A recombinant VSV-vectored vaccine rapidly protects nonhuman primates against lethal Nipah virus disease.
A recombinant VSV-vectored vaccine rapidly protects nonhuman primates against lethal Nipah virus disease.
复制标题
DOI：
10.1073/pnas.2200065119
复制
发表时间：
2022-03-22
影响因子：
11.1
通讯作者：
Geisbert TW
中科院分区：
文献类型：
--
作者：
Foster SL;Woolsey C;Borisevich V;Agans KN;Prasad AN;Deer DJ;Geisbert JB;Dobias NS;Fenton KA;Cross RW;Geisbert TW
人们越来越担心尼帕病毒（NiV）的大流行潜力。与 SARS-CoV-2 类似，NiV 是一种通过呼吸道飞沫传播的 RNA 病毒。目前还没有获得人类使用许可的 NiV 疫苗。虽然一些预防性疫苗在保护动物免受致命性 NiV 疾病方面显示出了希望，但大多数研究都是在接种疫苗后 1 个月内评估保护作用。然而，为了遏制和控制疫情，需要能够在几天而不是几个月内迅速提供保护的疫苗。在这里，我们表明表达 NiV 糖蛋白的重组水泡性口炎病毒载体可以完全保护在 NiV 暴露前 7 天接种疫苗的猴子，以及 67% 在 NiV 攻击前 3 天接种疫苗的动物。尼帕病毒 (NiV) 是一种新兴的高致命性人畜共患疾病，与 SARS-CoV-2 一样，可以通过呼吸道飞沫传播。需要快速控制 NiV 爆发的单次注射疫苗。为了评估疫苗诱导快速保护的能力，我们用表达 NiV 孟加拉国株糖蛋白 (NiVBG) (rVSV-ΔG-NiVBG) 的重组水泡性口炎病毒 (VSV) 免疫非洲绿猴。 3 或 7 天后，用致死剂量的 NiVB 攻击猴子。所有在 NiVB 暴露前 7 天接种 rVSV-ΔG-NiVBG 疫苗的猴子都免受致命疾病的影响，而 67% 在 NiVB 攻击前 3 天接种疫苗的动物存活下来。疫苗保护与自然杀伤细胞和细胞毒性 T 细胞转录特征相关，而致死性与持续的干扰素信号传导相关。接种疫苗的幸存者中的 NiV G 特异性抗体证实了其他转录组学发现，支持体液免疫的激活。这项研究表明，基于 rVSV 的疫苗可能有助于快速保护人类免受 NiV 感染。
Concern has increased about the pandemic potential of Nipah virus (NiV). Similar to SARS-CoV-2, NiV is an RNA virus that is transmitted by respiratory droplets. There are currently no NiV vaccines licensed for human use. While several preventive vaccines have shown promise in protecting animals against lethal NiV disease, most studies have assessed protection 1 mo after vaccination. However, in order to contain and control outbreaks, vaccines that can rapidly confer protection in days rather than months are needed. Here, we show that a recombinant vesicular stomatitis virus vector expressing the NiV glycoprotein can completely protect monkeys vaccinated 7 d prior to NiV exposure and 67% of animals vaccinated 3 d before NiV challenge. Nipah virus (NiV) is an emerging highly lethal zoonotic disease that, like SARS-CoV-2, can be transmitted via respiratory droplets. Single-injection vaccines that rapidly control NiV outbreaks are needed. To assess the ability of a vaccine to induce fast-acting protection, we immunized African green monkeys with a recombinant vesicular stomatitis virus (VSV) expressing the Bangladesh strain glycoprotein (NiVBG) of NiV (rVSV-ΔG-NiVBG). Monkeys were challenged 3 or 7 d later with a lethal dose of NiVB. All monkeys vaccinated with rVSV-ΔG-NiVBG 7 d prior to NiVB exposure were protected from lethal disease, while 67% of animals vaccinated 3 d before NiVB challenge survived. Vaccine protection correlated with natural killer cell and cytotoxic T cell transcriptional signatures, whereas lethality was linked to sustained interferon signaling. NiV G-specific antibodies in vaccinated survivors corroborated additional transcriptomic findings, supporting activation of humoral immunity. This study demonstrates that rVSV-based vaccines may have utility in rapidly protecting humans against NiV infection.
登录
查看更多内容
影响因子：
3.8
作者：
Hammoud DA;Lentz MR;Lara A;Bohannon JK;Feuerstein I;Huzella L;Jahrling PB;Lackemeyer M;Laux J;Rojas O;Sayre P;Solomon J;Cong Y;Munster V;Holbrook MR
通讯作者：
Holbrook MR
影响因子：
5.6
作者：
Freitas CMT;Johnson DK;Weber KS
通讯作者：
Weber KS
影响因子：
8
作者：
Huffman, Austin P.;Lin, Jeffrey H.;Vonderheide, Robert H.
通讯作者：
Vonderheide, Robert H.
影响因子：
3.7
作者：
Geisbert, Thomas W.;Daddario-DiCaprio, Kathleen M.;Broder, Christopher C.
通讯作者：
Broder, Christopher C.
影响因子：
8.8
作者：
Hidalgo, L. G.;Einecke, G.;Halloran, P. F.
通讯作者：
Halloran, P. F.