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:
    10451839
  • 负责人:
  • 金额:
    $ 39.86万
  • 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 2024-07-31
  • 项目状态:
    已结题

项目摘要

Modified Project Summary/Abstract Section 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 mouse and ferret models 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 mouse and ferret models 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.
修改项目摘要/摘要部分 大多数人在3岁时感染流感病毒。 我们过去的研究表明,儿童早期流感感染可能会留下终身的免疫“印记”。 在该资助的第一个资助期(4年),我们发现人类对季节性流感病毒的抗体反应通常集中在当代病毒株和每个捐赠者童年时期传播的病毒株之间保守的表位上。 我们发现,针对当代流感病毒株产生的免疫应答由记忆B细胞主导,记忆B细胞识别过去病毒株中存在的保守表位。 我们的研究已经检查了一种流感病毒亚型(即H1N1)的病毒感染如何影响针对同一亚型(即H1N1)的抗原性不同版本的免疫应答。 虽然不同的流感病毒亚型具有非常不同的抗原特性,但这些病毒之间存在保守的表位。 在过去的100年里,H1N1、H2 N2和H3 N2病毒在不同的时间在人类中传播,一个人的出生年份在很大程度上可以预测他们在童年时最初感染的流感病毒亚型。重要的是要阐明一种流感亚型(即H1N1)的病毒感染如何影响针对完全不同的流感亚型(即H3 N2)的免疫应答,因为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H5 N1和H7N9病毒的易感性受到儿童感染不同亚型季节性流感病毒的影响。 我们假设,早期儿童季节性流感病毒感染会留下长期的免疫印记,使免疫系统优先有效地对更密切相关的流感亚型做出反应,而对更遥远的流感亚型做出反应。 在本提案中,我们将使用小鼠和雪貂模型来确定初始季节性流感感染如何影响针对不同季节性和大流行性流感病毒亚型的抗体的特异性和中和效率。 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H1N1与H3 N2感染如何影响同源和异源流感病毒亚型感染的抗体反应的发展。 最后,我们将使用小鼠和雪貂模型来确定不同的流感预暴露如何塑造由领先的“通用”流感候选疫苗引起的抗体的特异性和中和效率。 总的来说,这些研究将确定(1)一种流感病毒亚型的感染是否影响针对第二种流感病毒亚型的抗体的特异性,(2)在具有不同流感病毒暴露史的儿童中引发的抗体的特异性和功能性,以及(3)既往流感暴露如何影响新的“通用”流感疫苗的有效性。

项目成果

期刊论文数量(21)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Development of a nucleoside-modified mRNA vaccine against clade 2.3.4.4b H5 highly pathogenic avian influenza virus.
开发针对进化枝 2.3.4.4b H5 高致病性禽流感病毒的核苷修饰 mRNA 疫苗。
  • DOI:
    10.1101/2023.04.30.538854
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Furey,Colleen;Ye,Naiqing;Kercher,Lisa;DeBeauchamp,Jennifer;Crumpton,JeriCarol;Jeevan,Trushar;Patton,Christopher;Franks,John;Alameh,Mohamad-Gabriel;Fan,StevenHY;Phan,AnthonyT;Hunter,ChristopherA;Webby,RichardJ;Weissman,Drew
  • 通讯作者:
    Weissman,Drew
Propagation and Characterization of Influenza Virus Stocks That Lack High Levels of Defective Viral Genomes and Hemagglutinin Mutations.
  • DOI:
    10.3389/fmicb.2016.00326
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    5.2
  • 作者:
    Xue J;Chambers BS;Hensley SE;López CB
  • 通讯作者:
    López CB
Antibodies Against the Current Influenza A(H1N1) Vaccine Strain Do Not Protect Some Individuals From Infection With Contemporary Circulating Influenza A(H1N1) Virus Strains.
  • DOI:
    10.1093/infdis/jiw479
  • 发表时间:
    2016-12-15
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Petrie JG;Parkhouse K;Ohmit SE;Malosh RE;Monto AS;Hensley SE
  • 通讯作者:
    Hensley SE
Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012-2013.
Antibodies with 'Original Antigenic Sin' Properties Are Valuable Components of Secondary Immune Responses to Influenza Viruses.
  • DOI:
    10.1371/journal.ppat.1005806
  • 发表时间:
    2016-08
  • 期刊:
  • 影响因子:
    6.7
  • 作者:
    Linderman SL;Hensley SE
  • 通讯作者:
    Hensley SE
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Scott Eric Hensley其他文献

Scott Eric Hensley的其他文献

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{{ 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:
    $ 39.86万
  • 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:
    $ 39.86万
  • 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:
    $ 39.86万
  • 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:
    $ 39.86万
  • 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:
    $ 39.86万
  • 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:
    9977954
  • 财政年份:
    2014
  • 资助金额:
    $ 39.86万
  • 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:
    $ 39.86万
  • 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:
    $ 39.86万
  • 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:
    $ 39.86万
  • 项目类别:
Core C: Humoral and Serological Core
核心 C:体液和血清学核心
  • 批准号:
    10180873
  • 财政年份:
    2009
  • 资助金额:
    $ 39.86万
  • 项目类别:

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