Chimeric hybrid transmission blocking vaccine for malaria
疟疾嵌合混合传播阻断疫苗
基本信息
- 批准号:8424202
- 负责人:
- 金额:$ 22万
- 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:2012-02-15 至 2016-01-31
- 项目状态:已结题
- 来源:
- 关键词:Active ImmunizationAdjuvantAdverse eventAdverse reactionsAfricaAmericasAnopheles GenusAntibodiesAntibody AffinityAntibody FormationAntigen PresentationAntigensApplications GrantsAreaAttentionBiological AssayBlocking AntibodiesCD4 Positive T LymphocytesCarrier ProteinsCategoriesChemicalsChimeric ProteinsClinicalClinical TrialsClinical Trials DesignCodon NucleotidesConjugate VaccinesCulicidaeDataDevelopmentDrug FormulationsDrug resistanceEmulsionsEpidermal Growth FactorEpitopesErythrocytesEscherichia coliFertilizationFutureGeneticGeographic DistributionGlycine decarboxylaseGoalsHealthHelper-Inducer T-LymphocyteHumanHybridsImmune responseImmune systemImmunityImmunizationIn VitroInfectionInfection ControlLeadLongevityMacaca mulattaMalariaMalaria VaccinesMeasuresMembraneMerozoite Surface Protein 1MethodologyMidgutModelingMolecular ConformationMonitorMontanide ISA-51MusNatureOilsParasitesPassive ImmunizationPhasePlasmodiumPlasmodium falciparumPlasmodium vivaxProtein FragmentProteinsPublishingReagentRecombinant ProteinsRecombinantsRegimenReportingResearchResearch ProposalsResourcesRiskSafetySexual DevelopmentSoutheastern AsiaStagingStructureSurfaceSynthetic GenesSystemT-LymphocyteT-Lymphocyte EpitopesTestingTherapeuticTimeTransgenic OrganismsTrefoil MotifVaccinesVivax MalariaWaterYeastsacquired immunitybasecomparativefeedingfertilization antigengenetic linkagehybrid geneimmunogenicimmunogenicityimprovedin vitro Assayin vivoinnovationnovelpreventprogramsprophylacticresearch studyresistant straintooltransmission processvaccine candidatevaccine evaluationvectorzygote
项目摘要
DESCRIPTION (provided by applicant): The overall goal of this R21 research proposal is to develop and evaluate the potential of a novel chimeric construct based on Pvs25 as an effective Plasmodium vivax transmission blocking vaccine (TBV). Given the emergence and spread of drug-resistant parasites, and the global malaria eradication agenda, the development of novel tools to control malaria transmission is an essential priority. Plasmodium vivax is the most prevalent of the human malaria parasites outside Africa with an estimated 80% of the cases in South and Southeast Asia and 70% in the Americas. Although Pvs25 vaccine constructs have reached a phase of clinical development, a main concern in the field is its poor immunogenicity. Strategies used to date to enhance the immunogenicity include changes in the delivery system and formulation. However, a clinical trial using a water- in-oil emulsion was halted due to severe systemic adverse events. New methodologies to improve safety and immunogenicity of Pvs25 are required. We have recently shown that the homospecific CD4+ help, provided by the genetic linkage of tandem Plasmodium promiscuous T cell epitopes to a merozoite vaccine candidate, improves efficacy by a direct effect on the quality of the antibody response. We hypothesized that this T helper module (HM) can be used as a carrier molecule to enhance the immunogenicity of Pvs25 and induce a robust transmission blocking immunity. We have genetically fused the synthetic gene encoding HM into a codon optimized synthetic gene encoding Pvs25. The hybrid gene has been successfully expressed in E. coli in a properly folded conformation. The studies proposed aim to (1) test in comparative experiments in mice the effect of a HM on Pvs25 immunogenicity and (2) assess the safety and immunogenicity of the novel chimeric construct in rhesus macaques. Transmission blocking immunity will be tested in vivo using a P. berghei transgenic parasite expressing Pvs25 and in vitro using standard membrane-feeding assays. These studies have the general goal of showing that a HM can be used as a carrier platform for poorly immunogenic malaria antigens. Given the dramatic impact of malaria with increasing attention on the widespread and severe nature of P. vivax, and the urgent need for novel control measures to reduce transmission, our proposal has the potential to serve as the framework for future development of effective multi-stage vaccines.
描述(由申请人提供):该R21研究建议的总体目标是开发和评估基于PVS25的新型嵌合构建体的潜力,作为一种有效的疟原虫元素传输阻断疫苗(TBV)。鉴于耐药寄生虫的出现和传播以及全球消除疟疾的议程,控制疟疾传播的新工具的开发是必不可少的。疟原虫是非洲以外的人类疟疾中最普遍的疟原虫,估计有80%的南亚和东南亚病例,在美洲70%。尽管PVS25疫苗构建体已经达到了临床发育的阶段,但该领域的主要问题是其免疫原性。迄今为止,用于增强免疫原性的策略包括输送系统和配方的变化。但是,由于严重的全身不良事件,使用水上乳液的临床试验停止了。需要新的方法来提高PVS25的安全性和免疫原性。我们最近表明,由串联质质子杂化T细胞表位与梅罗唑群疫苗候选者的遗传连接所提供的全能CD4+帮助通过直接对抗体反应的质量产生直接影响来提高疗效。我们假设该T辅助模块(HM)可以用作载体分子,以增强PVS25的免疫原性并诱导稳健的透射阻断免疫力。我们已经将编码HM编码HM的合成基因融合到编码PVS25的密码子优化的合成基因中。杂种基因已在大肠杆菌中成功表达,以正确折叠的构象。研究旨在(1)在小鼠中进行比较实验的测试,HM对PVS25免疫原性的影响,(2)评估恒河猕猴中新型嵌合构建体的安全性和免疫原性。将使用标准膜喂养测定法使用表达PVS25的P. berghei转基因寄生虫在体内测试传输阻断免疫力。这些研究的总体目标是表明HM可以用作免疫原性疟疾抗原的载体平台。鉴于疟疾对疟疾的巨大影响,人们越来越关注于维瓦克斯疟原虫的广泛和严重性质,并且迫切需要采取新颖的控制措施来减少传播,因此我们的建议有可能作为未来开发有效多阶段疫苗的框架。
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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Alberto Moreno其他文献
Alberto Moreno的其他文献
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{{ truncateString('Alberto Moreno', 18)}}的其他基金
Optimization of chimeric multi-stage immunogens for malaria vaccine development
用于疟疾疫苗开发的嵌合多阶段免疫原的优化
- 批准号:
8880440 - 财政年份:2014
- 资助金额:
$ 22万 - 项目类别:
Coadministration of capsid modified adenovirus for malaria vaccine development
衣壳修饰腺病毒联合给药用于疟疾疫苗开发
- 批准号:
8501354 - 财政年份:2012
- 资助金额:
$ 22万 - 项目类别:
Coadministration of capsid modified adenovirus for malaria vaccine development
衣壳修饰腺病毒联合给药用于疟疾疫苗开发
- 批准号:
8385810 - 财政年份:2012
- 资助金额:
$ 22万 - 项目类别:
Chimeric hybrid transmission blocking vaccine for malaria
疟疾嵌合混合传播阻断疫苗
- 批准号:
8243137 - 财政年份:2012
- 资助金额:
$ 22万 - 项目类别:
MODULAR CHIMERIC VACCINES TAILORED FOR MALARIA PARASITES
针对疟疾寄生虫的模块化嵌合疫苗
- 批准号:
8357458 - 财政年份:2011
- 资助金额:
$ 22万 - 项目类别:
MODULAR CHIMERIC VACCINES TAILORED FOR MALARIA PARASITES
针对疟疾寄生虫的模块化嵌合疫苗
- 批准号:
8172410 - 财政年份:2010
- 资助金额:
$ 22万 - 项目类别:
MODULAR CHIMERIC VACCINES TAILORED FOR MALARIA PARASITES
针对疟疾寄生虫的模块化嵌合疫苗
- 批准号:
7958235 - 财政年份:2009
- 资助金额:
$ 22万 - 项目类别:
MODULAR CHIMERIC VACCINES TAILORED FOR MALARIA PARASITES
针对疟疾寄生虫的模块化嵌合疫苗
- 批准号:
7715837 - 财政年份:2008
- 资助金额:
$ 22万 - 项目类别:
Modular Chimeric Vaccines tailored for malaria parasites
针对疟疾寄生虫量身定制的模块化嵌合疫苗
- 批准号:
7468359 - 财政年份:2006
- 资助金额:
$ 22万 - 项目类别:
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