Passive Transfer of Immune Sera Induced by a Zika Virus-Like Particle Vaccine Protects AG129 Mice Against Lethal Zika Virus Challenge.
Passive Transfer of Immune Sera Induced by a Zika Virus-Like Particle Vaccine Protects AG129 Mice Against Lethal Zika Virus Challenge.
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DOI：
10.1016/j.ebiom.2017.12.010
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发表时间：
2018-01
期刊：
影响因子：
11.1
通讯作者：
Alexander J
中科院分区：
文献类型：
--
作者：
Espinosa D;Mendy J;Manayani D;Vang L;Wang C;Richard T;Guenther B;Aruri J;Avanzini J;Garduno F;Farness P;Gurwith M;Smith J;Harris E;Alexander J
寨卡病毒（ZIKV）由于与发育中胎儿的出生缺陷和成人的格林-巴利综合症有关，对公共健康构成严重威胁。我们正在开发一种基于瞬时转染 HEK293 细胞中产生的病毒样颗粒 (VLP) 的 ZIKV 疫苗。该基因构建体由位于异源信号序列下游的 ZIKV prM 和包膜结构蛋白基因组成。为了更好地了解 VLP 疫苗诱导的体液反应和保护相关性 (CoP)，我们在免疫活性小鼠 (C57Bl/6 x Balb/c) 中评估了有或没有明矾的 VLP 免疫原性，并观察到中和抗体的有效诱导以及明矾的剂量节省效应。为了评估免疫血清的功效，我们在 AG129 小鼠中进行了被动转移实验。根据血液中的病毒 RNA 水平测量，在 ZIKV 感染之前接受免疫血清的小鼠表现出病毒复制显着减少，并且保持健康，而对照小鼠则死于感染。结果强调了这种 ZIKV VLP 候选疫苗引起的抗体反应的保护作用。这些研究将有助于确定最佳疫苗配方，有助于临床开发疫苗的转化工作，并协助定义免疫学 CoP。由结构蛋白 prME 组成的寨卡病毒 VLP 在 C57Bl/6 x Balb/c 小鼠中诱导高滴度中和抗体。寨卡病毒 VLP 疫苗诱导的抗体被动转移到 AG129 小鼠体内，可防止致命的寨卡病毒攻击。循环中和抗体的水平与抵御寨卡病毒攻击的能力相关。寨卡病毒通过蚊子传播给人类，由于与发育中的胎儿出生缺陷和成人神经系统疾病有关，因此对健康构成严重威胁。我们试图开发一种基于病毒样颗粒 (VLP) 的寨卡疫苗，这种颗粒在结构上与母体病毒相同，但不包含遗传物质。当给小鼠注射寨卡病毒样颗粒疫苗时，会诱导产生抗体。当这些抗体转移到易受寨卡病毒感染的小鼠体内时，可以保护动物免受寨卡病毒的攻击和死亡。我们的结果将支持 Zika VLP 疫苗的持续开发和人体测试。
Zika virus (ZIKV) poses a serious public health threat due to its association with birth defects in developing fetuses and Guillain-Barré Syndrome in adults. We are developing a ZIKV vaccine based on virus-like particles (VLPs) generated in transiently transfected HEK293 cells. The genetic construct consists of the prM and envelope structural protein genes of ZIKV placed downstream from a heterologous signal sequence. To better understand the humoral responses and correlates of protection (CoP) induced by the VLP vaccine, we evaluated VLP immunogenicity with and without alum in immune-competent mice (C57Bl/6 x Balb/c) and observed efficient induction of neutralizing antibody as well as a dose-sparing effect of alum. To assess the efficacy of the immune sera, we performed passive transfer experiments in AG129 mice. Mice that received the immune sera prior to ZIKV infection demonstrated significantly reduced viral replication as measured by viral RNA levels in the blood and remained healthy, whereas control mice succumbed to infection. The results underscore the protective effect of the antibody responses elicited by this ZIKV VLP vaccine candidate. These studies will help define optimal vaccine formulations, contribute to translational efforts in developing a vaccine for clinical development, and assist in the definition of immunologic CoP. Zika virus VLP comprised of structural proteins prME induces high-titer neutralizing antibodies in C57Bl/6 x Balb/c mice. Zika virus VLP vaccine-induced antibodies passively transferred to AG129 mice protects against lethal Zika virus challenge. Level of circulating neutralizing antibody is correlated with protection against Zika virus challenge. Zika virus, transmitted by mosquito to humans, poses a serious health threat due to its association with birth defects in developing fetuses and neurological disorders in adults. We sought to develop a Zika vaccine based on virus-like particles (VLPs), which are structurally the same as the parent virus but don't contain genetic material. The Zika VLP vaccine, when administered to mice, induced antibodies. These antibodies, when transferred to a mouse susceptible to Zika virus infection, protected the animals against Zika virus challenge and death. Our results will support continued development of the Zika VLP vaccine and testing in human subjects.
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影响因子：
11.8
作者：
Foy BD;Kobylinski KC;Chilson Foy JL;Blitvich BJ;Travassos da Rosa A;Haddow AD;Lanciotti RS;Tesh RB
通讯作者：
Tesh RB
影响因子：
3.8
作者：
Faye O;Freire CC;Iamarino A;Faye O;de Oliveira JV;Diallo M;Zanotto PM;Sall AA
通讯作者：
Sall AA
影响因子：
16.6
作者：
Hasan SS;Miller A;Sapparapu G;Fernandez E;Klose T;Long F;Fokine A;Porta JC;Jiang W;Diamond MS;Crowe JE Jr;Kuhn RJ;Rossmann MG
通讯作者：
Rossmann MG
影响因子：
1.9
作者：
Ansar, Vibhuti;Valadi, Nojan
通讯作者：
Valadi, Nojan
影响因子：
158.5
作者：
Driggers, R. W.;Ho, C. -Y.;Vapalahti, O.
通讯作者：
Vapalahti, O.