Introduction and Background of the Project

Introduction

The human complement system is a part of the innate immune response and consists of a cascade of enzymes that attack pathogens. It can act alone but it also enhances the efficacy of antibodies. Recent data suggest that Plasmodium falciparum, the causative agent of malignant malaria, can use the complement system for its own advantage to invade red blood cells and, in addition, it can recruit host complement regulators to protect itself from complement attack. We hypothesize that parasite proteins involved in this interaction are potential targets of the vaccine development.

Project objective

Identification of P. falciparum proteins that interact with host complement regulators and evaluation of their potentials as vaccine targets.

Project design

P. falciparum proteins that interact with host complement regulators will be identified by pulldown assays, mass spectrometry, and proteome microarray analysis. Recombinant proteins for the identified proteins will be produced and their binding capacity to the complement regulators will be evaluated. Specific antibodies against recombinant proteins will be produced and their effect on parasite viability and red blood cell (RBC) invasion capacity will be evaluated.

How can your partnership (project) address global health challenges?

According to WHO, Plasmodium falciparum malaria is responsible for the deaths of around 438,000 worldwide in 2015. Commonly used anti malaria drugs are losing their effcitiveness due to anti malaria drug resistance in many places like in Africa. An highly effective vaccine against malaria will be an important tool towards achieving WHO goal to reduce mortality by ≥ 40% by 2020 and by ≥ 90% by 2030. Our study will fill a major gap in the vaccine development strategy which until now has ignored the parasite’s ability to evade complement and the identified proteins could serve as a single or a part of multicomponent highly effective malaria vaccine.

What sort of innovation are you bringing in your project?

The use of full P. falciparum proteome microarray with approximately 90% coverage of the entire protein coding genome to identify complex parasite protein ligands is a new and innovative approach to vaccine development. Antigen Discovery Inc. has developed 3D7 P. falciparum proteome microarray contains ~8,000 full length or fragmented proteins as a sole source.  

Role and Responsibility of Each Partner

José A. Stoute, MD, The Pennsylvania State University College of Medicine will serve as overall PI for the program. He will be in charge of identifying parasite protein ligands using pulldown assays and mass spectrometry. In addition, his laboratory will test the effect of antibodies against the protein ligands on parasite viability and RBC invasion capacity. Osamu Kaneko, MD, PhD, Institute of Tropical Medicine, Nagasaki University will lead the design of the protein expression plan and will produce recombinant proteins for testing and perform binding assay. Joseph Campo, PhD, Antigen Discovery, Inc. will direct the proteome microarray studies with samples provided by Dr. Stoute.

Others (including references if necessary)

https://www.ghvap.org/platforms/Pages/Antigen-Arrays.aspx