Immunogen Design to enhance the efficacy of Plasmodium vivax vaccine

描述(由申请人提供)：间日疟原虫是非洲以外临床疟疾的主要原因，在发展中国家造成大量发病率和经济损失。间日疟原虫为入侵阻断疫苗方法提供了独特的机会，因为这种寄生虫对网织红细胞具有高度的选择性，并依赖于人类DARC蛋白进行入侵。这种选择性区分了间日疟原虫和恶性疟原虫，为开发入侵阻断疫苗提供了相当大的优势。间日疟原虫通过间日疟原虫Duffy结合蛋白(PvDBPII)中的II区与DARC结合。PvDBPII抗体可以抑制寄生虫的入侵，但疫苗开发的主要障碍是产生能够预防疾病的高滴度功能性抗体。在这个项目中，我们将确定PvDBPII是否可以通过与乙肝核心抗原颗粒结合来增强免疫原性，并研究是否可以通过将重组蛋白与预测的DARC相互作用位点定位并掩盖靶标外的多态表位来进一步聚焦抗体反应。 公共卫生相关性：间日疟原虫是东南亚和拉丁美洲许多地区临床疟疾的主要原因，并在发展中国家造成大量发病率和经济损失。本项目的目标是利用合理的免疫原设计，通过将PvDBPII重组蛋白连接到病毒样颗粒(VLP)上并对其进行定向，以最大限度地提高抗体对预测的DARC相互作用位点的反应性，从而提高间日疟原虫疫苗的效力。

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.