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

1998- 1999年马来西亚和新加坡第一次也是最严重的尼帕病毒暴发是由猪到人的传播造成的。此次疫情通过扑杀马来西亚近一半的生猪得到了控制，这对当地养猪业造成了严重和持久的经济损失。尽管新冠病毒对世界上一些猪群最密集的地区构成威胁，但目前尚无疫苗可用。新冠病毒疫苗的商业开发是有限的，因为动物保健公司认为，由于外溢疫情的偶发性，新冠病毒疫苗的可销售性有限。为了弥补这一差距，我们正在开发一种猪用疫苗，以减少NiV对养猪业、牲畜饲养者和公共卫生构成的风险。我们已经证明，用NiV G或F糖蛋白免疫猪，使用两次免疫制度，提供了对NiV的高水平保护。然而，当猪在一次免疫接种后受到挑战时，这种保护作用就失去了。猪用新冠肺炎疫苗可用于应对紧急疫情情况，或常规用于降低新冠肺炎疫情发生的风险。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要求，这种候选疫苗可以在单次免疫后提供快速免疫，也可以用作二价疫苗。伪狂犬病毒减毒活疫苗是一种高效疫苗，已使伪狂犬病毒从欧洲和美洲大部分地区根除。减毒的伪狂犬病病毒可以很容易地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NiV G和F的减毒活病毒在单次免疫后是否能引起保护性免疫反应。如果成功，这种疫苗也可以作为二价疫苗开发。由于NiV流行地区的猪常规接种了PrV减毒活疫苗，这可能是一种经济上可行的大规模免疫方法，这将显著降低通过猪暴发NiV的风险。预防性和反应性使用NiV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NiV核衣壳、磷蛋白和基质蛋白在感染但未接种疫苗的猪中检测抗体的潜力。

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.