Integrating human and non-human primate data to understand the acquisition of pre-erythrocytic immunity in the face of previous malaria exposure

整合人类和非人类灵长类动物数据,以了解在面对先前的疟疾暴露时获得红细胞前免疫力

基本信息

  • 批准号:
    10343399
  • 负责人:
  • 金额:
    $ 102.86万
  • 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:
    2022-02-10 至 2027-01-31
  • 项目状态:
    未结题

项目摘要

ABSTRACT Pre-erythrocytic (PE) malaria vaccines that completely prevent infection in malaria non-endemic regions have often failed to achieve equally high-level protection when tested in endemic regions. Data from animal models and humans has identified certain factors that may be contributing to this difference. Active or previous Plasmodium infections rank highly amongst these factors because infection is known to significantly impact innate and adaptive immune responses to malaria vaccines. We hypothesize that previous malaria exposure is a key driver of the suboptimal immunity observed in clinical trials of PE vaccines in endemic areas. However, a full assessment of how such conditions affect pre-erythrocytic immune responses is lacking in large part because much of the protective immune repertoire against PE malaria exists as tissue resident memory T cells in the liver, which is inaccessible in human clinical trials. Here, we propose to address this question of malaria vaccine hyporesponsiveness in endemic regions by performing vaccine studies in previously-infected versus naïve non-human primates (NHP) where we can study the tissue-specific response down to the single cell level and integrate these with data from peripheral blood samples from similarly-vaccinated human clinical trial participants in endemic and non-endemic regions. Our exhaustive studies in NHPs will be specifically guided by hypotheses derived directly from human data. The emerging high-density data will then be used to identify mechanisms, build models and formulate concrete hypotheses that can then be validated across a number of clinical trial samples with the overall goal of elucidating patterns or biomarkers that map with protection/lack of protection and immunogenicity/lack of immunogenicity in malaria-naïve and -experienced volunteers. Thus, we aim to: 1) define protective liver-resident PE immunity at the single cell level; 2) identify the mechanisms by which previous malaria exposure impacts baseline and innate immunity; 3) build models of the complex interplay between baseline, innate, and adaptive immunity and; 4) use these to identify strategies to overcome hyporesponsiveness to PE vaccines in endemic areas. This U01 project combines an inter-institutional, inter- disciplinary team of basic, translational, and clinical scientists from within and outside malaria whose unique expertise, resources, and collaborative style will create breakthroughs insights about this highly complex yet critically important vaccine challenge.
摘要

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)

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Sean C Murphy其他文献

Assessing the daily natural history of asymptomatic emPlasmodium/em infections in adults and older children in Katakwi, Uganda: a longitudinal cohort study
乌干达卡塔奎地区成年人和大龄儿童无症状疟原虫感染的每日自然史评估:一项纵向队列研究
  • DOI:
    10.1016/s2666-5247(23)00262-8
  • 发表时间:
    2024-01-01
  • 期刊:
  • 影响因子:
    20.400
  • 作者:
    Dianna E B Hergott;Tonny J Owalla;Weston J Staubus;Annette M Seilie;Chris Chavtur;Jennifer E Balkus;Bernadette Apio;Jimmy Lema;Barbara Cemeri;Andrew Akileng;Ming Chang;Thomas G Egwang;Sean C Murphy
  • 通讯作者:
    Sean C Murphy
Title: Implementing Selective Digestive Decontamination in the intensive care unit: A qualitative analysis of considerations identified by critical care nurses
标题:在重症监护病房实施选择性消化道净化:对重症监护护士确定的考虑因素进行定性分析
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    0
  • 作者:
    K. Kayentao;A. Ongoiba;Anne C Preston;Sara A. Healy;Zonghui Hu;Jeff Skinner;S. Doumbo;Jing Wang;H. Cisse;Didier Doumtabe;Abdrahamane Traoré;Hamadi Traore;Adama Djiguiba;Shanping Li;Mary E. Peterson;Shinyi Telscher;Azza H. Idris;William C Adams;Adrian B McDermott;S. Narpala;Bob C Lin;Leonid Serebryannyy;S. Hickman;Andrew J McDougal;Sandra Vazquez;Matthew Reiber;Judy A Stein;Jason G Gall;Kevin Carlton;P. Schwabl;Siriman Traore;Mamadou Keita;Amatigué Zéguimé;Adama Ouattara;M’Bouye Doucoure;Amagana Dolo;Sean C Murphy;D. E. Neafsey;S. Portugal;Abdoulaye A Djimde;B. Traore;Robert A. Seder;Peter D. Crompton
  • 通讯作者:
    Peter D. Crompton

Sean C Murphy的其他文献

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{{ truncateString('Sean C Murphy', 18)}}的其他基金

DDT-BMQ-0000100 Qualification of the Plasmodium falciparum 18S rRNA biomarker for malaria-endemic controlled human malaria infection studies
DDT-BMQ-0000100 疟疾流行控制人类疟疾感染研究中恶性疟原虫 18S rRNA 生物标志物的鉴定
  • 批准号:
    10836140
  • 财政年份:
    2023
  • 资助金额:
    $ 102.86万
  • 项目类别:
DDT-BMQ-0000107 Qualification of the Plasmodium falciparum 18S rRNA biomarker for malaria field studies
DDT-BMQ-0000107 用于疟疾现场研究的恶性疟原虫 18S rRNA 生物标志物的鉴定
  • 批准号:
    10616035
  • 财政年份:
    2022
  • 资助金额:
    $ 102.86万
  • 项目类别:
Integrating human and non-human primate data to understand the acquisition of pre-erythrocytic immunity in the face of previous malaria exposure
整合人类和非人类灵长类动物数据,以了解在面对先前的疟疾暴露时获得红细胞前免疫力
  • 批准号:
    10570273
  • 财政年份:
    2022
  • 资助金额:
    $ 102.86万
  • 项目类别:
Development of an oral liver-targeted prime-and-trap malaria vaccine
开发口服肝脏靶向引发和诱捕疟疾疫苗
  • 批准号:
    10533280
  • 财政年份:
    2020
  • 资助金额:
    $ 102.86万
  • 项目类别:
Development of an oral liver-targeted prime-and-trap malaria vaccine
开发口服肝脏靶向引发和诱捕疟疾疫苗
  • 批准号:
    10308679
  • 财政年份:
    2020
  • 资助金额:
    $ 102.86万
  • 项目类别:
Establishing the Feasibility of using daily Dried Blood Spots (DBS) to study the Natural History of Low-density Asymptomatic Malaria Infection to Inform Malaria Elimination
建立利用每日干血斑 (DBS) 研究低密度无症状疟疾感染自然史的可行性,为消除疟疾提供信息
  • 批准号:
    9974963
  • 财政年份:
    2020
  • 资助金额:
    $ 102.86万
  • 项目类别:
Establishing the Feasibility of using daily Dried Blood Spots (DBS) to study the Natural History of Low-density Asymptomatic Malaria Infection to Inform Malaria Elimination
建立利用每日干血斑 (DBS) 研究低密度无症状疟疾感染自然史的可行性,为消除疟疾提供信息
  • 批准号:
    10116276
  • 财政年份:
    2020
  • 资助金额:
    $ 102.86万
  • 项目类别:
Liver resident memory for malaria
疟疾的肝脏驻留记忆
  • 批准号:
    10054159
  • 财政年份:
    2018
  • 资助金额:
    $ 102.86万
  • 项目类别:
Liver resident memory for malaria
疟疾的肝脏驻留记忆
  • 批准号:
    10515643
  • 财政年份:
    2018
  • 资助金额:
    $ 102.86万
  • 项目类别:
Liver resident memory for malaria
疟疾的肝脏驻留记忆
  • 批准号:
    10542653
  • 财政年份:
    2018
  • 资助金额:
    $ 102.86万
  • 项目类别:

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