Development and testing of RSV vaccines using a computational framework of virus-host interaction
使用病毒-宿主相互作用的计算框架开发和测试 RSV 疫苗
基本信息
- 批准号:10549828
- 负责人:
- 金额:$ 10.17万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-01-21 至 2026-12-31
- 项目状态:未结题
- 来源:
- 关键词:AntibodiesAntibody ResponseAntibody SpecificityAntibody titer measurementAntigensB-LymphocytesBindingBiological AssayBlood group antigen fBody Weight decreasedCellsCessation of lifeChildClinical TrialsCodon NucleotidesComputer AssistedComputer ModelsComputer SimulationDevelopmentDiseaseElderlyEncapsulatedEnzyme-Linked Immunosorbent AssayEpithelial CellsEvaluationFailureFormulationHospitalizationHumanHumoral ImmunitiesImmuneImmune responseImmunityImmunizationImmunizeImmunologyIn VitroInfectionLipidsLungMembrane ProteinsMessenger RNAMonitorMusOutcomePolyvalent VaccineProteinsRecording of previous eventsRespiratory Syncytial Virus VaccinesRespiratory syncytial virusSeverity of illnessSiteSpecificityStructureT-LymphocyteTestingTimeVaccine DesignVaccinesVariantViral ProteinsViral load measurementVirusVirus Diseasesadaptive immune responseantibody testcomputer frameworkcross reactivityenzyme linked immunospot assayimprovedinsightlipid nanoparticlelung histologymouse modelneutralizing antibodypathogenpulmonary functionrespiratory virussimulationvaccine developmentvaccine formulationvirus host interaction
项目摘要
Respiratory Syncytial Virus (RSV) is the second leading cause of hospitalization in children worldwide and has
been increasing appreciated as a cause of hospitalization and death in the elderly. Recent studies have shown
that polyvalent vaccine formulations, mixture of antigens derived from distinct pathogen variants, can induce
antibodies to regions conserved between those variants We hypothesize that polyvalent antigen RSV vaccine
formulations will increase antibody to regions conserved between the antigens. By drawing on the natural
variability that exists among RSV variants, we aim to study the effect that polyvalent RSV G or F antigen
formulations have on the immune response. We will test if antibodies are enhanced towards regions conserved
between the viral proteins with the polyvalent formulation.
Aim 1. Determining the Effect of Polyvalent RSV Vaccine Formulations on Humoral Immunity using
Computer Simulations. We hypothesize that RSV polyvalent vaccine formulations consisting of different
combinations of G or F-protein antigens will increase the antibody response to conserved regions between the
antigens. We will evaluate different vaccine formulations using a computational framework of virus/host-
interaction (ssMod.v2). We will test for differences in antibody specificity between polyvalent and monovalent
formulations in the framework. Antibody cross-reactivity and protection against RSV challenge will also be
evaluated.
Aim 2. Comparison of the Host Immune Response to Polyvalent Vaccine Formulations in Mice. We
hypothesize that murine immunization with a mRNA-LNP vaccine comprising polyvalent antigen formulations
will induce antibodies and immune cells specific to regions conserved between the antigens. mRNA-LNPs will
be constructed using cap-1, codon-optimized, structure-stabilized mRNA, encoding G or F from A2 or B1 RSV
variants and will be encapsulated using ionizable cationic lipids. Groups of mice will be immunized with either
Aim 3. Test if RSV Polyvalent Vaccine Formulation Improves Protection from RSV Disease. We
hypothesize that vaccine formulations containing polyvalent mixtures of G or F antigens will increase the extent
of protection against RSV disease compared to monovalent formulations. Using different mixtures of mRNA-
LNP, we will test the ability of polyvalent vaccines to protect against disease severity using a murine model of
RSV challenge. The neutralizing antibody titer of the sera will be tested using a primary human lung epithelial
cell RSV-neutralization assay. Monovalent and polyvalent vaccine formulations will be compared by testing for
differences between infection and disease severity outcomes.
呼吸道合胞病毒(RSV)是全球儿童住院的第二大原因,
作为老年人住院和死亡的一个原因越来越受到重视。最近的研究表明
多价疫苗制剂,即来自不同病原体变体的抗原混合物,
我们假设多价抗原RSV疫苗
这些制剂将增加针对抗原之间保守区域的抗体。通过利用自然
RSV变异体之间存在的变异性,我们的目的是研究多价RSV G或F抗原
对免疫反应的影响。我们将测试抗体是否对保守区域增强
病毒蛋白质与多价制剂之间的关系。
目标1.使用ELISA测定多价RSV疫苗制剂对体液免疫的影响
计算机模拟。我们假设RSV多价疫苗制剂由不同的
G或F-蛋白抗原的组合将增加对免疫球蛋白之间的保守区域的抗体应答。
抗原我们将使用病毒/宿主的计算框架来评估不同的疫苗制剂,
相互作用(ssMod.v2)。我们将测试多价和单价之间抗体特异性的差异
在框架内制定。抗体交叉反应性和针对RSV攻击的保护也将被考虑。
评估。
目标二。小鼠中宿主对多价疫苗制剂的免疫应答的比较。我们
假设用包含多价抗原制剂mRNA-LNP疫苗免疫鼠
将诱导对抗原之间保守区域特异的抗体和免疫细胞。mRNA-LNP将
使用编码来自A2或B1 RSV的G或F的cap-1、密码子优化的、结构稳定的mRNA构建
变体,并将使用可电离的阳离子脂质包封。将用以下任一种免疫小鼠组
目标3.测试RSV多价疫苗制剂是否改善对RSV疾病的保护。我们
假设含有G或F抗原的多价混合物的疫苗制剂将增加
与单价制剂相比,使用不同的mRNA混合物-
LNP,我们将测试多价疫苗的能力,以保护对疾病的严重程度,使用鼠模型,
RSV攻毒。将使用原代人肺上皮细胞检测血清的中和抗体滴度。
细胞RSV-中和测定。将通过检测以下指标来比较单价和多价疫苗制剂:
感染和疾病严重程度结果之间的差异。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Christopher S Anderson其他文献
Christopher S Anderson的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Christopher S Anderson', 18)}}的其他基金
Development and testing of RSV vaccines using a computational framework of virus-host interaction
使用病毒-宿主相互作用的计算框架开发和测试 RSV 疫苗
- 批准号:
10426748 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别:
相似海外基金
Characterizing the SARS-CoV-2 antibody response and associations with patient factors: Serological profiling of participants enrolled in the GENCOV study
描述 SARS-CoV-2 抗体反应及其与患者因素的关联:参与 GENCOV 研究的参与者的血清学分析
- 批准号:
495256 - 财政年份:2023
- 资助金额:
$ 10.17万 - 项目类别:
Understanding the human antibody response to a malaria transmission-blocking vaccine
了解人类抗体对疟疾传播阻断疫苗的反应
- 批准号:
MR/X009491/1 - 财政年份:2023
- 资助金额:
$ 10.17万 - 项目类别:
Research Grant
Probing the role of peptidoglycan modification in the antibody response to Staphylococcus aureus
探讨肽聚糖修饰在金黄色葡萄球菌抗体反应中的作用
- 批准号:
10549646 - 财政年份:2023
- 资助金额:
$ 10.17万 - 项目类别:
Identification of the antigenic targets of the clonal antibody response to Clostridioides difficile infection
鉴定针对艰难梭菌感染的克隆抗体反应的抗原靶点
- 批准号:
10742376 - 财政年份:2023
- 资助金额:
$ 10.17万 - 项目类别:
Genetic, structural and functional profiling of the human antibody response to arenavirus infection
人类抗体对沙粒病毒感染反应的遗传、结构和功能分析
- 批准号:
10688292 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别:
Molecular dissection of IgA antibody response by developing monoclonal IgA antibodies from nasal mucosa of mice
通过从小鼠鼻粘膜中开发单克隆 IgA 抗体对 IgA 抗体反应进行分子剖析
- 批准号:
22H02875 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein
绘制布氏锥虫变异表面糖蛋白的抗体反应
- 批准号:
10634694 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别:
Genetic, structural and functional profiling of the human antibody response to arenavirus infection
人类抗体对沙粒病毒感染反应的遗传、结构和功能分析
- 批准号:
10514498 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别:
Factors related to antibody response of COVID-19 vaccines: with focusing on metabolomics
与 COVID-19 疫苗抗体反应相关的因素:重点关注代谢组学
- 批准号:
22H03334 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mapping the antibody response to Trypanosoma brucei variant surface glycoprotein
绘制布氏锥虫变异表面糖蛋白的抗体反应
- 批准号:
10527979 - 财政年份:2022
- 资助金额:
$ 10.17万 - 项目类别: