Optimized production and immunogenicity of an insect virus-based chikungunya virus candidate vaccine in cell culture and animal models.
Optimized production and immunogenicity of an insect virus-based chikungunya virus candidate vaccine in cell culture and animal models.
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DOI：
10.1080/22221751.2021.1886598
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发表时间：
2021-12
影响因子：
13.2
通讯作者：
Wang T
中科院分区：
文献类型：
--
作者：
Adam A;Luo H;Osman SR;Wang B;Roundy CM;Auguste AJ;Plante KS;Peng BH;Thangamani S;Frolova EI;Frolov I;Weaver SC;Wang T
以前曾报道过一种嵌合的埃拉特/基孔肯雅病毒（EILV/CHIKV）仅在蚊子细胞中复制，但能够在动物中诱导强大的适应性免疫。在这里，我们最初选择C7/10细胞来优化嵌合病毒的生产。两步程序产生高度纯化的病毒储存，在小鼠致敏研究中显示不会引起过敏反应。我们进一步优化了剂量，并表征了EILV/ chikv诱导免疫的动力学。单剂量108 PFU足以诱导高水平的chikv特异性IgM和IgG抗体，记忆B细胞和CD8+ T细胞反应。与CHIKV减毒活疫苗181/25相比，EILV/CHIKV在第28天诱导了相似水平的CHIKV特异性记忆B细胞，但CD8+ T细胞反应更高。在接种后第55天，它还诱导了比另一种减毒的CHIKV病毒株（CHIKV/IRES）更强的CD8+，但较低的CD4+ T细胞反应。最后，纯化的EILV/CHIKV在体内触发抗病毒细胞因子反应和抗原提呈细胞（APC）的激活，但在体外暴露时不诱导APC。总的来说，我们的研究结果表明，EILV/CHIKV候选疫苗是安全的，生产成本低廉，并且是小鼠先天性和适应性免疫的有效诱导剂。
A chimeric Eilat/ Chikungunya virus (EILV/CHIKV) was previously reported to replicate only in mosquito cells but capable of inducing robust adaptive immunity in animals. Here, we initially selected C7/10 cells to optimize the production of the chimeric virus. A two-step procedure produced highly purified virus stocks, which was shown to not cause hypersensitive reactions in a mouse sensitization study. We further optimized the dose and characterized the kinetics of EILV/CHIKV-induced immunity. A single dose of 108 PFU was sufficient for induction of high levels of CHIKV-specific IgM and IgG antibodies, memory B cell and CD8+ T cell responses. Compared to the live-attenuated CHIKV vaccine 181/25, EILV/CHIKV induced similar levels of CHIKV-specific memory B cells, but higher CD8+ T cell responses at day 28. It also induced stronger CD8+, but lower CD4+ T cell responses than another live-attenuated CHIKV strain (CHIKV/IRES) at day 55 post-vaccination. Lastly, the purified EILV/CHIKV triggered antiviral cytokine responses and activation of antigen presenting cell (APC)s in vivo, but did not induce APCs alone upon in vitro exposure. Overall, our results demonstrate that the EILV/CHIKV vaccine candidate is safe, inexpensive to produce and a potent inducer of both innate and adaptive immunity in mice.
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影响因子：
5.5
作者：
Brandler, Samantha;Ruffle, Claude;Tangy, Frederic
通讯作者：
Tangy, Frederic
影响因子：
7.3
作者：
Broeckel, Rebecca M.;Haese, Nicole;Streblow, Daniel N.
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Streblow, Daniel N.
影响因子：
5.4
作者：
Hallengard, David;Lum, Fok-Moon;Liljestrom, Peter
通讯作者：
Liljestrom, Peter
影响因子：
5.4
作者：
Gorchakov, Rodion;Wang, Eryu;Weaver, Scott C.
通讯作者：
Weaver, Scott C.
影响因子：
4.4
作者：
Collins, C;Wolfe, J;Budd, RC
通讯作者：
Budd, RC