Development of an RSV vaccine for the elderly

开发针对老年人的 RSV 疫苗

• 批准号: 10349499
• 负责人: Trudy G. Morrison
• 金额: $ 72.2万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-02 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10349499
• 关键词: Adjuvant; Adult; Affinity; Age; Aging; Animal Model; Animals; Antibodies; Antibody titer measurement; Avidity; Birds; Bone Marrow; Cessation of life; Clinical Trials; Core Protein; Cotton Rats; Data; Developed Countries; Development; Dose; Elderly; Failure; G-substrate; GTP-Binding Proteins; Goals; Hospitalization; Human; Immune; Immune response; Immunization; Immunize; Immunologics; Influenza; Memory; Memory B-Lymphocyte; Modeling; Mus; Newcastle disease virus; Plasma Cells; Population; Preparation; Proteins; Protocols documentation; Public Health; Reporting; Reproducibility; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory syncytial virus; Respiratory syncytial virus RSV F proteins; Route; Serum; Testing; Time; Vaccine Clinical Trial; Vaccines; Viral Proteins; Virus-like particle; base; design; experience; experimental study; human model; influenzavirus; memory recall; neutralizing antibody; novel; novel vaccines; novel virus; offspring; pathogen; population health; prototype; response; senescence; vaccination protocol; vaccine candidate; vaccine efficacy; vaccine safety

The long-term goal of this project is to develop respiratory syncytial virus (RSV) vaccine candidates for elderly populations. RSV is a significant pathogen of the elderly rivaling influenza in its impact on the health of this population. Currently it is estimated that RSV infections in the elderly result in 11,000 to 17,000 deaths per year in the US and ten times that number of RSV associated hospitalizations. The worldwide population over age 60 is predicted to reach 2.1 billion by 2050, more than a 20% increase over the current number. Such an expansion in this population over the next few decades will pose a greatly increased public health burden making development of elderly RSV vaccines an important priority. This project will develop novel virus-like particles (VLPs) as an RSV vaccine for elderly populations. These VLPs contain the RSV pre-fusion F protein and the G protein and are built on the core proteins of the avian Newcastle Disease Virus. They have been shown to be an effective vaccine in mice and cotton rats (CR). Importantly, they induce high titers of anti-RSV neutralizing antibody titers in animals previously infected with RSV (RSV primed), which mimics the adult human population. They are also effective as a maternal vaccine protecting offspring of immunized animals from RSV challenge. In this project, we hypothesize that using an immunologically superior form of VLP associated pre-F RSV protein in a reproducible and representative human model of RSV infections, we will be able to produce enhanced protective RSV immune responses in the elderly that will surpass those of standard pre-F RSV protein vaccines. Using RSV experienced, elderly cotton rats as human surrogates, we propose three specific aims to develop these VLPs as an RSV vaccine for elderly populations. Aim 1: to ascertain if pre-fusion F VLP immunization of elderly CRs will recall RSV memory induced in young CRs. Aim 2: to determine if pre-fusion F VLP immunization of RSV primed, young CRs can result in protective antibodies in elderly CR with or without a second VLP boost immunization. Aim 3: to assess if VLP induced protective responses in elderly CRs can be further augmented by adjusted doses of VLPs, route of immunization, or addition of adjuvants.

该项目的长期目标是开发呼吸道合胞病毒（RSV）候选疫苗， 老年人口。RSV是老年人的重要病原体，其对健康的影响与流感相当。 这个人口。目前，据估计，老年人中的RSV感染导致11，000至17，000例死亡， 在美国，这一数字是RSV相关住院人数的10倍。全球人口超过 预计到2050年，60岁的老年人将达到21亿，比目前的人数增加20%以上。这样的 在未来几十年内，这一人群的扩张将大大增加公共卫生负担 使老年RSV疫苗的开发成为重要的优先事项。 该项目将开发新型病毒样颗粒（VLP）作为老年人群的RSV疫苗。 这些VLP含有RSV融合前F蛋白和G蛋白，并且构建在RSV融合蛋白的核心蛋白上。 禽纽卡斯尔病病毒。它们已被证明是小鼠和棉鼠的有效疫苗 的双曲余切值。重要的是，它们在先前感染的动物中诱导高滴度的抗RSV中和抗体滴度 用RSV（RSV致敏），其模拟成年人群体。它们也是有效的产妇 保护免疫动物后代免受RSV攻击的疫苗。 在这个项目中，我们假设使用免疫学上上级形式的VLP相关的前F RSV蛋白在RSV感染的可再现和代表性的人类模型中，我们将能够产生 增强老年人的保护性RSV免疫应答，超过标准pre-F RSV 蛋白质疫苗 使用RSV经验丰富的老年棉鼠作为人类替代品，我们提出了三个具体目标， 开发这些VLP作为老年人群的RSV疫苗。 目的1：确定老年CR的融合前F VLP免疫是否会回忆起在哺乳动物中诱导的RSV记忆。 年轻的CR 目的2：为了确定RSV致敏的融合前F VLP免疫，年轻的CR是否可以导致 在有或没有第二次VLP加强免疫的老年CR中的保护性抗体。 目的3：评估老年CR中VLP诱导的保护性反应是否可以通过以下方法进一步增强： 调整VLP剂量、免疫途径或添加佐剂。