Immunogen Design to enhance the efficacy of Plasmodium vivax vaccine

增强间日疟原虫疫苗功效的免疫原设计

基本信息

批准号：
7881375
负责人：
JOSEPH D SMITH
金额：
$ 24.61万
依托单位：
SEATTLE BIOMEDICAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7881375
关键词：
Adjuvant Africa Antibodies Antibody Formation Antigen Receptors Antigens Binding Binding Proteins Binding Sites Biological Assay Blocking Antibodies Carrier Proteins Clinical Conjugate Vaccines Coupling Cover-up Cysteine Development Disease Drug Formulations Economics Electron Microscopy Enhancing Antibodies Enzyme-Linked Immunosorbent Assay Epitopes Gel Goals Haplotypes Human Immunization In Vitro Latin America Life Cycle Stages Link Location Lysine Malaria Molecular Weight Morbidity - disease rate Mus Oryctolagus cuniculus Parasites Plasmodium falciparum Plasmodium vivax Plasmodium vivax vaccine Preparation Proteins Recombinant Proteins Reticulocytes Running Serum Site Southeastern Asia Structure Sucrose Testing Vaccines Virus-like particle chemokine design immunogenic immunogenicity monomer novel parasite invasion particle prevent public health relevance research study vaccine development vaccine efficacy

项目摘要

DESCRIPTION (provided by applicant): Plasmodium vivax is a major cause of clinical malaria outside of Africa and causes substantial morbidity and economic loss in the developing world. P. vivax presents unique opportunities for invasion blocking vaccine approaches because the parasite is highly selective for reticulocytes and depends on the human DARC protein for invasion. This selectivity differentiates P. vivax from P. falciparum, and provides considerable advantages for development of invasion blocking vaccines. P. vivax binds to DARC via the region II in the P. vivax Duffy binding protein (PvDBPII). Antibodies to PvDBPII inhibit parasite invasion, but the main obstacle to vaccine development is generating high titer functional antibodies that will prevent disease. In this project, we will determine if PvDBPII immunogenicity can be enhanced by conjugating to HepB core antigen particles and investigate whether the antibody response can be further focused by orienting the recombinant protein with the predicted DARC interaction site exposed and covering up off-target polymorphic epitopes. PUBLIC HEALTH RELEVANCE: Plasmodium vivax is a major cause of clinical malaria in many parts of Southeast Asia and Latin America and causes substantial morbidity and economic loss in the developing world. The goal of this project is to use rational immunogen design to enhance the efficacy of a P. vivax vaccine by conjugating PvDBPII recombinant protein on virus-like particles (VLP) and orienting the protein so as to maximize antibody reactivity to the predicted DARC interaction site.

描述（由申请人提供）：Vivax疟原虫是非洲以外临床疟疾的主要原因，并导致发展中国家的大量发病率和经济损失。 Vivax为入侵提供了独特的机会阻止疫苗方法，因为寄生虫对网状细胞具有很高的选择性，并且取决于人类DARC蛋白的入侵。这种选择性将假霉菌与恶性疟原虫区分开来，并为开发入侵阻断疫苗提供了可观的优势。 Vivax在Vivax Duffy结合蛋白（PVDBPII）中通过区域II与DARC结合。 PVDBPII的抗体抑制了寄生虫的侵袭，但是疫苗发育的主要障碍是产生可预防疾病的高滴度功能抗体。在该项目中，我们将通过将HEPB核心抗原颗粒缀合，并研究是否可以通过将重组蛋白与预测的DARC相互作用取向预测的DARC相互作用，并掩盖todarget多晶型多态性相位效应，从而确定是否可以通过将PVDBPII免疫原性增强，并研究是否可以进一步关注重组蛋白。公共卫生相关性：在东南亚和拉丁美洲的许多地区，疟原虫是临床疟疾的主要原因，并在发展中国家造成了大量的发病率和经济损失。该项目的目的是利用有理免疫原设计来通过在病毒样颗粒（VLP）上结合PVDBPII重组蛋白（VLP）来增强疟原虫疫苗的功效，并取代蛋白质，从而最大程度地提高对预测的DARC相互作用位点的抗体反应性。