Université Paris Sud, UMR 1184, Orsay, France.
CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT center.
JCI Insight. 2017 Mar 23;2(6):e83527. doi: 10.1172/jci.insight.83527.
Chikungunya virus (CHIKV) is rapidly spreading across the globe, and millions are infected. Morbidity due to this virus is a serious threat to public health, but at present, there is no vaccine against this debilitating disease. We have recently developed a number of vaccine candidates, and here we have evaluated 3 of them in a nonhuman primate model. A single immunization with an attenuated strain of CHIKV (Δ5nsP3), a homologous prime-boost immunization with a DNA-launched RNA replicon encoding CHIKV envelope proteins (DREP-E), and a DREP-E prime followed by a recombinant modified vaccinia virus Ankara encoding CHIKV capsid and envelope (MVA-CE) boost all induced protection against WT CHIKV infection. The attenuated Δ5nsP3 virus proved to be safe and did not show any clinical signs typically associated with WT CHIKV infections such as fever, skin rash, lymphopenia, or joint swelling. These vaccines are based on an East/Central/South African strain of Indian Ocean lineage, but they also generated neutralizing antibodies against an isolate of the Asian genotype that now is rapidly spreading across the Americas. These results form the basis for clinical development of an efficacious CHIKV vaccine that generates both humoral and cellular immunity with long-term immunological memory.
基孔肯雅热病毒（CHIKV）正在全球迅速传播，数百万人感染。这种病毒引起的发病率对公共卫生构成严重威胁，但目前尚无针对这种使人衰弱的疾病的疫苗。我们最近开发了一些疫苗候选物，在这里我们在非人类灵长类动物模型中评估了其中的 3 种。用减毒的 CHIKV 株（Δ5nsP3）进行单次免疫接种、用编码 CHIKV 包膜蛋白的 DNA 启动的 RNA 复制子进行同源初免-加强免疫接种（DREP-E），以及用编码 CHIKV 衣壳和包膜的重组改良安卡拉痘苗病毒（MVA-CE）进行 DREP-E 初免后加强免疫，均可诱导针对野生型 CHIKV 感染的保护。减毒的Δ5nsP3 病毒被证明是安全的，没有显示出与野生型 CHIKV 感染相关的任何临床症状，如发热、皮疹、淋巴细胞减少或关节肿胀。这些疫苗基于印度洋谱系的东/中/南非株，但它们也针对现在正在迅速传播到美洲的亚洲基因型分离株产生了中和抗体。这些结果为开发有效的 CHIKV 疫苗奠定了基础，该疫苗可产生体液和细胞免疫，并具有长期的免疫记忆。
