A vaccine inducing solely cytotoxic T lymphocytes fully prevents Zika virus infection and fetal damage.
A vaccine inducing solely cytotoxic T lymphocytes fully prevents Zika virus infection and fetal damage.
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DOI：
10.1016/j.celrep.2021.109107
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发表时间：
2021-05-11
期刊：
影响因子：
8.8
通讯作者：
Qiao L
中科院分区：
文献类型：
--
作者：
Gambino F Jr;Tai W;Voronin D;Zhang Y;Zhang X;Shi J;Wang X;Wang N;Du L;Qiao L
由于疫苗诱导的非中和抗体可能导致寨卡病毒(ZIKV)感染的抗体依赖性增强，我们测试了一种只诱导特定细胞毒性T淋巴细胞(CTL)而不诱导特定抗体的疫苗。我们构建了表达泛素化和重排的ZIKV非结构蛋白3(NS3)的DNA疫苗。蛋白质立即被降解，并在蛋白酶体中加工，通过主要组织相容性复合体(MHC)I类呈递，用于CTL生成。我们用泛素/−/−疫苗免疫Ifnar1/NS3成年小鼠，使它们受孕，并用ZIKV攻击它们。我们的数据显示，该疫苗极大地降低了成年小鼠生殖器官和其他组织中的病毒滴度。用该疫苗免疫的小鼠在ZIKV攻击后全部存活。该疫苗显著减少了胎盘损害和促炎细胞因子水平，并充分保护胎儿免受损害。耗竭实验证明，CD8+CTL在保护中是必不可少的。我们的研究为开发安全有效的病毒感染疫苗提供了一种策略。非中和抗体已被证明可以增强黄病毒的病毒感染。甘比诺等人。寻求一种疫苗策略，既能预防寨卡病毒，又不会诱导抗体。他们证明，仅诱导NS3特异性CTL的ZIKV疫苗可完全保护小鼠免受ZIKV攻击，并保护怀孕小鼠免受胎儿损伤。
As vaccine-induced non-neutralizing antibodies may cause antibody-dependent enhancement of Zika virus (ZIKV) infection, we test a vaccine that induces only specific cytotoxic T lymphocytes (CTLs) without specific antibodies. We construct a DNA vaccine expressing a ubiquitinated and rearranged ZIKV non-structural protein 3 (NS3). The protein is immediately degraded and processed in the proteasome for presentation via major histocompatibility complex (MHC) class I for CTL generation. We immunize Ifnar1−/− adult mice with the ubiquitin/NS3 vaccine, impregnate them, and challenge them with ZIKV. Our data show that the vaccine greatly reduces viral titers in reproductive organs and other tissues of adult mice. All mice immunized with the vaccine survived after ZIKV challenge. The vaccine remarkably reduces placenta damage and levels of pro-inflammatory cytokines, and it fully protects fetuses from damage. CD8+ CTLs are essential in protection, as demonstrated via depletion experiments. Our study provides a strategy to develop safe and effective vaccines against viral infections. Non-neutralizing antibodies have been shown to enhance viral infection in flaviviruses. Gambino et al. sought a vaccine strategy that protects against ZIKV without inducing antibodies. They demonstrate that a ZIKV vaccine inducing solely NS3-specific CTLs provides full protection against ZIKV challenge and protects against fetal damage in pregnant mice.
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影响因子：
30.5
作者：
Dejnirattisai W;Supasa P;Wongwiwat W;Rouvinski A;Barba-Spaeth G;Duangchinda T;Sakuntabhai A;Cao-Lormeau VM;Malasit P;Rey FA;Mongkolsapaya J;Screaton GR
通讯作者：
Screaton GR
DOI：
10.1056/nejmoa1602412
发表时间：
2016-12-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brasil P;Pereira JP Jr;Moreira ME;Ribeiro Nogueira RM;Damasceno L;Wakimoto M;Rabello RS;Valderramos SG;Halai UA;Salles TS;Zin AA;Horovitz D;Daltro P;Boechat M;Raja Gabaglia C;Carvalho de Sequeira P;Pilotto JH;Medialdea-Carrera R;Cotrim da Cunha D;Abreu de Carvalho LM;Pone M;Machado Siqueira A;Calvet GA;Rodrigues Baião AE;Neves ES;Nassar de Carvalho PR;Hasue RH;Marschik PB;Einspieler C;Janzen C;Cherry JD;Bispo de Filippis AM;Nielsen-Saines K
通讯作者：
Nielsen-Saines K
影响因子：
17.1
作者：
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通讯作者：
Barouch DH
影响因子：
158.5
作者：
Driggers, R. W.;Ho, C. -Y.;Vapalahti, O.
通讯作者：
Vapalahti, O.
DOI：
10.3390/v10090480
发表时间：
2018-09-07
期刊：
Viruses
影响因子：
--
作者：
Delgado FG;Torres KI;Castellanos JE;Romero-Sánchez C;Simon-Lorière E;Sakuntabhai A;Roth C
通讯作者：
Roth C