Immuno-epidemiological epitope mapping of a blood stage malaria vaccine antigen

血期疟疾疫苗抗原的免疫流行病学表位作图

基本信息

  • 批准号:
    8234592
  • 负责人:
  • 金额:
    $ 58.98万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-02-02 至 2016-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): An effective blood stage Plasmodium falciparum malaria vaccine would be of immense global health benefit, particularly for infants and young children who suffer the greatest burden of malaria morbidity and mortality. We propose to use novel molecular epidemiological and structural vaccinology approaches to understand the human immune response to and the resulting antigenic diversity of apical membrane antigen-1 (AMA1), a leading malaria vaccine candidate antigen. AMA1 is highly polymorphic; antigenic variation is likely a parasite immune escape mechanism that allows repeated infection with different variants in the face of natural immunity. We recently completed the first Phase 2 clinical trial of a monovalent AMA1- based malaria vaccine in children in Mali, West Africa. The vaccine had limited overall efficacy but good allele-specific efficacy against clinical malaria caused by parasites with AMA1 homologous to the vaccine strain with respect to immunologically relevant polymorphisms in AMA1. Molecular epidemiological and animal studies suggest that some regions of the AMA1 molecule represent "immunogenicity hot spots," i.e. residues within these regions are critical to development of strain-specific protective immunity. The combined results of these clinical and laboratory studies suggest that the vast diversity of AMA1 alleles may be consolidated into a smaller number of subgroups, thereby reducing the number of variants that would have to be included to achieve a broadly cross-protective AMA1 vaccine. The proposed translational research project will employ novel molecular epidemiological approaches that we have developed, as well as a novel autotransporter protein expression system, to analyze patient serum samples collected in prospective longitudinal studies in a malaria endemic area, with the aim of identifying cross-reactive and cross-protective AMA1 epitopes. PUBLIC HEALTH RELEVANCE: One reason there is still no malaria vaccine is because malaria parasites are able to mutate and change to escape natural immunity. This project seeks to understand how the human immune system interacts with rapidly changing malaria parasites to provide natural protection against malaria infection in the field. This information will be used to better understand how to make a vaccine that could protect against the many diverse forms of malaria parasites found in nature.
描述(由申请人提供):有效的血期恶性疟原虫疟疾疫苗将对全球健康产生巨大益处,特别是对疟疾发病率和死亡率负担最重的婴儿和幼儿。我们建议使用新的分子流行病学和结构疫苗学方法来了解人类对一种主要的疟疾疫苗候选抗原——顶膜抗原-1 (apical membrane antigen-1, AMA1)的免疫反应和由此产生的抗原多样性。AMA1是高度多态性的;抗原变异可能是一种寄生虫免疫逃逸机制,在面对自然免疫时允许不同变异的重复感染。我们最近在西非马里的儿童中完成了单价基于AMA1的疟疾疫苗的第一期2期临床试验。从AMA1的免疫学相关多态性来看,该疫苗对具有与疫苗菌株同源的AMA1的寄生虫引起的临床疟疾具有有限的总体效力,但具有良好的等位基因特异性效力。分子流行病学和动物研究表明,AMA1分子的某些区域代表“免疫原性热点”,即这些区域内的残基对菌株特异性保护性免疫的发展至关重要。这些临床和实验室研究的综合结果表明,AMA1等位基因的巨大多样性可能被整合为较小数量的亚群,从而减少了为实现广泛交叉保护的AMA1疫苗而必须包括的变异数量。该转化研究项目将采用我们开发的新型分子流行病学方法,以及一种新的自转运蛋白表达系统,分析在疟疾流行地区的前瞻性纵向研究中收集的患者血清样本,目的是识别交叉反应和交叉保护的AMA1表位。

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 V. PLOWE其他文献

CHRISTOPHER V. PLOWE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 V. PLOWE', 18)}}的其他基金

Ultra-dense peptide array analysis of naturally acquired and vaccine-induced P. falciparum immunity
自然获得性和疫苗诱导的恶性疟原虫免疫的超密集肽阵列分析
  • 批准号:
    9182505
  • 财政年份:
    2016
  • 资助金额:
    $ 58.98万
  • 项目类别:
Safety and efficacy of PfSPZ malaria vaccine in malaria-exposed adults
PfSPZ 疟疾疫苗对疟疾暴露成人的安全性和有效性
  • 批准号:
    8989966
  • 财政年份:
    2015
  • 资助金额:
    $ 58.98万
  • 项目类别:
Pilot studies of the molecular epidemiology of drug-resistant malaria in Myanmar
缅甸耐药疟疾分子流行病学试点研究
  • 批准号:
    8583301
  • 财政年份:
    2012
  • 资助金额:
    $ 58.98万
  • 项目类别:
Immuno-epidemiological epitope mapping of a blood stage malaria vaccine antigen
血期疟疾疫苗抗原的免疫流行病学表位作图
  • 批准号:
    8607885
  • 财政年份:
    2012
  • 资助金额:
    $ 58.98万
  • 项目类别:
Pilot studies of the molecular epidemiology of drug-resistant malaria in Myanmar
缅甸耐药疟疾分子流行病学试点研究
  • 批准号:
    8356232
  • 财政年份:
    2012
  • 资助金额:
    $ 58.98万
  • 项目类别:
Immuno-epidemiological epitope mapping of a blood stage malaria vaccine antigen
血期疟疾疫苗抗原的免疫流行病学表位作图
  • 批准号:
    8795656
  • 财政年份:
    2012
  • 资助金额:
    $ 58.98万
  • 项目类别:
Immuno-epidemiological epitope mapping of a blood stage malaria vaccine antigen
血期疟疾疫苗抗原的免疫流行病学表位作图
  • 批准号:
    8416955
  • 财政年份:
    2012
  • 资助金额:
    $ 58.98万
  • 项目类别:
Randomized, controlled trial of daily trimethoprim-sulfamethoxazole or weekly chl
每日甲氧苄啶-磺胺甲恶唑或每周一次 Chl 的随机对照试验
  • 批准号:
    7511837
  • 财政年份:
    2008
  • 资助金额:
    $ 58.98万
  • 项目类别:
Malaria Vaccine Trials in Mali
马里的疟疾疫苗试验
  • 批准号:
    6960293
  • 财政年份:
    2005
  • 资助金额:
    $ 58.98万
  • 项目类别:
Genetic diversity and protective immunity to malaria infection and disease
遗传多样性和对疟疾感染和疾病的保护性免疫力
  • 批准号:
    8291906
  • 财政年份:
    2005
  • 资助金额:
    $ 58.98万
  • 项目类别:

相似海外基金

Multi-component interventions to reducing unhealthy diets and physical inactivity among adolescents and youth in sub-Saharan Africa (Generation H)
采取多方干预措施减少撒哈拉以南非洲青少年的不健康饮食和缺乏身体活动(H 代)
  • 批准号:
    10106976
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    EU-Funded
Exploring the mental health and wellbeing of adolescent parent families affected by HIV in South Africa
探讨南非受艾滋病毒影响的青少年父母家庭的心理健康和福祉
  • 批准号:
    ES/Y00860X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Fellowship
Decolonization, Appropriation and the Materials of Literature in Africa and its Diaspora
非洲及其侨民的非殖民化、挪用和文学材料
  • 批准号:
    EP/Y024516/1
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Research Grant
Exploring "Actionable Information" for Learning Improvement in Rural East Africa: A Positive Deviance Approach
探索东非农村地区学习改进的“可行信息”:积极偏差方法
  • 批准号:
    24K00390
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Water stressed cities: individual choice, access to water and pathways to resilience in sub-Saharan Africa
缺水城市:撒哈拉以南非洲地区的个人选择、水资源获取和恢复力途径
  • 批准号:
    MR/X022943/1
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Fellowship
Protecting Women from Economic shocks to fight HIV in Africa (POWER)
保护非洲妇女免受经济冲击,抗击艾滋病毒 (POWER)
  • 批准号:
    MR/Y003837/1
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Fellowship
Tackling antimicrobial resistance across dentistry in Sub-Saharan Africa.
解决撒哈拉以南非洲牙科领域的抗菌素耐药性问题。
  • 批准号:
    MR/Y019695/1
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Research Grant
ePowerCart - Affordable Mobile Clean Energy for Remote Communities in Rural Sub-Saharan Africa and India
ePowerCart - 为撒哈拉以南非洲和印度农村偏远社区提供经济实惠的移动清洁能源
  • 批准号:
    10076185
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Collaborative R&D
Co-designing effective Nature-based Solutions in coastal West Africa
在西非沿海共同设计有效的基于自然的解决方案
  • 批准号:
    NE/Z503460/1
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Research Grant
NIGHTCOOL: Deployment of FREECOOL+ for night cooling strategies in Africa
NIGHTCOOL:部署 FREECOOL 以实施非洲夜间制冷策略
  • 批准号:
    10105520
  • 财政年份:
    2024
  • 资助金额:
    $ 58.98万
  • 项目类别:
    Demonstrator
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了