A Novel Poxvirus-Based Vaccine, MVA-CHIKV, Is Highly Immunogenic and Protects Mice against Chikungunya Infection
A Novel Poxvirus-Based Vaccine, MVA-CHIKV, Is Highly Immunogenic and Protects Mice against Chikungunya Infection
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DOI：
10.1128/jvi.03418-13
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发表时间：
2014-03-01
影响因子：
5.4
通讯作者：
Esteban, Mariano
中科院分区：
文献类型：
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作者：
Garcia-Arriaza, Juan;Cepeda, Victoria;Esteban, Mariano
需要开发一种针对新出现的基孔肯雅病毒（CHIKV）的单一且高效的疫苗，该病毒会导致人类严重疾病。在这里，我们基于表达 CHIKV C、E3、E2、6K 和 E1 结构基因（称为 MVA-CHIKV）的高度减毒痘病毒载体改良痘苗病毒安卡拉（MVA），生成并表征了新型 CHIKV 候选疫苗的免疫原性特征和功效。 MVA-CHIKV 在细胞培养物中稳定，表达 CHIKV 结构蛋白，并在受感染的人类细胞中引发高尔基体衍生膜的细胞质积累。此外，MVA-CHIKV 在人类巨噬细胞和单核细胞衍生的树突状细胞中引发强烈的先天免疫反应，产生 β 干扰素 (IFN-(1)、促炎细胞因子和趋化因子。用同源方案 (MVA-CHIKV/MVA-CHIKV) 免疫 C57BL/6 小鼠后，产生强、广泛、多功能且持久的 CHIKV 特异性 CD8(+) T 细胞显着地诱导了针对E1和E2蛋白的CHIKV特异性CD8 (+) T细胞，并且在较小程度上还诱导了主要效应记忆表型的CHIKV特异性CD8 (+)记忆T细胞，因为MVA-CHIKV引发了高滴度的针对CHIKV的中和抗体。 MVA-CHIKV 在接受 CHIICV 高剂量攻击后可保护所有小鼠。 总之，MVA-CHIKV 是一种有效的针对基孔肯雅病毒感染的疫苗，可诱导强烈、广泛、高度多功能且持久的 CHIKV 特异性 CD8(+) T 细胞反应，以及针对 CHIKV 的中和抗体。这些结果支持了 MVA-CHIKV 作为针对 CHIKV 的潜在候选疫苗的考虑。
There is a need to develop a single and highly effective vaccine against the emerging chikungunya virus (CHIKV), which causes a severe disease in humans. Here, we have generated and characterized the immunogenicity profile and the efficacy of a novel CHIKV vaccine candidate based on the highly attenuated poxvirus vector modified vaccinia virus Ankara (MVA) expressing the CHIKV C, E3, E2, 6K, and E1 structural genes (termed MVA-CHIKV). MVA-CHIKV was stable in cell culture, expressed the CHIKV structural proteins, and triggered the cytoplasmic accumulation of Golgi apparatus-derived membranes in infected human cells. Furthermore, MVA-CHIKV elicited robust innate immune responses in human macrophages and monocy-te-derived dendritic cells, with production of beta interferon (IFN-(1), proinflammatory cytokines, and chemokines. After immunization of C57BL/6 mice with a homologous protocol (MVA-CHIKV/MVA-CHIKV), strong, broad, polyfunctional, and durable CHIKVspecific CD8(+) T cell responses were elicited. The CHIKV-specific CD8(+) T cells were preferentially directed against El and E2 proteins and, to a lesser extent, against C protein. CHIKV-specific CD8(+) memory T cells of a mainly effector memory phenotype were also induced. The humoral arm of the immune system was significantly induced, as MVA-CHIKV elicited high titers of neutralizing antibodies against CHIKV. Remarkably, a single dose of MVA-CHIKV protected all mice after a high-dose challenge with CHIICV. In summary, MVA-CHIKV is an effective vaccine against chikungunya virus infection that induced strong, broad, highly polyfunctional, and long-lasting CHIKV-specific CD8(+) T cell responses, together with neutralizing antibodies against CHIKV. These results support the consideration of MVA-CHIKV as a potential vaccine candidate against CHIKV.