Human Enterovirus 71 empty capsids produced by baculovirus expression as vaccines

人类肠道病毒71型在西方国家引起儿童期轻度发热性疾病的流行性暴发。偶尔会有并发症，但病毒通常被认为是无害的，只由卫生当局定期监测。然而，在远东，EV71的爆发与严重感染和脑炎的发病率增加有关。目前还不清楚这是因为传播的特定菌株，还是人口的遗传学有利于严重的结果。在任何一种情况下，EV71疫苗都是一种有价值的预防措施。已经研究了生产疫苗的许多可能性，但到目前为止，所有这些都未能产生高水平的保护性免疫力。候选人名单？空衣壳疫苗是真正的EV71病毒颗粒的安全的非感染性版本，已被证明是最有希望的。然而，空衣壳难以制造，使得它们开发成可销售的疫苗不确定。我们已经开发了一种新的方法，可重复地生产空衣壳在高产量提供了一个潜在的可行的生产路线。在本申请中，我们试图将该技术应用于EV71的空衣壳疫苗的生产，并证明其在产生保护性免疫方面的成功。这项工作将与英国卫生保护局和总部位于马来西亚的Sentinext公司合作完成，他们正在积极研究区域菌株和疫苗开发。

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.