Phase 1 Trial of Na-APR-1 and Na-GST-1 Hookworm Vaccines in Brazilian Adults
Na-APR-1 和 Na-GST-1 钩虫疫苗在巴西成人中的一期试验
基本信息
- 批准号:9107814
- 负责人:
- 金额:$ 77.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-08 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:Activities of Daily LivingAdjuvantAdultAdverse eventAffinityAgonistAlhydrogelAntibodiesAntibody AffinityAntibody FormationAntibody ResponseAntigensApplications GrantsAreaAutoimmunityB-LymphocytesBiological AssayBiological MarkersBiological Response Modifier TherapyBloodBrazilClinicalClinical TrialsDecision MakingDevelopmentDissociationDoseDouble-Blind MethodEnzyme-Linked Immunosorbent AssayFrequenciesFutureHealthHookwormsHumanHuman Subject ResearchHumoral ImmunitiesHypersensitivityIgG1IgG3IgG4Immune responseImmunizationImmunoglobulin GImmunologic AdjuvantsImmunologicsIndividualLawsLicensureLifeLife Cycle StagesLipid AMaintenanceMeasuresMemory B-LymphocyteMethodsMolecular WeightNecator americanusParasitesPhase I Clinical TrialsPhase II/III TrialPopulationProductionPropertyProtein SubunitsRecombinant ProteinsRecombinant VaccinesRecombinantsRegimenResourcesRiskRoleSafetySiteStagingSubunit VaccinesSurface Plasmon ResonanceSurrogate MarkersSystemTLR4 geneTechniquesTechnologyTestingTimeVaccinatedVaccine AntigenVaccinesViralVirusWorkantibody-dependent cell cytotoxicityatopyattenuationbasebiodefensedisability-adjusted life yearsenzyme linked immunospot assayfeedingimmunogenicityimmunoreactivityinnovationneglected tropical diseasesneutralizing antibodynovelnovel vaccinespathogenresponsevaccination schedulevaccine development
项目摘要
DESCRIPTION (provided by applicant): This U01 grant proposal will utilize a new paradigm for early assessment of new vaccine antigen combinations. It will utilize several state-of-the-art immunological technologies to determine the impact of co-administering the novel Na-GST-1 and Na-APR-1 (M74) hookworm vaccines on the immune response to each antigen in a Phase 1 clinical trial conducted in healthy adults living in a hookworm-endemic area of Brazil. The aim is to induce the highest specific neutralizing antibody response to each component of a future co-formulated product, preferably with an IgG1 and IgG3 subclass response with induction of antibodies of high affinity and a significant B-cell memory response. If co-administration does not result in increased safety risk and does not negatively impact the humoral immune response to either of the two antigens, work will proceed to develop a bi-component, coformulated vaccine that will be used in future clinical trials in hookworm-endemic sites. In addition, the proposed clinical trial will serve to optimize the component combinations that will go into the bi-component product early in clinical development, especially the addition of the immunostimulant GLA-AF, thus economizing on time, resources, and the number of subjects required in clinical trials. The result will enable earlier decision-making regarding the optimal components of a new vaccine, in turn accelerating the time to licensure and delivery to the populations in need living in hookworm endemic areas. In most cases, immune responses to vaccines are evaluated by standard technologies such as the indirect enzyme-linked immunosorbent assay (ELISA), virus neutralization, or radiometric antibody-dependent cell-mediated cytotoxicity assay. This is despite the fact that over the last decade several major advances in antibody profiling and B cell techniques have been made in related areas such allergy and atopy, autoimmunity, biotherapeutics, and biodefense. These include the ImmunoCAP method to quantify induced antibody levels, Surface Plasmon Resonance to investigate antibody affinity, and ELISPOT to quantify vaccine-induced specific memory B cells. The objective of this U01 proposal is to apply these advances early in the clinical development of a new vaccine for hookworm, one of the most prevalent and important of the Neglected Tropical Diseases, at a point when they can be used to predict the effect of combining antigens into a single vaccine product before a co-formulated vaccine is developed and tested in larger, more costly Phase 2 and 3 trials.
描述(由适用提供):该U01赠款提案将利用新的范式来早日评估新的疫苗抗原组合。它将利用几种最先进的免疫技术来确定新型的Na-GST-1和Na-GST-1和Na-APR-1(M74)钩虫疫苗对每种抗原的免疫响应的影响,该hook虫疫苗在居住在巴西hook虫区域的健康成人中进行的1期临床试验中对每种抗原的免疫响应的影响。目的是诱导对未来共同成型产品的每个组件的最高特异性中和抗体反应,最好使用IgG1和IgG3亚类反应,并诱导高亲和力的抗体和明显的B细胞记忆响应。如果共同给药不会导致安全风险增加,并且不会对两种抗原中的任何一种都产生负面影响,那么工作将继续开发双组分,配合式疫苗,该疫苗将在未来的钩虫 - 内态位点的临床试验中使用。此外,拟议的临床试验将有助于优化临床开发早期将进入双分量产品的组成组合,尤其是增加免疫刺激性GLA-AF,从而按时,资源和临床试验中所需的受试者数量进行节省。结果将使关于新疫苗的最佳组成部分的较早决策,进而加速了居住在钩虫内分子区域中有需要的人群的许可和交付的时间。在大多数情况下,通过标准技术(例如间接酶 - 连接的免疫吸附测定法(ELISA),病毒神经元化或放射抗体依赖性细胞介导的细胞介导的细胞毒性测定法)评估对疫苗的免疫回应。这是一个事实,在过去的十年中,在相关领域(如过敏和特纳科,自身免疫性,生物治疗剂和生物粘度)已经在抗体分析和B细胞技术方面取得了一些重大进展。其中包括量化诱导抗体水平的免疫方法,研究抗体亲和力的表面等离子体共振以及量化疫苗诱导的特定记忆B细胞的ELISPOT。该U01提案的目的是在钩虫的新疫苗的临床开发中应用这些进步,这是最普遍,最重要的热带疾病之一,在某种程度上,可以将它们用于预测将抗原结合到单个疫苗产品中的效果,然后在共同成型的疫苗中开发和测试较大的成本2阶段,更较大的成本2和3阶段的2阶段和3阶段和3阶段和3阶段和3阶段和3阶段。
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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David Joseph Diemert其他文献
David Joseph Diemert的其他文献
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{{ truncateString('David Joseph Diemert', 18)}}的其他基金
Planning for Experimental Infection Trial to Test Hookworm Vaccine Efficacy
规划实验性感染试验以测试钩虫疫苗功效
- 批准号:
8926594 - 财政年份:2015
- 资助金额:
$ 77.36万 - 项目类别:
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