E90 subunit vaccine protects mice from Zika virus infection and microcephaly.
E90 subunit vaccine protects mice from Zika virus infection and microcephaly.
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E90 亚单位疫苗可保护小鼠免受寨卡病毒感染和小头畸形。
DOI：
10.1186/s40478-018-0572-7
复制
发表时间：
2018-08-10
影响因子：
7.1
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
Zhu X;Li C;Afridi SK;Zu S;Xu JW;Quanquin N;Yang H;Cheng G;Xu Z
寨卡病毒（ZIKV）因其前所未有的爆发及其与胎儿和新生儿发育中的小头畸形等先天畸形的关联而成为全球威胁。目前尚无有效的疫苗或药物可用于预防或治疗 ZIKV 感染。尽管已经建立了多种疫苗平台，但它们预防先天性小头畸形的有效性尚未得到解决。在此，我们在小鼠模型中测试了一种含有 ZIKV 包膜蛋白 (E90) N 端 450 个氨基酸的亚单位疫苗，用于子宫内或新生儿 ZIKV 感染。在一个模型中，已接种疫苗的母鼠的胚胎在胚胎第 13.5 天时受到了当代 ZIKV 毒株的攻击。另一种模型通过将 ZIKV 直接注射到发育中的大脑中来感染已接种疫苗的母鼠的新生小鼠。与未接种疫苗的对照组相比，该疫苗使胎儿或乳鼠大脑中感染 ZIKV 的细胞大幅减少，并成功预防了小头畸形的发生。此外，即使在免疫后 140 天，E90 也可以保护小鼠免受 ZIKV 感染。这项工作直接证明，怀孕小鼠的免疫可以保护子宫内和新生儿期正在发育的后代大脑免受随后的 ZIKV 感染和小头畸形的影响。它还支持E90亚单位疫苗进一步开发临床试验。本文的在线版本 (10.1186/s40478-018-0572-7) 包含补充材料，可供授权用户使用。
Zika virus (ZIKV) became a global threat due to its unprecedented outbreak and its association with congenital malformations such as microcephaly in developing fetuses and neonates. There are currently no effective vaccines or drugs available for the prevention or treatment of ZIKV infection. Although multiple vaccine platforms have been established, their effectiveness in preventing congenital microcephaly has not been addressed. Herein, we tested a subunit vaccine containing the 450 amino acids at the N-terminus of the ZIKV envelope protein (E90) in mouse models for either in utero or neonatal ZIKV infection. In one model, embryos of vaccinated dams were challenged with a contemporary ZIKV strain at embryonic day 13.5. The other model infects neonatal mice from vaccinated dams by direct injection of ZIKV into the developing brains. The vaccine led to a substantial reduction of ZIKV-infected cells measured in the brains of fetal or suckling mice, and successfully prevented the onset of microcephaly compared to unvaccinated controls. Furthermore, E90 could protect mice from ZIKV infection even at 140 days post-immunization. This work directly demonstrates that immunization of pregnant mice protects the developing brains of offspring both in utero and in the neonatal period from subsequent ZIKV infection and microcephaly. It also supports the further development of the E90 subunit vaccine towards clinical trials. The online version of this article (10.1186/s40478-018-0572-7) contains supplementary material, which is available to authorized users.
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DOI：
10.1126/science.aaf5036
发表时间：
2016-04-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Faria NR;Azevedo RDSDS;Kraemer MUG;Souza R;Cunha MS;Hill SC;Thézé J;Bonsall MB;Bowden TA;Rissanen I;Rocco IM;Nogueira JS;Maeda AY;Vasami FGDS;Macedo FLL;Suzuki A;Rodrigues SG;Cruz ACR;Nunes BT;Medeiros DBA;Rodrigues DSG;Queiroz ALN;da Silva EVP;Henriques DF;da Rosa EST;de Oliveira CS;Martins LC;Vasconcelos HB;Casseb LMN;Simith DB;Messina JP;Abade L;Lourenço J;Alcantara LCJ;de Lima MM;Giovanetti M;Hay SI;de Oliveira RS;Lemos PDS;de Oliveira LF;de Lima CPS;da Silva SP;de Vasconcelos JM;Franco L;Cardoso JF;Vianez-Júnior JLDSG;Mir D;Bello G;Delatorre E;Khan K;Creatore M;Coelho GE;de Oliveira WK;Tesh R;Pybus OG;Nunes MRT;Vasconcelos PFC
通讯作者：
Vasconcelos PFC
影响因子：
64.8
作者：
Larocca, Rafael A.;Abbink, Peter;Peron, Jean Pierre S.;Zanotto, Paolo M. de A.;Iampietro, M. Justin;Badamchi-Zadeh, Alexander;Boyd, Michael;Ng'ang'a, David;Kirilova, Marinela;Nityanandam, Ramya;Mercado, Noe B.;Li, Zhenfeng;Moseley, Edward T.;Bricault, Christine A.;Borducchi, Erica N.;Giglio, Patricia B.;Jetton, David;Neubauer, George;Nkolola, Joseph P.;Maxfield, Lori F.;De La Barrera, Rafael A.;Jarman, Richard G.;Eckels, Kenneth H.;Michael, Nelson L.;Thomas, Stephen J.;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
氯喹是 FDA 批准的药物，可预防寨卡病毒感染及其相关的小鼠先天性小头畸形
影响因子：
11.1
作者：
Li C;Zhu X;Ji X;Quanquin N;Deng YQ;Tian M;Aliyari R;Zuo X;Yuan L;Afridi SK;Li XF;Jung JU;Nielsen-Saines K;Qin FX;Qin CF;Xu Z;Cheng G
通讯作者：
Cheng G
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：
19
作者：
Musso, D.;Nhan, T.;Broult, J.
通讯作者：
Broult, J.