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基于修饰信使 RNA 的疫苗可引发强烈的免疫应答,并保护豚鼠免受埃博拉病毒病的侵害。

Modified mRNA-Based Vaccines Elicit Robust Immune Responses and Protect Guinea Pigs From Ebola Virus Disease.

机构信息

Department of Pathology, University of Texas Medical Branch, Galveston, Texas.

Moderna Therapeutics, Cambridge, Massachusetts.

出版信息

J Infect Dis. 2018 Jan 17;217(3):451-455. doi: 10.1093/infdis/jix592.

Abstract

Most current Ebola virus (EBOV) vaccine candidates are based on viral vectors, some of which cause side effects or require complex manufacturing. Modified mRNA vaccines are easily produced, safe, and are highly immunogenic. We developed 2 mRNA vaccines based on the EBOV envelope glycoprotein, which differed by the nature of signal peptide for improved glycoprotein post-translational translocation. The mRNAs were formulated with lipid nanoparticles to facilitate delivery. Vaccination of guinea pigs induced EBOV-specific IgG and neutralizing antibody responses and 100% survival after EBOV infection. The efficacy of our mRNA vaccine combined with preclinical safety data supports testing in clinical studies.

摘要

大多数当前的埃博拉病毒 (EBOV) 疫苗候选物都是基于病毒载体的,其中一些会引起副作用或需要复杂的制造工艺。修饰后的 mRNA 疫苗易于生产、安全且具有高度的免疫原性。我们基于埃博拉病毒包膜糖蛋白开发了 2 种 mRNA 疫苗,它们通过信号肽的性质不同来改善糖蛋白的翻译后易位。这些 mRNA 与脂质纳米颗粒一起配制以促进递呈。豚鼠接种疫苗后可诱导产生埃博拉病毒特异性 IgG 和中和抗体应答,并且在埃博拉病毒感染后 100%存活。我们的 mRNA 疫苗的功效和临床前安全性数据支持在临床试验中进行测试。

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