An adenovirus serotype 2-vectored ebolavirus vaccine generates robust antibody and cell-mediated immune responses in mice and rhesus macaques.
An adenovirus serotype 2-vectored ebolavirus vaccine generates robust antibody and cell-mediated immune responses in mice and rhesus macaques.
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腺病毒血清型 2 载体埃博拉病毒疫苗可在小鼠和恒河猴中产生强大的抗体和细胞介导的免疫反应。
DOI：
10.1038/s41426-018-0102-5
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发表时间：
2018-06-06
影响因子：
13.2
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Feng Y;Li C;Hu P;Wang Q;Zheng X;Zhao Y;Shi Y;Yang S;Yi C;Feng Y;Wu C;Qu L;Xu W;Li Y;Sun C;Gao FG;Xia X;Feng L;Chen L
基于几种腺病毒载体的埃博拉病毒疫苗已在临床前研究和临床试验中进行了调查。使用血清2型腺病毒作为埃博拉病毒疫苗载体尚无报道。在此，我们生成了rAd2-ZGP，一种表达密码子优化的扎伊尔埃博拉病毒糖蛋白的重组复制无能腺病毒血清2型，并评估了其在小鼠和恒河猴中的免疫原性。rAd2-ZGP在单次免疫后2周诱导了显著的抗体和细胞介导的免疫应答。糖蛋白（GP）特异性免疫反应可通过加强免疫进一步增强。与蛋白抗原、扎伊尔埃博拉病毒GP和扎伊尔埃博拉病毒样颗粒相比，rAd2-ZGP能在小鼠和恒河猴体内诱导更强的异源苏丹埃博拉病毒交叉反应抗体和细胞介导的免疫应答。在rad2 - zgp免疫的猕猴中，gp特异性CD8+ T细胞可以分泌IFN-γ和IL-2，表明th1偏向性反应。在5型腺病毒血清阳性的猕猴中，rAd2-ZGP能诱导出强大的抗体和细胞介导的免疫应答，表明rAd2-ZGP的效果不受5型腺病毒预先免疫的影响。这些结果表明，rAd2-ZGP可被认为是一种替代的埃博拉病毒疫苗，用于腺病毒血清5型阳性受试者，或在受试者接种了重组腺病毒血清5型疫苗后作为顺序加强疫苗。
Ebolavirus vaccines based on several adenoviral vectors have been investigated in preclinical studies and clinical trials. The use of adenovirus serotype 2 as a vector for ebolavirus vaccine has not been reported. Herein, we generated rAd2-ZGP, a recombinant replication-incompetent adenovirus serotype 2 expressing codon-optimized Zaire ebolavirus glycoprotein, and evaluated its immunogenicity in mice and rhesus macaques. rAd2-ZGP induced significant antibody and cell-mediated immune responses at 2 weeks after a single immunization. The glycoprotein (GP)-specific immune responses could be further enhanced with a booster immunization. Compared to protein antigens, Zaire ebolavirus GP and Zaire ebolavirus-like particles, rAd2-ZGP could induce stronger cross-reactive antibody and cell-mediated immune responses to heterologous Sudan ebolavirus in mice and rhesus macaques. In rAd2-ZGP-immunized macaques, GP-specific CD8+ T cells could secret IFN-γ and IL-2, indicating a Th1-biased response. In adenovirus serotype 5 seropositive macaques, rAd2-ZGP could induce robust antibody and cell-mediated immune responses, suggesting that the efficacy of rAd2-ZGP is not affected by pre-existing immunity to adenovirus serotype 5. These results demonstrated that rAd2-ZGP can be considered an alternative ebolavirus vaccine for use in adenovirus serotype 5 seropositive subjects or as a sequential booster vaccine after the subjects have been immunized with a recombinant adenovirus serotype 5-based vaccine.
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影响因子：
64.8
作者：
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Nabel GJ
影响因子：
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影响因子：
5
作者：
Mellquist-Riemenschneider, JL;Garrison, AR;Schmaljohn, CS
通讯作者：
Schmaljohn, CS
影响因子：
4.9
作者：
Choi JH;Jonsson-Schmunk K;Qiu X;Shedlock DJ;Strong J;Xu JX;Michie KL;Audet J;Fernando L;Myers MJ;Weiner D;Bajrovic I;Tran LQ;Wong G;Bello A;Kobinger GP;Schafer SC;Croyle MA
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