ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice.
ChAdOx1 and MVA based vaccine candidates against MERS-CoV elicit neutralising antibodies and cellular immune responses in mice.
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DOI：
10.1016/j.vaccine.2017.05.032
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发表时间：
2017-06-27
期刊：
影响因子：
5.5
通讯作者：
Gilbert SC
中科院分区：
文献类型：
--
作者：
Alharbi NK;Padron-Regalado E;Thompson CP;Kupke A;Wells D;Sloan MA;Grehan K;Temperton N;Lambe T;Warimwe G;Becker S;Hill AVS;Gilbert SC
插入tPA先导序列可增强ChAdOx1 MERS的体液应答。ChAdOx1 MERS引发细胞免疫和中和抗体。ChAdOx1对MVA MERS反应增强。单剂ChAdOx1 MERS的免疫原性相当于2剂MVA MERS。在MVA中，与mH5启动子相比，F11启动子增强了细胞免疫原性，但没有增强体液免疫原性。自2012年以来，中东呼吸综合征冠状病毒（MERS-CoV）已经感染了1900多人。该综合征的范围从无症状和轻度病例到严重肺炎和死亡。据信，该病毒自20世纪80年代以来一直在单峰骆驼中传播，没有明显症状。因此，单峰骆驼被认为是唯一的动物感染源。尽管在这一领域进行了积极的研究，但抗病毒药物和疫苗都没有被批准用于兽医或医疗用途。在此，我们基于ChAdOx1和MVA病毒载体开发了4种针对MERS-CoV的候选疫苗，每个载体两个候选疫苗。所有疫苗均含有MERS-CoV全长刺突基因；ChAdOx1 MERS疫苗有或没有人组织纤溶酶原激活基因（tPA）的先导序列，MVA MERS疫苗有tPA，但mH5或F11启动子驱动刺突基因的表达。在小鼠模型中对所有候选疫苗进行了仅初始或初始增强方案的评估。含tPA的ChAdOx1 MERS诱导的中和抗体高于不含tPA的ChAdOx1 MERS。单剂量的ChAdOx1 MERS与tPA一起引发细胞免疫反应以及中和抗体，MVA MERS显著提高了抗体的水平。单剂量ChAdOx1 MERS合并tPA的体液免疫原性与两剂量MVA MERS（也合并tPA）相当。带有mH5或F11启动子的MVA MERS诱导的抗体水平相似；而F11启动子对MVA - MERS的细胞免疫原性有显著提高。总之，我们的研究表明，MERS-CoV候选疫苗可以通过利用不同的病毒载体、不同的载体遗传设计或不同的方案来优化，以提高免疫原性。ChAdOx1和MVA载体疫苗已在骆驼和人类中进行了安全评估，这些中东呼吸综合征候选疫苗现在应在骆驼和临床试验中进行测试。
Inserting tPA leader sequence enhanced humoral responses of ChAdOx1 MERS. ChAdOx1 MERS elicited cellular immunity and neutralising antibodies. ChAdOx1 MERS responses were boosted by MVA MERS. Immunogenicity of a single dose of ChAdOx1 MERS was equivalent to 2 doses of MVA MERS. In MVA, F11 promoter enhanced cellular, but not humoral, immunogenicity, comparing to mH5 promoter. The Middle East respiratory syndrome coronavirus (MERS-CoV) has infected more than 1900 humans, since 2012. The syndrome ranges from asymptomatic and mild cases to severe pneumonia and death. The virus is believed to be circulating in dromedary camels without notable symptoms since the 1980s. Therefore, dromedary camels are considered the only animal source of infection. Neither antiviral drugs nor vaccines are approved for veterinary or medical use despite active research on this area. Here, we developed four vaccine candidates against MERS-CoV based on ChAdOx1 and MVA viral vectors, two candidates per vector. All vaccines contained the full-length spike gene of MERS-CoV; ChAdOx1 MERS vaccines were produced with or without the leader sequence of the human tissue plasminogen activator gene (tPA) where MVA MERS vaccines were produced with tPA, but either the mH5 or F11 promoter driving expression of the spike gene. All vaccine candidates were evaluated in a mouse model in prime only or prime-boost regimens. ChAdOx1 MERS with tPA induced higher neutralising antibodies than ChAdOx1 MERS without tPA. A single dose of ChAdOx1 MERS with tPA elicited cellular immune responses as well as neutralising antibodies that were boosted to a significantly higher level by MVA MERS. The humoral immunogenicity of a single dose of ChAdOx1 MERS with tPA was equivalent to two doses of MVA MERS (also with tPA). MVA MERS with mH5 or F11 promoter induced similar antibody levels; however, F11 promoter enhanced the cellular immunogenicity of MVA MERS to significantly higher magnitudes. In conclusion, our study showed that MERS-CoV vaccine candidates could be optimized by utilising different viral vectors, various genetic designs of the vectors, or different regimens to increase immunogenicity. ChAdOx1 and MVA vectored vaccines have been safely evaluated in camels and humans and these MERS vaccine candidates should now be tested in camels and in clinical trials.
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影响因子：
13.2
作者：
Ali MA;Shehata MM;Gomaa MR;Kandeil A;El-Shesheny R;Kayed AS;El-Taweel AN;Atea M;Hassan N;Bagato O;Moatasim Y;Mahmoud SH;Kutkat O;Maatouq AM;Osman A;McKenzie PP;Webby RJ;Kayali G
通讯作者：
Kayali G
影响因子：
5
作者：
Lessler, Justin;Salje, Henrik;Cummings, Derek A. T.
通讯作者：
Cummings, Derek A. T.
影响因子：
2.4
作者：
Gossner C;Danielson N;Gervelmeyer A;Berthe F;Faye B;Kaasik Aaslav K;Adlhoch C;Zeller H;Penttinen P;Coulombier D
通讯作者：
Coulombier D
影响因子：
11.8
作者：
Al Hammadi, Zulaikha M.;Chu, Daniel K. W.;Poon, Leo L. M.
通讯作者：
Poon, Leo L. M.
影响因子：
6.4
作者：
Alagaili, Abdulaziz N.;Briese, Thomas;Lipkin, W. Ian
通讯作者：
Lipkin, W. Ian