Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice.
Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice.
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DOI：
10.1038/s41541-021-00345-0
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发表时间：
2021-06-18
期刊：
影响因子：
9.2
通讯作者：
Angov E
中科院分区：
文献类型：
--
作者：
Mallory KL;Taylor JA;Zou X;Waghela IN;Schneider CG;Sibilo MQ;Punde NM;Perazzo LC;Savransky T;Sedegah M;Dutta S;Janse CJ;Pardi N;Lin PJC;Tam YK;Weissman D;Angov E
人类疟疾影响着世界上绝大多数人口，其中恶性疟原虫物种造成最高的发病率和死亡率。由于没有获得许可的疫苗和领先的候选人在该领域实现次优保护，对有效免疫预防选择的需求继续激励疟疾研究界探索替代技术。mRNA学科的最新进展将长期被忽视的平台提升到了传染病研究的最前沿。作为疟疾寄生虫侵入阶段的免疫显性外壳蛋白，环子孢子蛋白（PfCSP）被选为评估mRNA疟疾疫苗的免疫原性和保护潜力的抗原。在哺乳动物细胞转染实验中，PfCSP mRNA表达良好，并与细胞结合。在向体内鼠模型的过渡中，应用脂质纳米颗粒（LNP）包封以保护mRNA并将其递送至细胞翻译机器并提供佐剂活性。探索了一系列因素的免疫原性效应，如制剂、剂量、数量和免疫间隔。PfCSP mRNA-LNP实现了针对两种伯氏疟原虫PfCSP转基因寄生虫株感染的无菌保护，其中mRNA剂量和接种间隔对结果具有更大的影响。本研究作为红细胞前疟疾的评估，PfCSP mRNA疫苗候选物导致无菌保护，具有影响保护效力的许多因素，使其成为进一步研究的令人信服的候选物。
Human malaria affects the vast majority of the world’s population with the Plasmodium falciparum species causing the highest rates of morbidity and mortality. With no licensed vaccine and leading candidates achieving suboptimal protection in the field, the need for an effective immunoprophylactic option continues to motivate the malaria research community to explore alternative technologies. Recent advances in the mRNA discipline have elevated the long-neglected platform to the forefront of infectious disease research. As the immunodominant coat protein of the invasive stage of the malaria parasite, circumsporozoite protein (PfCSP) was selected as the antigen of choice to assess the immunogenic and protective potential of an mRNA malaria vaccine. In mammalian cell transfection experiments, PfCSP mRNA was well expressed and cell associated. In the transition to an in vivo murine model, lipid nanoparticle (LNP) encapsulation was applied to protect and deliver the mRNA to the cell translation machinery and supply adjuvant activity. The immunogenic effect of an array of factors was explored, such as formulation, dose, number, and interval of immunizations. PfCSP mRNA-LNP achieved sterile protection against infection with two P. berghei PfCSP transgenic parasite strains, with mRNA dose and vaccination interval having a greater effect on outcome. This investigation serves as the assessment of pre-erythrocytic malaria, PfCSP mRNA vaccine candidate resulting in sterile protection, with numerous factors affecting protective efficacy, making it a compelling candidate for further investigation.
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DOI：
10.1126/science.aad8711
发表时间：
2016-06-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert WV;Bell TA;Schaening C
通讯作者：
Schaening C
DOI：
10.1084/jem.168.6.2373
发表时间：
1988-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coutelier JP;van der Logt JT;Heessen FW;Vink A;van Snick J
通讯作者：
van Snick J
影响因子：
7.8
作者：
Buschmann MD;Carrasco MJ;Alishetty S;Paige M;Alameh MG;Weissman D
通讯作者：
Weissman D
影响因子：
3.1
作者：
Ferraro, B.;Talbott, K. T.;Weiner, D. B.
通讯作者：
Weiner, D. B.
DOI：
10.1007/978-1-61737-967-3_1
发表时间：
2011-01-01
期刊：
HETEROLOGOUS GENE EXPRESSION IN E COLI: METHODS AND PROTOCOLS
影响因子：
--
作者：
Angov, Evelina;Legler, Patricia M.;Mease, Ryan M.
通讯作者：
Mease, Ryan M.