Immunological characterization of the P. vivax DBP

间日疟原虫 DBP 的免疫学特征

基本信息

批准号：
7890559
负责人：
John H Adams
金额：
$ 69.7万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-08-01 至 2013-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7890559
关键词：
Address Africa Age Alanine Alleles Amino Acid Substitution Amino Acids Anemia Antibodies Antibody Formation Antigens Appearance B-Lymphocyte Epitopes Bacteriophages Binding Binding Proteins Binding Sites Biological Assay Blood Blood Group Antigens Child Clinical Cysteine Developing Countries Development Disease Drug resistance Epitope Mapping Epitopes Erythrocytes Genes Genetic Polymorphism Goals Human Immune Immune Sera Immune response Immunity In Vitro Infection Knowledge Libraries Life Cycle Stages Ligands Location Low Birth Weight Infant Malaria Modeling Molecular Monoclonal Antibodies Morbidity - disease rate Natural Immunity Orthologous Gene Parasites Pathway interactions Persons Plasmodium Plasmodium vivax Play Pregnant Women Prevalence Property Protein Region Reagent Research Personnel Risk Role Site-Directed Mutagenesis Specificity Staging Structure Surface Transcend Vaccines Variant Virulent Vivax Malaria base efficacy testing erythrocyte receptor polyclonal antibody programs receptor receptor binding three dimensional structure vaccine candidate vaccine development

Address Africa Age Alanine Alleles Amino Acid Substitution Amino Acids Anemia Antibodies Antibody Formation Antigens Appearance B-Lymphocyte Epitopes Bacteriophages Binding Binding Proteins Binding Sites Biological Assay Blood Blood Group Antigens Child Clinical Cysteine Developing Countries Development Disease Drug resistance Epitope Mapping Epitopes Erythrocytes Genes Genetic Polymorphism Goals Human Immune Immune Sera Immune response Immunity In Vitro Infection Knowledge Libraries Life Cycle Stages Ligands Location Low Birth Weight Infant Malaria Modeling Molecular Monoclonal Antibodies Morbidity - disease rate Natural Immunity Orthologous Gene Parasites Pathway interactions Persons Plasmodium Plasmodium vivax Play Pregnant Women Prevalence Property Protein Region Reagent Research Personnel Risk Role Site-Directed Mutagenesis Specificity Staging Structure Surface Transcend Vaccines Variant Virulent Vivax Malaria base efficacy testing erythrocyte receptor polyclonal antibody programs receptor receptor binding three dimensional structure vaccine candidate vaccine development

展开

项目摘要

DESCRIPTION (provided by applicant): Malaria caused by Plasmodium vivax is responsible for substantial morbidity in developing countries, producing 75-90 million cases of clinical malaria each year. Increasing prevalence of drug resistance in P. vivax, its global distribution and the appearance of more virulent forms of vivax malaria emphasizes the need for development of vaccines against this disease. Vivax malaria severely incapacitates infected persons, causing severe anemia, especially in young children, and an increased risk of low-birth-weight babies in pregnant women. Immunity to erythrocyte invasion ligands plays the critical role in controlling the blood-stage infection of P. vivax, since this malaria parasite does not sequester. Only persons that express the Duffy blood group antigen are infected with blood-stage P. vivax. Recognition of this human erythrocyte surface receptor is dependent upon the Duffy binding protein (DBP) cysteine-rich ligand domain, also known as region II or Duffy binding-like (DBL) domain. This essential interaction is a critical weakness in the parasite's life cycle. The major obstacle for developing this antigen as an effective vaccine is its high degree of polymorphism that makes ineffective the normal immune response following infection. Understanding the DBP-DARC interaction provides a model for all erythrocytes binding domains for Plasmodium-erythrocyte interaction. The specific aims will define the immunological and functional properties of the DBP ligand domain and identify functionally conserved determinants of the receptor-binding site that are able to induce a broadly inhibitory antibody response capable of inhibiting blood-stage development of Plasmodium vivax.

描述（由申请人提供）：疟疾疟原虫引起的疟疾造成了发展中国家的大量发病率，每年产生75-9亿例临床疟疾病例。耐药菌耐药性的患病率的增加，其全球分布和更具毒物形式的毒物疟疾的出现强调了针对这种疾病的疫苗开发的需求。 Vivax疟疾严重丧失了感染的人，造成严重的贫血，尤其是在幼儿中，并且孕妇低出生体重的风险增加。对红细胞浸润配体的免疫力在控制疟原虫的血液阶段感染中起着至关重要的作用，因为该疟原虫没有隔离。只有表达达菲血型抗原的人才被血液阶段假子感染。对这种人红细胞表面受体的识别取决于达菲结合蛋白（DBP）富含半胱氨酸的配体域，也称为区域II或Duffy结合（DBL）结构域。这种基本互动是寄生虫生命周期中的关键弱点。将这种抗原作为有效疫苗开发的主要障碍是其高度多态性，使感染后的正常免疫反应无效。了解DBP-DARC相互作用为所有红细胞结合结构域提供了一个模型，用于疟原虫相互作用。具体目的将定义DBP配体结构域的免疫和功能特性，并识别受体结合位点的功能保守决定因素，这些决定因素能够诱导能够抑制Vivax疟原虫血液阶段发展的广泛抑制性抗体反应。