A Single-Dose Live-Attenuated Zika Virus Vaccine with Controlled Infection Rounds that Protects against Vertical Transmission.

A Single-Dose Live-Attenuated Zika Virus Vaccine with Controlled Infection Rounds that Protects against Vertical Transmission.
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DOI:
10.1016/j.chom.2018.09.008
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发表时间:
2018-10-10
影响因子:
30.3
通讯作者:
Shi PY
Shi PY
中科院分区:
医学1区
文献类型:
--
作者:
Xie X;Kum DB;Xia H;Luo H;Shan C;Zou J;Muruato AE;Medeiros DBA;Nunes BTD;Dallmeier K;Rossi SL;Weaver SC;Neyts J;Wang T;Vasconcelos PFC;Shi PY

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寨卡病毒(ZIKV)是寨卡病毒病的一种常见病原体。迫切需要用于孕妇的具有最佳安全性和免疫原性的ZIKV疫苗。为了实现这一目标,我们已经开发出一种单剂量减毒活疫苗候选物,该候选物以受控的、有限的感染轮次感染细胞。该疫苗在病毒衣壳蛋白中含有9个氨基酸缺失,并且在表达全长衣壳蛋白的细胞中复制至>106焦点形成单位(FFU)/ml的滴度。用一个剂量(IO 5 FFU)免疫A129小鼠不产生病毒血症,但在用流行性ZIKV毒株(IO 6PFU)攻击后引起完全防止病毒血症、发病率和死亡率的保护性免疫。单剂量疫苗接种也完全预防了孕鼠感染和母婴传播。将疫苗(104 FFU)颅内注射给1日龄小鼠,未引起任何疾病或死亡,强调了该候选疫苗的安全性。用于孕妇的ZIKV疫苗需要安全性和免疫原性之间的最佳平衡。Xie等人开发了一种减毒活疫苗候选物,可以通过受控的有限感染轮次感染细胞。疫苗的单次剂量免疫可预防妊娠小鼠中ZIKV的垂直传播。
Zika virus (ZIKV) infection of the mother during pregnancy causes devastating Zika congenital syndrome in the offspring. A ZIKV vaccine with optimal safety and immunogenicity for use in pregnant women is critically needed. Towards this goal, we have developed a singledose live-attenuated vaccine candidate that infects cells with controlled, limited infection rounds. The vaccine contains a 9-amino acid deletion in the viral capsid protein, and replicates to titers of >106 focus-forming units (FFU)/ml in cells expressing the full-length capsid protein. Immunization of A129 mice with one dose (105 FFU) did not produce viremia, but elicited protective immunity that completely prevented viremia, morbidity, and mortality after challenge with an epidemic ZIKV strain (106 PFU). A single-dose vaccination also fully prevented infection of pregnant mice and maternal-to-fetal transmission. Intracranial injection of the vaccine (104 FFU) to one-day-old mice did not cause any disease or death, underscoring the safety of this vaccine candidate. A ZIKV vaccine for use in pregnant women requires an optimal balance between safety and immunogenicity. Xie et al. developed a live-attenuated vaccine candidate that can infect cells with controlled, limited infection rounds. A single-dose immunization of the vaccine prevents vertical transmission of ZIKV in pregnant mice.
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影响因子: 17.1
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