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本文引用的文献

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Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia.在利比里亚进行的两种预防埃博拉疫苗的2期安慰剂对照试验。
N Engl J Med. 2017 Oct 12;377(15):1438-1447. doi: 10.1056/NEJMoa1614067.
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Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses.针对H10N8和H7N9流感病毒的mRNA疫苗免疫原性的临床前和临床证明
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Administration of nucleoside-modified mRNA encoding broadly neutralizing antibody protects humanized mice from HIV-1 challenge.核苷修饰 mRNA 编码的广泛中和抗体的给药可保护人源化小鼠免受 HIV-1 挑战。
Nat Commun. 2017 Mar 2;8:14630. doi: 10.1038/ncomms14630.
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Modified mRNA Vaccines Protect against Zika Virus Infection.改良型信使核糖核酸疫苗可预防寨卡病毒感染。
Cell. 2017 Mar 9;168(6):1114-1125.e10. doi: 10.1016/j.cell.2017.02.017. Epub 2017 Feb 17.
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Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.单次低剂量核苷修饰的mRNA疫苗对寨卡病毒的防护作用
Nature. 2017 Mar 9;543(7644):248-251. doi: 10.1038/nature21428. Epub 2017 Feb 2.
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Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose.树枝状聚合物-RNA纳米颗粒单剂量给药可对致死性埃博拉病毒、H1N1流感病毒和刚地弓形虫感染产生保护性免疫。
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An mRNA Vaccine Encoding Rabies Virus Glycoprotein Induces Protection against Lethal Infection in Mice and Correlates of Protection in Adult and Newborn Pigs.一种编码狂犬病病毒糖蛋白的mRNA疫苗可诱导小鼠抵抗致死性感染，并与成年和新生猪的保护相关指标相关。
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The effect of dose on the safety and immunogenicity of the VSV Ebola candidate vaccine: a randomised double-blind, placebo-controlled phase 1/2 trial.剂量对VSV埃博拉候选疫苗安全性和免疫原性的影响：一项随机双盲、安慰剂对照的1/2期试验。
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Aerosolized Ebola vaccine protects primates and elicits lung-resident T cell responses.雾化埃博拉疫苗可保护灵长类动物并引发肺驻留T细胞反应。
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mRNA-based therapeutics--developing a new class of drugs.mRNA 疗法——开发一类新药。
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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.

DOI:10.1093/infdis/jix592
PMID:29281112
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5853918/
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。