A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection.
A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection.
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DOI：
10.1038/s41467-023-41376-6
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发表时间：
2023-09-12
影响因子：
16.6
通讯作者：
Bukreyev, Alexander
中科院分区：
文献类型：
--
作者：
Ronk, Adam J.;Lloyd, Nicole M.;Zhang, Min;Atyeo, Caroline;Perrett, Hailee R.;Mire, Chad E.;Hastie, Kathryn M.;Sanders, Rogier W.;Brouwer, Philip J. M.;Saphire, Erica Olmann;Ward, Andrew B.;Ksiazek, Thomas G.;Alvarez Moreno, Juan Carlos;Thaker, Harshwardhan M.;Alter, Galit;Himansu, Sunny;Carfi, Andrea;Bukreyev, Alexander
拉沙病毒是沙粒病毒科的一员，它可导致人类感染，症状从无症状到严重出血性疾病不等，病死率较高。我们设计并制备了脂质纳米颗粒包裹的修饰信使核糖核酸（mRNA）疫苗，其编码野生型拉沙病毒约西亚毒株糖蛋白复合物或拉沙病毒糖蛋白复合物的预融合稳定构象。哈特利豚鼠分别用两种构建体以10微克的剂量接种，间隔28天。接种诱导了针对糖蛋白复合物预融合构象的强结合抗体反应，在预融合稳定糖蛋白复合物构建体组中这种反应明显更强，并显示出强大的Fc介导效应。然而，仅在部分而非所有动物中检测到拉沙病毒中和抗体活性。在用致死剂量的拉沙病毒攻击后，所有接种的动物都免于死亡和严重疾病。尽管确切的保护机制仍不清楚，且本研究未对细胞介导的免疫反应进行评估，但这些数据表明mRNA作为针对拉沙病毒的疫苗平台具有前景，并且在没有病毒中和抗体的情况下也可实现对拉沙病毒的保护。
人类感染拉沙病毒可导致严重疾病，包括出血热。在此，作者描述了一种基于mRNA的拉沙病毒疫苗，该疫苗在豚鼠感染模型中显示出在不需要中和抗体的情况下具有保护作用。
Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies. Lassa virus infections in humans can result in severe disease, including hemorrhagic fever. Here the authors describe an mRNA-based Lassa virus vaccine that shows protection without requirement for neutralizing antibody in a guinea pig model of infection.
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DOI：
10.1093/infdis/jiy123
发表时间：
2018-05-25
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Kainulainen MH;Spengler JR;Welch SR;Coleman-McCray JD;Harmon JR;Klena JD;Nichol ST;Albariño CG;Spiropoulou CF
通讯作者：
Spiropoulou CF
影响因子：
11.8
作者：
Amorosa, Valerianna;MacNeil, Adam;Nichol, Stuart T.
通讯作者：
Nichol, Stuart T.
影响因子：
5.4
作者：
Carnec, Xavier;Mateo, Mathieu;Baize, Sylvain
通讯作者：
Baize, Sylvain
影响因子：
2.4
作者：
Bell, T. M.;Shaia, C. I.;Cashman, K. A.
通讯作者：
Cashman, K. A.
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group