Development of VLP vaccine for RSV

RSV VLP 疫苗的开发

基本信息

批准号：
9334692
负责人：
JORGE C BLANCO
金额：
$ 93.4万
依托单位：
SIGMOVIR BIOSYSTEMS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-15 至 2019-03-19
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9334692
关键词：
5 year old Accounting Acute Adjuvant Affect Age Age-Months Age-Years Animal Model Animals Antibodies Antibody titer measurement Biological Child Clinical Trials Core Protein Cotton Rats Data Development Disease Dose Elderly Epitopes Fetus Formalin Formulation Future G-substrate GTP-Binding Proteins Generations Goals Health Histology Hospitalization Human Immune response Immune system Immunization Infant Infection Lower Respiratory Tract Infection Lung Lung diseases Maternal antibody Measures Membrane Modeling Molecular Conformation Mothers Mus Mutation Newborn Infant Newcastle disease virus Nose Phase Population Populations at Risk Preclinical Testing Probability Proteins Resources Respiratory Syncytial Virus Infections Respiratory Syncytial Virus Vaccines Respiratory Tract Infections Respiratory syncytial virus Respiratory syncytial virus RSV F proteins Route Safety Serum Small Business Technology Transfer Research Target Populations Testing Tissues Upper Respiratory Infections Upper respiratory tract Vaccinated Vaccination Vaccine Clinical Trial Vaccines Virus Virus Diseases Virus Replication Virus-like particle Vulnerable Populations age group attributable mortality burden of illness cross reactivity experience juvenile animal maternal vaccination neonate neutralizing antibody novel offspring particle pathogen phase 2 study preclinical development public health relevance pup response vaccination strategy vaccine candidate vaccine delivery vaccine efficacy vaccine safety virus development young adult

项目摘要

DESCRIPTION (provided by applicant): Respiratory syncytial virus (RSV) is a substantial threat to human health most severely affecting three large populations, infants, young children, and the elderly. Despite the significance of RSV disease in these different populations, there are no vaccines available. The goal of this Phase II STTR project is to continue preclinical testing of a novel RSV vaccine candidate, a candidate unlike any previously tested. This candidate is a virus-like particle (VLP) built on the Newcastle disease virus core proteins, M and NP, and containing the RSV/A F and G proteins inserted into the membrane of the particle. The objective is to determine the potential of VLPs as a vaccine for each of the human populations at risk for serious disease using well-characterized cotton rats models as surrogates for these groups. Specific aim 1: Optimize protective responses in young animals. Children from 2-5 years of age comprise a substantial proportion of RSV illness burden and likely provide a reservoir for infection of newborns. This age group is considered to have less safety constrains than the newborn, 0-6 month age group, and is, most likely, the population where direct vaccination should be seriously considered. Thus for use of VLPs as a vaccine for this population, the immune responses in young animals will be optimized by testing different routes of VLP delivery and options for VLP formulations for cross protection from RSV/B infections. Specific aim 2: Determine the efficacy of maternal immunization in protection of neonates Direct vaccination of neonates is likely ineffective due to the immaturity of their immune system, safety concerns, and inhibition of vaccine protection by maternal antibodies. An alternative approach is protection of newborns from RSV infections through maternal vaccination that will enhance and extend passive transfer of maternal neutralizing antibodies to the fetus. Thus, the protection of cotton rat pups by VLP vaccination of naïve and RSV experienced mothers will be measured by virus titer in the pups' lungs and nasal tissue after RSV challenge. In addition, safety of maternal immunization in offspring will be determined by measuring lung histology after RSV challenge of pups. Specific aim 3: Assess efficacy of VLP immunization in elderly populations Elderly immune systems are less vigorous than younger adult populations, thus the responses to a vaccine candidate may be different than those of younger adults. Furthermore, the elderly population has experienced RSV infections in their lifetime. Therefore the protection of both naïve and RSV experienced elderly cotton rats by different doses and routes of VLP immunization will be assessed by serum responses and virus titers in lungs after virus challenge to evaluate different strategies of vaccination in this population

描述（由申请人提供）：呼吸道合胞病毒（RSV）对人类健康构成重大威胁，对婴儿、幼儿和老年人这三类人群影响最严重。第二阶段 STTR 项目的目标是继续进行临床前测试。一种新型 RSV 候选疫苗，与之前测试的任何候选疫苗不同，该候选疫苗是一种基于新城疫病毒核心蛋白 M 和 NP 的病毒样颗粒 (VLP)，并含有插入膜中的 RSV/A F 和 G 蛋白。目的是使用特征明确的棉鼠模型作为这些群体的替代品，确定 VLP 作为每种患有严重疾病风险的人群的疫苗的潜力。孩子们来自2-5 岁年龄组占 RSV 疾病负担的很大一部分，并且可能为新生儿感染提供了储存库，该年龄组被认为比 0-6 个月年龄组的新生儿具有更少的安全限制，并且很可能是这样。，应认真考虑直接接种疫苗的人群，因此，为了使用 VLP 作为该人群的疫苗，将通过测试不同的 VLP 递送途径和交叉保护 RSV/VLP 制剂的选择来优化幼年动物的免疫反应。 B 感染。具体目标2：确定母体免疫接种对新生儿保护的效果由于免疫系统不成熟、安全性问题以及母体抗体抑制疫苗保护，直接给新生儿接种疫苗可能无效。另一种方法是保护新生儿免受 RSV 感染。通过母体疫苗接种，将增强和延长母体中和抗体向胎儿的被动转移。因此，通过未接种过 VLP 疫苗和经历过 RSV 的母亲接种 VLP 对棉鼠幼仔的保护作用将通过体内的病毒滴度来衡量。此外，RSV 攻击后幼犬的肺部和鼻组织的安全性将通过测量幼犬 RSV 攻击后的肺组织学来确定。具体目标 3：评估老年人群中 VLP 免疫的效果。与年轻人相比，因此对候选疫苗的反应可能与年轻人不同。此外，老年人在一生中经历过 RSV 感染，因此对幼年棉鼠和 RSV 的保护经历不同。 VLP免疫的剂量和途径将通过病毒攻击后的血清反应和肺部病毒滴度来评估，以评估该人群的不同疫苗接种策略