Development of a novel CSP monoclonal antibody that inhibits sporozoite migration in the skin and establishment of an effect measurement system against endemic strains for the development of a vaccine that prevents malaria parasite infection

Malaria is a parasitic disease that kills about 400,000 people a year, mainly in tropical regions. Malaria parasites (sporozoites), which are driven into the skin by blood-sucking infected mosquitoes, actively move and enter the bloodstream to reach and infect hepatocytes. Therefore, sporozoites are attracting attention as a target for preventing infection, but the first malaria vaccine that targets the surface protein CSP has problems such as insufficient efficacy in suppressing infection and severity of malaria. The purpose of this study is to demonstrate that sporozoites that migrate in the skin are good targets for inhibitory antibodies by producing novel CSP monoclonal antibodies and establishing an evaluation system. In this fiscal year, a novel CSP monoclonal antibody will be established and its effect of suppressing the movement of sporozoites in the skin/liver chip and the effect of suppressing infection will be examined. The study will also analyze the genetic polymorphisms of CSP in epidemic areas. Malaria is a parasitic disease that kills about 400,000 people a year, mainly in tropical regions. Malaria parasites (sporozoites), which are driven into the skin by blood-sucking infected mosquitoes, actively move and enter the bloodstream to reach and infect hepatocytes. Therefore, sporozoites are attracting attention as a target for preventing infection, but the first malaria vaccine that targets the surface protein CSP has problems such as insufficient efficacy in suppressing infection and severity of malaria. The purpose of this study is to demonstrate that sporozoites that migrate in the skin are good targets for inhibitory antibodies by producing novel CSP monoclonal antibodies and establishing an evaluation system. Also, the project will generate Plasmodium berghei expressing GFP and luciferase in the cytoplasm using CRISPR/Cas9-dependent homologous recombination for live imaging and quantitative analysis. In addition, in order to obtain a monoclonal antibody against CSP with an inhibitory effect, a His-tagged CSP protein was synthesized using a cell-free protein synthesis system derived from wheat germ. Prepare to express

Vaccines (Immune Correlates)

Apr 2021 — Mar 2024

Japan