Department of Biological & Medical Sciences, Oxford Brookes University, Oxford OX3 0BP, UK; Oxford Expression Technologies Ltd, Gipsy Lane, Oxford OX3 0BP, UK; The Pirbright Institute, Ash Road, Woking, Surrey GU24 0NB, UK.
CISA-INIA, Valdeolmos, Madrid, Spain.
Vaccine. 2018 Nov 12;36(46):7003-7010. doi: 10.1016/j.vaccine.2018.09.065. Epub 2018 Oct 8.
African horse sickness is a severe, often fatal, arboviral disease of equids. The control of African horse sickness virus (AHSV) in endemic countries is based currently on the use of live attenuated vaccines despite some biosafety concerns derived from its biological properties. Thus, experimental vaccination platforms have been developed over the years in order to avoid the biosafety concerns associated with the use of attenuated vaccines. Various studies showed that baculovirus-expressed AHSV-VP2 or modified Vaccinia Ankara virus expressing AHSV-VP2 (MVA-VP2) induced virus neutralising antibodies and protective immunity in small animals and horses. AHSV is an antigenically diverse pathogen and immunity against AHS is serotype-specific. Therefore, AHS vaccines for use in endemic countries need to induce an immune response capable of protecting against all existing serotypes. For this reason, current live attenuated vaccines are administered as polyvalent preparations comprising combinations of AHSV attenuated strains of different serotypes. Previous studies have shown that it is possible to induce cross-reactive virus neutralising antibodies against different serotypes of AHSV by using polyvalent vaccines comprising combinations of either different serotype-specific VP2 proteins, or MVA-VP2 viruses. However, these strategies could be difficult to implement if induction of protective immunity is highly dependent on using a two-dose vaccination regime for each serotype the vaccine intends to protect against. In our study, we have tested the protective capacity of MVA-VP2 and baculovirus-expressed VP2 vaccines when a single dose was used. Groups of interferon alpha receptor knock-out mice were inoculated with either MVA-VP2 or baculovirus-expressed VP2 vaccines using one dose or the standard two-dose vaccination regime. After vaccination, all four vaccinated groups were challenged with AHSV and clinical responses, lethality and viraemia compared between the groups. Our results show that complete clinical protection was achieved after a single vaccination with either MVA-VP2 or baculovirus sub-unit VP2 vaccines.
非洲马瘟是一种严重的、常致命的马属动物虫媒病毒病。目前，在流行国家控制非洲马瘟病毒（AHSV）的方法是使用减毒活疫苗，尽管其生物特性带来了一些生物安全方面的担忧。因此，多年来已经开发了实验性疫苗接种平台，以避免与使用减毒疫苗相关的生物安全问题。各种研究表明，杆状病毒表达的 AHSV-VP2 或表达 AHSV-VP2 的改良安卡拉痘苗病毒（MVA-VP2）可在小动物和马中诱导病毒中和抗体和保护免疫。AHSV 是一种抗原多样性病原体，对 AHS 的免疫是血清型特异性的。因此，用于流行国家的 AHS 疫苗需要诱导能够针对所有现有血清型的免疫反应。出于这个原因，目前的减毒活疫苗作为多价制剂使用，其中包含不同血清型的 AHSV 减毒株的组合。以前的研究表明，通过使用包含不同血清型特异性 VP2 蛋白组合的多价疫苗，或 MVA-VP2 病毒，可以诱导针对不同血清型 AHSV 的交叉反应性病毒中和抗体。然而，如果诱导保护免疫高度依赖于针对疫苗打算保护的每种血清型使用两剂免疫接种方案，这些策略可能难以实施。在我们的研究中，我们测试了单次使用 MVA-VP2 和杆状病毒表达 VP2 疫苗的保护能力。用 MVA-VP2 或杆状病毒表达 VP2 疫苗对一组干扰素-α受体敲除小鼠进行单剂量或标准两剂量接种。接种后，所有四组接种疫苗的小鼠均用 AHSV 攻毒，并比较组间的临床反应、死亡率和病毒血症。我们的结果表明，单次接种 MVA-VP2 或杆状病毒亚单位 VP2 疫苗均可完全临床保护。
