Human Enterovirus 71 empty capsids produced by baculovirus expression as vaccines

在西方国家，人类肠道病毒71型会导致儿童时期轻度发烧疾病的流行暴发。偶尔会出现并发症，但通常认为这种病毒是无害的，只由卫生当局定期监测。然而，在远东地区，EV71的暴发与严重感染和脑炎发病率的增加有关。目前尚不清楚这是因为传播的特定菌株造成的，还是人群的遗传倾向于一个严重的结果。无论是哪种情况，EV71型疫苗都将是一项有价值的预防措施。已经对生产疫苗的许多可能性进行了审查，但到目前为止，所有这些可能性都未能提供高水平的保护性免疫。被检查的候选人中的一员？空衣人？疫苗是真正的EV71病毒颗粒的安全非传染性版本，已被证明是最有希望的。然而，空衣壳很难制造，这使得它们能否发展成为一种有市场的疫苗是不确定的。我们已经开发了一种新的方法，可以高产量地重复生产空衣壳，为生产提供了一条潜在的可行路线。在这项申请中，我们试图将这项技术应用于生产EV71型空衣壳疫苗，并证明其在产生保护性免疫方面的成功。这项工作将与英国健康保护局和总部设在马来西亚的Sentinext公司合作完成，这两家公司正在积极研究区域毒株和疫苗开发。

Human enterovirus 71 causes epidemic outbreaks of mild febrile illness during childhood in Western countries. There are occasional complications but the virus is generally assumed to be innocuous and is only monitored periodically by the health authorities. In the Far East however, EV71 outbreaks are associated with an increased incidence of severe infection and encephalitis. It is unclear if this is because of the particular strains that circulate or if the genetics of the population favour a severe outcome. In either case a vaccine for EV71 would be a valuable preventive measure. A number of possibilities have been examined for production of a vaccine but all have so far failed to give a high level of protective immunity. Of the candidates examined ?empty capsid? vaccines, which are a safe non-infectious version of the authentic EV71 virus particle, have been shown to be the most promising. However, empty capsids are difficult to manufacture making their development to a marketable vaccine unsure. We have developed a new methodology that reproducibly produces empty capsid at high yield offering a potentially viable route for manufacture. In this application we are seeking to apply this technology to the production of an empty capsid vaccine for EV71 and to demonstrate its success in the generation of protective immunity. The work will be done in collaboration with the UK Health Protection Agency and the company Sentinext, based in Malaysia, who are actively working with regional strains and vaccine development.