Vesicular stomatitis virus-based vaccine targeting plasmodium blood-stage antigens elicits immune response and protects against malaria with protein booster strategy.
Vesicular stomatitis virus-based vaccine targeting plasmodium blood-stage antigens elicits immune response and protects against malaria with protein booster strategy.
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DOI：
10.3389/fmicb.2022.1042414
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发表时间：
2022
影响因子：
5.2
通讯作者：
Cheng, Yang
中科院分区：
文献类型：
--
作者：
Sun, Yifan;Shi, Xiaodan;Lu, Feng;Fu, Haitian;Yin, Yi;Xu, Jiahui;Jin, Cheng;Han, Eun-taek;Huang, Xuan;Chen, Yongquan;Dong, Chunsheng;Cheng, Yang
裂殖子侵入人体红细胞是疟疾发病机制中的关键步骤。裂殖子入侵相关蛋白可能成为疟疾疫苗开发的潜在靶点。目前正在对研制的新型病毒载体疟疾疫苗方案进行临床试验。水泡性口炎病毒（VSV）是一种单链负链RNA病毒，广泛用作病毒或癌症疫苗的载体。基于VSV的疟疾疫苗是否比基于参与寄生虫入侵的蛋白质的传统疫苗更有效，目前还不清楚。在这项研究中，我们使用反向遗传学系统构建重组VSV（rVSV）表达顶端膜蛋白1（AMA1），棒状体颈蛋白2（RON 2），和网织红细胞结合蛋白同源物5（RH5），这是恶性疟原虫入侵所需的。我们的研究结果表明，VSV为基础的病毒疫苗显着提高疟原虫特异性IgG水平和淋巴细胞增殖。VSV-PyAMA1和VSV-PyRON2sp初免-加强免疫方案可显著提高CD4+和CD8 + T细胞产生IL-2和IFN-γ的水平，并抑制体外侵袭。与同源rVSV初免-加强相比，rVSV初免-蛋白加强方案显著增加小鼠血清中的疟原虫抗原特异性IgG水平。此外，与传统抗原免疫相比，rVSV初免蛋白加强免疫在用约氏疟原虫17 XL攻击的小鼠中的保护效力更好。总之，我们的研究结果表明，VSV载体是疟疾疫苗开发和预防寄生虫病的新策略。
Merozoite invasion of the erythrocytes in humans is a key step in the pathogenesis of malaria. The proteins involved in the merozoite invasion could be potential targets for the development of malaria vaccines. Novel viral-vector-based malaria vaccine regimens developed are currently under clinical trials. Vesicular stomatitis virus (VSV) is a single-stranded negative-strand RNA virus widely used as a vector for virus or cancer vaccines. Whether the VSV-based malarial vaccine is more effective than conventional vaccines based on proteins involved in parasitic invasion is still unclear. In this study, we have used the reverse genetics system to construct recombinant VSVs (rVSVs) expressing apical membrane protein 1 (AMA1), rhoptry neck protein 2 (RON2), and reticulocyte-binding protein homolog 5 (RH5), which are required for Plasmodium falciparum invasion. Our results showed that VSV-based viral vaccines significantly increased Plasmodium-specific IgG levels and lymphocyte proliferation. Also, VSV-PyAMA1 and VSV-PyRON2sp prime-boost regimens could significantly increase the levels of IL-2 and IFN-γ-producing by CD4+ and CD8+ T cells and suppress invasion in vitro. The rVSV prime-protein boost regimen significantly increase Plasmodium antigen-specific IgG levels in the serum of mice compared to the homologous rVSV prime-boost. Furthermore, the protective efficacy of rVSV prime protein boost immunization in the mice challenged with P. yoelii 17XL was better compared to traditional antigen immunization. Together, our results show that VSV vector is a novel strategy for malarial vaccine development and preventing the parasitic diseases.
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评估表达外孢子虫蛋白和ME捕获的CHAD63-MVA矢量疫苗对疟疾个体中受控的人类疟疾感染的疗效。
DOI：
10.1093/infdis/jiu579
发表时间：
2015-04-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Hodgson SH;Ewer KJ;Bliss CM;Edwards NJ;Rampling T;Anagnostou NA;de Barra E;Havelock T;Bowyer G;Poulton ID;de Cassan S;Longley R;Illingworth JJ;Douglas AD;Mange PB;Collins KA;Roberts R;Gerry S;Berrie E;Moyle S;Colloca S;Cortese R;Sinden RE;Gilbert SC;Bejon P;Lawrie AM;Nicosia A;Faust SN;Hill AV
通讯作者：
Hill AV
影响因子：
6.4
作者：
Jones, Steven M.;Stroeher, Ute;Feldmann, Heinz
通讯作者：
Feldmann, Heinz
影响因子：
4
作者：
Boyle MJ;Reiling L;Osier FH;Fowkes FJ
通讯作者：
Fowkes FJ
影响因子：
3.1
作者：
Chawla, Bhavna;Mahajan, Babita;Kumar, Sanjai
通讯作者：
Kumar, Sanjai
影响因子：
6.7
作者：
Hojo-Souza, Natalia Satchiko;de Azevedo, Patrick Orestes;Gazzinelli, Ricardo Tostes
通讯作者：
Gazzinelli, Ricardo Tostes