Accelerating discovery of an efficacious Plasmodium vivax multivalent multi-stage vaccine

加速发现有效的间日疟原虫多价多阶段疫苗

基本信息

批准号：
10526422
负责人：
John H Adams
金额：
$ 97.55万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
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：
2020-12-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10526422
关键词：
Acceleration Adjuvant Adult Africa Aliquot Animals Antibodies Antibody Response Antibody titer measurement Antigen Targeting Antigen-Presenting Cells Antigens Binding Binding Proteins Biological Assay Blood Cells Clinical Collaborations Country Cryopreservation Culicidae Development Ensure Epitope Mapping Epitopes Erythrocytes Formulation Future Geographic Locations Goals Growth Healthcare Hepatocyte Human Immune Immune Sera Immune response Immunity Immunization Immunize Immunoassay Immunologics In Vitro Individual Infection Infection prevention Laboratories Laboratory Animals Limited Stage Liver Malaria Malaria Vaccines Maps Methods Modeling Monoclonal Antibodies Mus Myanmar Nature Parasites Parasitic infection Persons Peru Plasmodium falciparum Plasmodium vivax Process Productivity Property RNA RNA vaccine Recombinants Relapse Risk Seasons Source Sporozoites Subunit Vaccines Thailand Transgenic Organisms Vaccination Vaccine Antigen Vaccine Design Vaccines Validation Vivax Malaria Work breakthrough infection candidate validation cell type cost estimate design experimental study global health immunogenicity immunoreactivity in vitro Assay migration nanoparticle prevent protective efficacy transmission process transmission-blocking vaccine uptake vaccine candidate vaccine delivery vaccine development vaccine strategy vaccinology

项目摘要

Project Summary/Abstract Plasmodium vivax is the second leading cause of malaria and the most prevalent cause of malaria outside of Africa. The estimated cost of the global burden of vivax malaria is $1.4 - $4 billion per year and more people live at risk worldwide from P. vivax than P. falciparum. It is endemic mostly in poor countries where access to affordable health care is lacking, which leads to lost adult productivity. Relapse infections from P. vivax poses a special challenge to malaria elimination and eradication because of its ability to repeatedly restart blood-stage infections from hypnozoites – the dormant parasite that can persist in human livers from weeks to years after the sporozoite infection. Exacerbating the problem, P. vivax transmission occurs prior to onset of clinical signs and treatment options to clear relapsing parasites in the dormant liver stage are limited. The goal of this U01 project is to accelerate vivax malaria vaccine development by validation of an optimal combination of P. vivax target antigens in pre-erythrocytic stages. Our vaccine strategy seeks to validate candidate antigens that together can effectively inhibit sporozoite infection and block liver stage development, including blood stage breakthrough infection. Our strategy exploits our new in vitro functional assay for experimental studies of liver stage development of P. vivax. We will pursue a structural vaccinology approach, using broadly neutralizing binding inhibitory antisera and monoclonal antibodies to identify and characterize the highest value immunogens and vaccine delivery method to design a multivalent vaccine to prevent and eliminate vivax malaria.

项目摘要/摘要疟原虫是疟疾的第二大主要原因，也是最普遍的疟疾原因非洲。来自P. vivax的风险比恶性疟原虫居住。缺乏负担得起的医疗保健，这导致成人prolt Prolt Productity失去。对消除疟疾的挑战和根除案例构成了一个反复重新启动的能力催眠型的血液阶段感染 - 休眠寄生虫，可以从几周开始持续在人类肝脏中为了加剧速度的孢子岩感染。在休眠期间清除复发寄生虫的临床体征和信任选择是有限的该U01项目的目标是通过验证最佳的疫苗开发疫苗疫苗的开发植入前阶段的叶疟原虫靶标的组合。候选抗原可以有效地抑制孢子虫抑制IND障碍物肝阶段开发，包括血液流血阶段的突破性感染。用于肝脏阶段发育的经验测定。方法，使用广泛中和结合结合抑制性抗血清和单克隆抗体来识别和表征最高价值免疫原和疫苗输送方法来设计多价疫苗预防和消除Vivax疟疾。