VLP Vaccine Technology

描述（由申请方提供）：病毒样颗粒（VLP）为开发针对高致病性病毒病原体的未来疫苗提供了巨大潜力。VLP在结构和形态上模拟病毒，但无感染性，具有高安全性。我们提出的项目的目标是开发基于重组VLP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。目前尚无针对RSV的许可疫苗。在幼儿中，RSV死亡人数是流感死亡人数的9倍。许可的RSV药物基于抗体的事实高度支持开发有效RSV疫苗的可能性。我们已经开发了RSV VLP疫苗，从最近的可行性研究中证明其在预防RSV增强型疾病方面是有效的。然而，RSV VLP疫苗技术处于早期开发阶段，需要进行大量研究以提供RSV VLP疫苗的充分临床前有效性数据。我们假设，在我们的可行性研究中开发的RSV VLP疫苗将在诱导针对RSV的保护性免疫方面非常有效。在具体目标1中，我们将专注于获得足够的RSV VLP疫苗概念验证有效性数据，并测试长期免疫和非针递送技术（鼻内、微针皮肤和口服疫苗接种）。至于目标2，我们将通过使用分子佐剂化VLP技术开发抗原靶向疫苗佐剂系统并测试许可的佐剂。此外，利用VLP疫苗技术，我们已经开发了一种有前途的通用流感VLP疫苗，并获得了足够的概念验证有效性数据，这有望显着改善目前基于鸡蛋基质的流感疫苗。在目标3中，我们将VLP疫苗的临床前有效性试验扩展到棉鼠（RSV VLP）和雪貂（新型通用流感VLP）。本申请中提出的VLP疫苗将提供一个很好的系统来证明VLP疫苗技术也适用于其他生物防御病原体。

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.