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病因，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选择性，并且依赖于人类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，并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）的II区与DARC结合。PvDBPII抗体抑制寄生虫入侵，但疫苗开发的主要障碍是产生高滴度的功能性抗体来预防疾病。在本项目中，我们将确定PvDBPII是否可以通过与HepB核心抗原颗粒结合来增强免疫原性，并研究通过暴露预测的DARC相互作用位点和覆盖脱靶多态性表位来定向重组蛋白，是否可以进一步集中抗体反应。

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.