VLP Vaccine Technology

描述（由申请人提供）：病毒样颗粒（vlp）为开发未来针对高致病性病毒病原体的疫苗提供了巨大潜力。VLPs在结构和形态上与病毒相似，但没有传染性，具有很高的安全性。我们提出的项目目标是开发基于重组VLPs的疫苗技术。呼吸道合胞病毒（RSV）和流感病毒是重要的呼吸道病毒病原体。目前尚无针对呼吸道合胞病毒的许可疫苗。在婴儿中，呼吸道合胞病毒死亡人数是流感死亡人数的9倍。获得许可的RSV药物是基于抗体的，这一事实极大地支持了开发有效RSV疫苗的可能性。从最近的可行性研究中，我们已经开发出RSV VLP疫苗，证明在预防RSV增强疾病方面是有效的。然而，RSV VLP疫苗技术尚处于早期发展阶段，需要大量的研究来提供足够的RSV VLP疫苗的临床前疗效数据。我们假设在我们的可行性研究中开发的RSV VLP疫苗将非常有效地诱导对RSV的保护性免疫。在具体目标1中，我们将侧重于获得足够的RSV VLP疫苗的概念有效性证明数据，以及测试长期免疫和非针头递送技术（鼻内、微针皮肤和口服疫苗接种）。至于目标2，我们将利用分子佐剂VLP技术开发抗原靶向疫苗佐剂系统，并测试许可佐剂。此外，利用VLP疫苗技术，我们开发了一种有前景的通用流感VLP疫苗，并获得了足够的概念有效性验证数据，有望显著改善目前基于鸡蛋底物的流感疫苗。在目标3中，我们将VLP疫苗的临床前疗效试验扩展到棉大鼠（RSV VLPs）和雪貂（新型通用流感VLPs）。本研究提出的VLP疫苗将为VLP疫苗技术在其他生物防御病原体中的应用提供一个良好的体系。

DESCRIPTION (provided by applicant): Virus-like particles (VLPs) provide great potential to develop future vaccines against highly pathogenic viral pathogens. VLPs mimic the virus in structure and morphology, but are non-infectious, featuring a high safety profile. The goal of our proposed project is to develop vaccine technology based on recombinant VLPs. Respiratory syncytial virus (RSV) and influenza virus are important respiratory viral pathogens. There is no licensed vaccine against RSV. There are 9 times more deaths by RSV than those by influenza among young infants. The fact that licensed RSV drugs are based on antibodies highly supports the possibility to develop an effective RSV vaccine. We have developed RSV VLP vaccines that are proven to be effective in preventing RSV enhanced disease from recent feasibility studies. However, RSV VLP vaccine technology is in an early stage of development and much study is needed to provide sufficient preclinical efficacy data of RSV VLP vaccines. We hypothesize that RSV VLP vaccines developed in our feasibility studies will be highly effective in inducing protective immunity against RSV. In the specific aim 1, we will focus on obtaining sufficient proof-of-concept efficacy data of RSV VLP vaccines as well as testing long-term immunity and non-needle delivery technologies (intranasal, microneedle skin, and oral vaccination). As for aim 2, we will develop antigen targeting vaccine adjuvant systems by using molecularly adjuvanted VLP technology and test licensed adjuvants. Also, utilizing VLP vaccine technology, we have developed a promising universal influenza VLP vaccine and obtained sufficient proof-of-concept efficacy data, which is expected to significantly improve the current egg-substrate based influenza vaccines. In the aim 3, we will extend the preclinical efficacy tests of VLP vaccines to cotton rats (RSV VLPs) and ferrets (novel universal influenza VLPs). VLP vaccines proposed in this application will provide an excellent system to prove VLP vaccine technologies which are also applicable to other biodefense pathogens.