Defining targets of protective immunity to vivax malaria using human monoclonal antibodies
使用人单克隆抗体确定间日疟疾的保护性免疫目标
基本信息
- 批准号:10353401
- 负责人:
- 金额:$ 70.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-24 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AddressAdjuvantAdultAffinityAfrica South of the SaharaAmino Acid SequenceAntibodiesAntigensAreaB-LymphocytesBinding ProteinsBiological AssayBiomassBloodBrazilCambodiaCellsCessation of lifeChildChimeric ProteinsChronicClinicalClone CellsComplementCopy Number PolymorphismDataDevelopmentDrug resistanceEpitopesErythrocytesEthiopiaEventExposure toFeverGene DosageGenetic PolymorphismGeographyGoalsHealth PolicyHepaticHepatocyteHumanImmuneImmune SeraImmunityImmunizeImmunoglobulin GImmunologistIn VitroIndividualInfectionInfection preventionInjectionsKnowledgeLiverLongitudinal cohortLymphocyteMalariaMalaria VaccinesMeasuresMediatingMonoclonal AntibodiesMorbidity - disease ratePapua New GuineaParasitesPatientsPersonsPlasmodium falciparumPlasmodium vivaxPlasmodium vivax vaccinePlayPopulationPopulation HeterogeneityPreventionPrevention approachPrimary InfectionProductionProteinsPublic HealthRelapseResidual stateReticulocytesRiskRoleSolomon IslandsSporozoitesSyndromeTechnologyTimeTranscendTransgenic OrganismsVaccinesVivax MalariaWorkapical membranecircumsporozoite proteindesigndisorder riskexperimental studyhuman monoclonal antibodiesin vitro Assayin vivoinnovationmigrationmouse modelneutralizing monoclonal antibodiesnext generationnovel strategiesnovel therapeuticsnovel vaccinesparasite invasionpreventrational designreceptorreceptor bindingsample fixationtransmission processvaccine developmentvaccine strategyvaccine-induced immunity
项目摘要
The goal of our proposal is to develop new approaches for the prevention and treatment of human malaria
caused by the parasite Plasmodium vivax (P. vivax). This type of malaria, known as vivax malaria, is the most
widely distributed type of malaria with 3.3 billion people at risk and at least 15 million clinical cases worldwide
each year. As the most common form of malaria outside sub-Saharan Africa, it can cause severe illness and
death across a large segment of the world's population. Most individuals exposed to P. vivax through repeated
infection gain partial immunity over time. The immunity is mediated, in part, by acquired antibodies (Abs) to
essential parasite proteins that can block the parasite invasion into liver and red blood cells thereby preventing
infection and if infected reduce the risk of disease. This proposal aims to isolate human monoclonal antibodies
(mAbs) from individuals with immunity to vivax malaria that recognize a few key molecules known to be
essential for invasion of liver and red blood cells. Once isolated these mAbs will be evaluated as to whether
they block parasite invasion of liver and red cells in vitro, and in vivo using murine models and genetically
modified parasites. Monoclonal Abs with potent blocking activity will be further characterized as to exactly how
and where they interact with parasite proteins and whether individuals in diverse populations also have the
same or similar antibodies. This information can be used to help to design a vaccine against vivax malaria.
These mAbs can also be used for treatment of severely ill patients, or for prevention of vivax malaria over time,
since a single injection of modified mAbs can last for weeks and even months.
我们建议的目标是开发预防和治疗人类疟疾的新方法。
由间日疟原虫(P.vivax)引起。这种类型的疟疾,被称为间日疟疾,是最
分布广泛的疟疾类型,全球有33亿人面临风险,至少有1500万临床病例
每年。作为撒哈拉以南非洲以外最常见的疟疾形式,它可以导致严重的疾病和
世界上很大一部分人口死亡。大多数人通过反复接触间日疟原虫
随着时间的推移,感染会获得部分免疫力。这种免疫在一定程度上是由获得性抗体(Abs)介导的
基本的寄生虫蛋白质,可以阻止寄生虫入侵肝脏和红细胞,从而防止
感染,如果被感染,则降低疾病风险。这项提议旨在分离人的单抗。
(单抗)来自对间日疟有免疫力的人,识别一些已知的关键分子
对肝脏和红细胞的入侵是必不可少的。一旦分离,这些单抗将被评估是否
它们在体外和体内用小鼠模型和遗传学方法阻止寄生虫对肝脏和红细胞的入侵
修改过的寄生虫。具有强大封闭活性的单抗将进一步表征到底是如何
以及它们与寄生虫蛋白的相互作用,以及不同种群中的个体是否也有
相同或相似的抗体。这些信息可以用来帮助设计针对间日疟的疫苗。
这些单抗还可用于治疗重病患者,或随着时间的推移预防间日疟,
因为单次注射修饰的单抗可持续数周甚至数月。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Christopher L King其他文献
Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents
在疗养院居民中接种 XBB.1.5 疫苗对先前的 SARS-CoV-2 毒株和 JN.1 变异体具有广泛的免疫原性
- DOI:
10.1101/2024.03.21.24303684 - 发表时间:
2024 - 期刊:
- 影响因子:0
- 作者:
Yasin Abul;Clare Nugent;Igor Vishnepolskiy;Tiffany Wallace;Evan Dickerson;Laurel Holland;Iva Esparza;Mandi Winkis;Kazi Tanvee Wali;Philip A Chan;Rosa R. Baier;Amy Recker;Matthew Kaczynski;Shreya Kamojjala;Alexander Pralea;Hailee Rice;Olubunmi Osias;Oladayo A. Oyebanji;Olajide J. Olagunju;Yi Cao;Chia Jung Li;Alex Roederer;Walther M. Pfeifer;Christopher L King;J. Bosch;Aman Nanda;Lynn McNicoll;Nadia Mujahid;S. Raza;Rohit Tyagi;Brigid M Wilson;Elizabeth M. White;David H Canaday;Stefan Gravenstein;A. Balazs - 通讯作者:
A. Balazs
Evaluating PK/PD Relationship of CNS Drug by Using Liquid Chromtography/ Tandem Mass Spectrometry Coupled to In Vivo Microdialysis
使用液相色谱/串联质谱联用体内微透析评估中枢神经系统药物的 PK/PD 关系
- DOI:
10.5772/33100 - 发表时间:
2012 - 期刊:
- 影响因子:0
- 作者:
Y. Qu;L. Olson;X. Jiang;L. Aluisio;Christopher L King;E. Jones;T. Lovenberg - 通讯作者:
T. Lovenberg
Christopher L King的其他文献
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{{ truncateString('Christopher L King', 18)}}的其他基金
Defining targets of protective immunity to vivax malaria using human monoclonal antibodies
使用人单克隆抗体确定间日疟疾的保护性免疫目标
- 批准号:
10132239 - 财政年份:2020
- 资助金额:
$ 70.67万 - 项目类别:
Defining targets of protective immunity to vivax malaria using human monoclonal antibodies
使用人单克隆抗体确定间日疟疾的保护性免疫目标
- 批准号:
10599119 - 财政年份:2020
- 资助金额:
$ 70.67万 - 项目类别:
Early Drivers of Humoral Immunity to SARS-CoV-2 Infections
SARS-CoV-2 感染体液免疫的早期驱动因素
- 批准号:
10222232 - 财政年份:2020
- 资助金额:
$ 70.67万 - 项目类别:
Early Drivers of Humoral Immunity to SARS-CoV-2 Infections
SARS-CoV-2 感染体液免疫的早期驱动因素
- 批准号:
10680626 - 财政年份:2020
- 资助金额:
$ 70.67万 - 项目类别:
Defining targets of protective immunity to vivax malaria using human monoclonal antibodies
使用人单克隆抗体确定间日疟疾的保护性免疫目标
- 批准号:
9973847 - 财政年份:2020
- 资助金额:
$ 70.67万 - 项目类别:
Early Drivers of Humoral Immunity to SARS-CoV-2 Infections
SARS-CoV-2 感染体液免疫的早期驱动因素
- 批准号:
10855050 - 财政年份:2020
- 资助金额:
$ 70.67万 - 项目类别:
Defining targets of protective immunity in Plasmodium vivax using human monoclonal antibodies
使用人单克隆抗体确定间日疟原虫保护性免疫的目标
- 批准号:
10651591 - 财政年份:2014
- 资助金额:
$ 70.67万 - 项目类别:
Strain-specific Immunity to Plasmodium vivax malaria
对间日疟原虫疟疾的菌株特异性免疫
- 批准号:
8542980 - 财政年份:2014
- 资助金额:
$ 70.67万 - 项目类别:
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