A live attenuated pseudorabies virus vectored Nipah vaccine for enhanced protection in pigs

猪与人之间的传播是1998-1999年马来西亚和新加坡第一次也是最严重的尼帕病毒(Nipah Virus，NIV)暴发的原因。这次疫情是通过扑杀马来西亚近一半的生猪得到控制的，这对当地养猪业造成了严重和持久的经济损害。尽管新城疫病毒对世界上一些猪密度最高的地区构成了威胁，但目前还没有疫苗可用。新城疫疫苗的商业开发是有限的，因为动物保健公司认为，由于溢出疫情的零星性质，市场将是有限的。为了弥补这一差距，我们正在开发一种用于猪的疫苗，该疫苗将降低新城疫对养猪业、牲畜饲养者和公共卫生造成的风险。我们已经证明，用新城疫病毒G或F糖蛋白免疫猪，使用两次免疫方案，提供了对新城疫病毒的高水平保护。然而，当猪在一次免疫后受到挑战时，这种保护就会失去。针对猪的新城疫疫苗可用于应对紧急疫情，或常规用于降低新城疫暴发的风险。拟议的项目旨在通过评估一种候选疫苗来满足这两种情况的需求，该候选疫苗可以在单次免疫后提供快速免疫力，也可以用作双价疫苗。伪狂犬病减毒活疫苗(PRV)是一种高效疫苗，能够在欧洲和美洲的大部分地区根除伪狂犬病病毒。减毒活PRV可以很容易地被改造成表达来自其他病原体的抗原，并作为有效的疫苗载体。该项目将评估同时表达新城疫病毒G和F的减毒活PRV在单次免疫后是否能够诱导保护性免疫反应。如果成功，这种疫苗还可以被开发为二价疫苗。由于新城疫流行地区的猪经常接种减毒活PRV疫苗，这可能提供一种经济上可行的大规模免疫接种方法，这将显著降低新城疫通过猪爆发的风险。预防性和反应性使用新城疫疫苗的批准将取决于能够区分受感染动物和接种疫苗动物的诊断测试的可用性。因此，我们将评估重组新城疫病毒核衣壳、磷蛋白和基质蛋白检测感染但未接种疫苗的猪的抗体的潜力。

Pig-to-human transmission was responsible for the first and most severe Nipah virus (NiV) outbreak in Malaysia and Singapore in 1998-99\. This outbreak was controlled by culling almost half of all pigs in Malaysia, which caused severe and lasting economic damage to the local pig industry. Despite the threat NiV poses to some of the most pig dense regions of the world, no vaccines are currently available. Commercial development of NiV vaccines is limited, since animal health companies are of the opinion that there will be limited marketability due to the sporadic nature of spillover outbreaks. To address this gap, we are developing a vaccine for use in pigs that would reduce the risk that NiV poses to the pig industry, livestock keepers and public health. We have demonstrated that immunisation of pigs with either the NiV G or F glycoproteins, using a two-shot immunisation regime, provides a high level of protection against NiV. However, the protection is lost when pigs are challenged after a single immunisation. A NiV vaccine for pigs could be deployed in response to an emergency outbreak situation or routinely used to reduce the risk of NiV outbreaks occurring. The proposed project aims to address the requirements for both scenarios by evaluating a vaccine candidate that may provide rapid immunity after a single immunisation and could also be used as a bivalent vaccine. Live attenuated pseudorabies virus (PrV) vaccines are highly effective vaccines that have enabled the eradication of PrV from large parts of Europe and America. Live attenuated PrV can be readily engineered to express antigens from other pathogens and serve as potent vaccine vectors. This project will evaluate whether live attenuated PrV expressing both NiV G and F can elicit protective immune responses after a single immunisation. If successful, this vaccine could also be exploited as a bivalent vaccine. Since pigs in the NiV endemic region are routinely vaccinated with live attenuated PrV vaccines, this could present an economically viable approach to mass immunisation, which would significantly reduce the risk of NiV outbreaks emerging through pigs. Approvals for both preventative and reactive use NiV vaccines will be reliant on the availability of diagnostic tests that are able to discriminate infected from vaccinated animals. We will therefore evaluate the potential of recombinant NiV nucleocapsid, phosphoprotein, and matrix proteins to detect antibodies in infected but not vaccinated pigs.