Analysis of erythrocyte surface recognition mechanism by Plasmodium falciparum Ripr

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16629
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: Ehime University
• Principal Investigator: NAGAOKA HIKARU 愛媛大学, プロテオサイエンスセンター, 研究員 (10757222)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: マラリア / ワクチン / モノクローナル抗体 / コムギ無細胞

Outline of Final Research Achievements

Plasmodium falciparum malaria afflicts an estimated 205-316 million people annually, with an estimated 400,000 deaths. The development of a blood-stage vaccine against the disease is urgently needed. This research aimed to establish mouse monoclonal antibodies against the P. falciparum Ripr 1-5, a promising blood-stage vaccine target preventing merozoite invasion to the erythrocyte. The 11 monoclonal antibodies were selected from 51 clones by the reactivity to the cultured parasites using IFA. Then, we characterized the clones with SPR to reveal the affinity to PfRipr 1-5, and growth inhibition activity to the cultured parasites. In conclusion, we have established 4 monoclonal antibodies. The monoclonal are useful for quality control of PfRipr1-5 antigen in the development of the vaccine. Characterization of structural epitopes is essential for further study, identifying the mode of action of the antibodies and exploring the molecular mechanisms of merozoite invasion.

Free Research Field

寄生虫学

Academic Significance and Societal Importance of the Research Achievements

マラリアは、毎年2億人あまりが罹患し約40万人が死に至る感染症で、マラリアワクチンの実現は喫緊の課題である。近年我々は優れたワクチン候補分子であるRipr、そしてそのワクチン活性責任部位(Ripr1-5)を見出すことに成功し、現在Ripr1-5を抗原としたワクチンを前臨床開発中である。しかし依然として、Ripr1-5抗原のさらなる改良をする必要性は非常に高い。本研究で得られた４種類の抗Ripr1-5モノクローナル抗体の原虫侵入阻害を分子レベルに明らかにすることで、Riprの機能と構造、またRiprに関与するメロゾイト侵入メカニズムに立脚したワクチン開発が可能となり、マラリア撲滅を加速できる。