Developing a barcoded malaria parasite panel to assess broadly neutralizing antibodies
开发带条形码的疟原虫面板来评估广泛中和抗体
基本信息
- 批准号:10511052
- 负责人:
- 金额:$ 23.93万
- 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:2022-06-29 至 2024-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAllelesAntibodiesAntibody-mediated protectionAntigen TargetingAntigenic DiversityAntigenic VariationAntigensAntimalarialsAreaBar CodesBiologicalBiological AssayBloodCOVID-19 pandemicCRISPR/Cas technologyCellsChildClinicalDevelopmentDiseaseDrug ControlsEpitopesEquilibriumErythrocytesEvaluationExhibitsFalciparum MalariaFormulationGenetic PolymorphismGenetic RecombinationGenomicsGrowthHigh-Throughput Nucleotide SequencingHumanHumoral ImmunitiesImmune TargetingImmunizationImmunologicsIn VitroIndividualInfectionInsecticidesInvestmentsMalariaMalaria VaccinesMeasurementMeasuresMediatingMethodologyModificationMonoclonal AntibodiesNatural ImmunityParasite resistanceParasitesPathogenicityPathway interactionsPhenotypePlasmodium falciparumPopulationPublic HealthRecommendationResearchResistanceResourcesSamplingSpecificitySporozoitesTestingVaccine ResearchVaccinesVariantWorld Health Organizationbaseburden of illnesscombatcross immunityfunctional outcomesimmunogenicityinterestmalaria infectionneutralizing antibodyneutralizing vaccinenext generation sequencingnovel vaccinesparasite invasionpathogenpreventreverse geneticssuccesstoolvaccine developmentvector control
项目摘要
PROJECT SUMMARY
Malaria remains a grave threat to global public health with concern that the limited drugs and vector control
strategies at our disposal are becoming less effective. Recent progress and renewed interest in new vaccines
targeting pathogens, including the Plasmodium falciparum malaria parasite, provide an opportunity to expand
our toolkit to combat the disease. A highly efficacious vaccine for malaria, as for other eukaryotic parasites, has
been elusive. Substantial effort has been invested in development of a pre-erythrocytic vaccine targeting the
sporozoite form of the parasite, resulting in the recent recommendation by the World Health Organization for use
in endemic areas. During the clinical blood-stage of malaria, many of the functional antigens that provide the
parasite pathways for invasion into erythrocytes are known, and some naturally occurring antibodies are
protective. Antigenic diversity and variation, among other factors, poses a major challenge for a broadly-
neutralizing blood-stage vaccine, because many immune-targeted molecules for host cell entry are functionally
redundant and sequence polymorphic. As antigens continue to be tested for immunogenicity, it will become a
high-priority to identify those with the best potential for widespread protection against the breadth of antigenically
diverse malaria parasites found across the world. We propose here to develop a platform for facile assessment
of the broadly-neutralizing potential of anti-parasite antibodies. In Step 1, we will identify culture-adapted P.
falciparum clonal lines that represent all major alleles of the parasite globally; and implement state-of-the-art
CRISPR-Cas9 methodologies to introduce short, stably expressed barcode sequences to distinguish the lines.
In Step 2, we will pool 90 barcoded lines and validate the use of Illumina-based amplicon-sequencing to
deconvolute pools and measure the relative levels of the parasite lines. In Step 3, we will use the pooled assay
to measure the strain-specificity of invasion inhibition and broadly-neutralizing potential of monoclonal antibodies
targeting two antigens of interest for a blood-stage vaccine.
The combination of population genomics, reverse genetic modification of parasites, and quantitative high-
throughput sequencing, will permit us to analyze the functional outcomes of antigenic diversity at unprecedented
scale and complexity; and will transform efforts to identify the most promising antigens for a potent, broadly-
neutralizing malaria vaccine. We further anticipate that the approach will also be useful for non-vaccine related
studies for P. falciparum, including analysis of parasite resistance to antimalarials.
项目总结
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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Manoj T Duraisingh其他文献
Hungry for control: metabolite signaling to chromatin in emPlasmodium falciparum/em
渴望控制:恶性疟原虫中代谢物向染色质的信号传导
- DOI:
10.1016/j.mib.2024.102430 - 发表时间:
2024-04-01 - 期刊:
- 影响因子:7.500
- 作者:
Ruth Lappalainen;Manish Kumar;Manoj T Duraisingh - 通讯作者:
Manoj T Duraisingh
Manoj T Duraisingh的其他文献
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{{ truncateString('Manoj T Duraisingh', 18)}}的其他基金
Linking metabolite sensing and gene expression in malaria parasites
将疟疾寄生虫的代谢物传感和基因表达联系起来
- 批准号:
10593642 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Malaria parasite determinants of host cell tropism
疟疾寄生虫宿主细胞趋向性的决定因素
- 批准号:
10646370 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Evaluating host-directed therapeutics against blood-stage malaria parasites
评估针对血期疟疾寄生虫的宿主导向疗法
- 批准号:
10665779 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Evaluating host-directed therapeutics against blood-stage malaria parasites
评估针对血期疟疾寄生虫的宿主导向疗法
- 批准号:
10528133 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Malaria parasite determinants of host cell tropism
疟疾寄生虫宿主细胞趋向性的决定因素
- 批准号:
10522253 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Molecular basis of antimalarial drug resistance in Plasmodium vivax
间日疟原虫抗疟药物耐药性的分子基础
- 批准号:
10593992 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Developing a barcoded malaria parasite panel to assess broadly neutralizing antibodies
开发带条形码的疟原虫面板来评估广泛中和抗体
- 批准号:
10655645 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Comparative systems biology of apicomplexan cell division
顶端复合体细胞分裂的比较系统生物学
- 批准号:
10539938 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Comparative systems biology of apicomplexan cell division
顶端复合体细胞分裂的比较系统生物学
- 批准号:
10669790 - 财政年份:2022
- 资助金额:
$ 23.93万 - 项目类别:
Developing comparative chemical genomics and genetic validation tools for Babesia spp.
开发巴贝虫属的比较化学基因组学和遗传验证工具。
- 批准号:
10042448 - 财政年份:2020
- 资助金额:
$ 23.93万 - 项目类别:
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