VLP Vaccine Technology

VLP疫苗技术

• 批准号: 9198196
• 负责人: SANG-MOO KANG
• 金额: $ 72.63万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-15 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9198196
• 关键词: Adjuvant; Animal Model; Antibodies; Antigen Targeting; Antigen-Presenting Cells; Centers for Disease Control and Prevention (U.S.); Cessation of life; Collaborations; Cotton Rats; Data; Development; Disease; Feasibility Studies; Ferrets; Flagellin; Formalin; Future; Goals; Hepatitis B; Human; IACUC; Immunity; Infant; Influenza; Injection of therapeutic agent; Intramuscular; Ligands; Lung diseases; MF59; Membrane; Methods; Modeling; Molecular; Morphology; Mus; Needles; Oral; Palivizumab; Papillomaviridae; Papillomavirus; Pathogenicity; Pharmaceutical Preparations; Production; Protocols documentation; Public Health; Rattus; Recombinants; Research Personnel; Respiratory Syncytial Virus Vaccines; Respiratory syncytial virus; Safety; Skin; Structure; System; TLR4 gene; Tandem Repeat Sequences; Technology; Testing; Therapeutic; Time; Vaccination; Vaccine Adjuvant; Vaccines; Viral; Virulence; Virus; Virus-like particle; aluminum sulfate; base; biodefense; efficacy evaluation; efficacy testing; egg; immunogenicity; improved; influenza virus vaccine; influenzavirus; mortality; mouse model; new technology; novel; novel vaccines; oral vaccine; pathogen; preclinical efficacy; prevent; product development; protective efficacy; public health relevance; recombinant virus; respiratory; vaccine candidate; vaccine delivery; vaccine development; vaccine efficacy; virus development; virus envelope

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.

描述(由申请人提供)：病毒样颗粒(VLP)为未来开发针对高致病性病毒病原体的疫苗提供了巨大的潜力。VLP在结构和形态上与病毒相似，但不具传染性，具有很高的安全性。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体。目前还没有针对RSV的许可疫苗。在婴儿中，死于RSV的人数是死于流感的人数的9倍。获得许可的RSV药物是以抗体为基础的，这一事实高度支持了开发有效的RSV疫苗的可能性。从最近的可行性研究来看，我们已经开发出在预防RSV增强型疾病方面被证明有效的RSV VLP疫苗。然而，RSV VLP疫苗技术还处于早期发展阶段，需要进行大量的研究来提供足够的RSV VLP疫苗的临床前效力数据。我们推测，在我们的可行性研究中开发的RSV VLP疫苗将在诱导对RSV的保护性免疫方面非常有效。在具体目标1中，我们将侧重于获得足够的RSV VLP疫苗的概念验证效力数据，以及测试长期免疫和非针头注射技术(鼻腔、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，并测试许可的佐剂。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验证效力数据，这有望显著改善目前以鸡蛋为底物的流感疫苗。在目标3中，我们将把VLP疫苗的临床前效力测试扩展到棉花鼠(RSV VLP)和雪貂(新型通用流感VLP)。本申请中提出的VLP疫苗将为验证VLP疫苗技术提供一个很好的系统，该技术也适用于其他生物防御病原体。