943/5622557/1e315134e259/12936_2017_2039_Fig1_HTML.jpg

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