Impact of prior influenza exposures on antibody repertoires to new viral strains
先前流感暴露对新病毒株抗体库的影响
基本信息
- 批准号:9977954
- 负责人:
- 金额:$ 41.85万
- 依托单位:
- 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:2014-08-15 至 2023-07-31
- 项目状态:已结题
- 来源:
- 关键词:3 year oldAffectAnimal ModelAnimalsAntibodiesAntibody RepertoireAntibody ResponseAntibody SpecificityAntibody titer measurementBiological AssayBirthChildChildhoodCohort StudiesDevelopmentDistantEffectivenessEnrollmentEpitopesFerretsFundingGoalsGrantHumanImmuneImmune responseImmune systemImmunityImmunologicsIndividualInfectionInfluenzaInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H2N2 SubtypeInfluenza A Virus, H3N2 SubtypeInfluenza A Virus, H5N1 SubtypeInfluenza A Virus, H7N9 SubtypeInfluenza vaccinationLifeLongitudinal StudiesMemory B-LymphocyteModelingNicaraguanPediatric cohortPredispositionPropertyRecording of previous eventsSamplingSeriesSerologicalShapesSpecificityTestingTimeVaccinatedVaccine AntigenVaccinesViralVirusVirus Diseasesbasecohortearly childhoodepidemiology studyimprintinfluenza virus straininfluenza virus vaccineinfluenzavirusinterestpandemic diseasepandemic influenzaresponseseasonal influenzauniversal influenza vaccineuniversal vaccinevaccine candidate
项目摘要
Most humans are infected with influenza viruses by the time they reach 3 years of age. Our past studies
suggest that early childhood influenza infections can leave lifelong immunological `imprints'. During the first
funding period (4 years) of this grant, we found that human Ab responses against seasonal influenza viruses
are typically focused on epitopes that are conserved between contemporary viral strains and viral strains that
circulated during each individual donor's childhood. We found that immune responses generated against
contemporary influenza strains are dominated by memory B cells that recognize conserved epitopes present in
past viral strains. Our studies have examined how viral infections with one subtype of influenza virus (i.e.
H1N1) influence immune responses against an antigenically distinct version of that same subtype (i.e. H1N1).
Although different influenza virus subtypes have very different antigenic properties, there are epitopes that are
conserved among these viruses. H1N1, H2N2, and H3N2 viruses have circulated at different times in humans
over the past 100 years and an individual's birth year largely predicts the influenza virus subtype that they were
initially infected with in childhood. It is important to elucidate how viral infections with one influenza subtype
(i.e. H1N1) influence immune responses against a completely different influenza subtype (i.e. H3N2) since
multiple influenza virus subtypes currently co-circulate in humans. Further, epidemiological studies suggest
that human susceptibility to pandemic H5N1 and H7N9 viruses is influenced by childhood infections with
different subtypes of seasonal influenza viruses. We hypothesize that early childhood seasonal influenza virus
infections leave long-lived immunological imprints that bias the immune system to preferentially respond
efficiently to more closely related influenza subtypes and poorly to more distant influenza subtypes. In this
proposal we will use a ferret model to determine how initial seasonal influenza infections shape the specificity
and neutralization efficiency of Abs elicited against distinct seasonal and pandemic influenza virus subtypes.
We will then examine sera samples collected for a pediatric cohort study to determine how initial childhood
H1N1 versus H3N2 infections affect the development of Ab responses against infections with homologous and
heterologous influenza virus subtypes. Finally, we will use a ferret model to determine how different influenza
pre-exposures shape the specificity and neutralization efficiency of Abs elicited by a leading `universal'
influenza vaccine candidate. Collectively, these studies will determine (1) if infections with one influenza virus
subtype influence the specificity of Abs elicited against a second influenza virus subtype, (2) the specificity and
functionality of Abs elicited in children with different influenza virus exposure histories and (3) how prior
influenza exposures influence the effectiveness of a new `universal' influenza vaccine.
大多数人在3岁时感染流感病毒。我们过去的研究
这表明,儿童早期流感感染可留下终生免疫"印记"。在第一
在该基金资助期(4年)内,我们发现人类抗体对季节性流感病毒的反应
典型地集中于在当代病毒株和
在每个捐赠者的童年时期流传。我们发现免疫系统产生的免疫反应
当代流感病毒株由记忆B细胞支配,记忆B细胞识别存在于
过去的病毒株。我们的研究已经检查了一种流感病毒亚型(即,
H1N1)影响针对同一亚型(即H1N1)抗原性不同版本的免疫应答。
尽管不同的流感病毒亚型具有非常不同的抗原特性,但存在与流感病毒亚型相同的表位。
在这些病毒中是保守的H1N1、H2N2和H3N2病毒在不同时期在人类中传播
在过去的100年里,一个人的出生年份在很大程度上预测了他们所患的流感病毒亚型。
最初是在儿童时期感染的。重要的是要阐明一种流感亚型的病毒感染
(i.e. H1N1)影响针对完全不同的流感亚型(即H3N2)的免疫应答,
多种流感病毒亚型目前在人类中共同传播。此外,流行病学研究表明,
人类对大流行性H5N1和H7N9病毒的易感性受到儿童感染的影响,
不同亚型的季节性流感病毒。我们假设儿童早期季节性流感病毒
感染会留下持久的免疫印记,使免疫系统倾向于优先做出反应,
对更密切相关的流感亚型有效,而对更远的流感亚型效果不佳。在这
建议我们将使用雪貂模型来确定初始季节性流感感染如何影响特异性
和针对不同的季节性和大流行性流感病毒亚型引发的Ab的中和效率。
然后,我们将检查为儿科队列研究收集的血清样本,以确定最初的儿童期
H1N1与H3N2感染影响针对同源和非同源病毒感染的抗体应答的发展,
异源流感病毒亚型。最后,我们将使用雪貂模型来确定不同的流感
预暴露塑造了由一种领先的"通用"抗体引起的抗体的特异性和中和效率。
流感疫苗候选人。总的来说,这些研究将确定(1)是否感染一种流感病毒
亚型影响针对第二流感病毒亚型引发的Ab的特异性,(2)特异性和
在具有不同流感病毒暴露史的儿童中引起的Ab的功能性和(3)先前如何
流感暴露影响新的"通用"流感疫苗的有效性。
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 }}
Scott Eric Hensley其他文献
Scott Eric Hensley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('Scott Eric Hensley', 18)}}的其他基金
Establishing ferret models to optimize new influenza vaccines that replace original antigenic sin with initial blessings of induced immunity
建立雪貂模型以优化新型流感疫苗,以诱导免疫的初步祝福取代原有的抗原原罪
- 批准号:
10202186 - 财政年份:2020
- 资助金额:
$ 41.85万 - 项目类别:
Impact of prior influenza exposures on antibody repertoires to new viral strains
先前流感暴露对新病毒株抗体库的影响
- 批准号:
9339804 - 财政年份:2016
- 资助金额:
$ 41.85万 - 项目类别:
Impact of prior influenza exposures on antibody repertoires to new viral strains
先前流感暴露对新病毒株抗体库的影响
- 批准号:
9306754 - 财政年份:2016
- 资助金额:
$ 41.85万 - 项目类别:
The effect of human pre-exposure history on antigenic drift of influenza viruses
人类暴露前史对流感病毒抗原漂移的影响
- 批准号:
9332001 - 财政年份:2016
- 资助金额:
$ 41.85万 - 项目类别:
Impact of prior influenza exposures on antibody repertoires to new viral strains
先前流感暴露对新病毒株抗体库的影响
- 批准号:
10451839 - 财政年份:2014
- 资助金额:
$ 41.85万 - 项目类别:
The effect of human pre-exposure history on antigenic drift of influenza viruses
人类暴露前史对流感病毒抗原漂移的影响
- 批准号:
9060857 - 财政年份:2014
- 资助金额:
$ 41.85万 - 项目类别:
The effect of human pre-exposure history on antigenic drift of influenza viruses
人类暴露前史对流感病毒抗原漂移的影响
- 批准号:
8756454 - 财政年份:2014
- 资助金额:
$ 41.85万 - 项目类别:
Elucidation of mechanisms that contribute to antigenic drift of influenza viruses
阐明导致流感病毒抗原漂移的机制
- 批准号:
8099226 - 财政年份:2011
- 资助金额:
$ 41.85万 - 项目类别:
Elucidation of mechanisms that contribute to antigenic drift of influenza viruses
阐明导致流感病毒抗原漂移的机制
- 批准号:
8255436 - 财政年份:2011
- 资助金额:
$ 41.85万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 41.85万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 41.85万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 41.85万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 41.85万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 41.85万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 41.85万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 41.85万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 41.85万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 41.85万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 41.85万 - 项目类别:
Studentship