- RFP Year2018
- Awarded Amount$930,571
- Development StageLead Optimization
- Collaboration PartnersEhime University, iBET, European Vaccine Initiative (EVI)
Nagaoka H, Kanoi BN, Ntege EH, Aoki M, Fukushima A, Tsuboi T, Takashima E. Antibodies against a short region of PfRipr inhibit Plasmodium falciparum merozoite invasion and PfRipr interaction with Rh5 and SEMA7A. Sci Rep. 2020 Apr 20;10(1):6573. doi: 10.1038/s41598-020-63611-6. PMID: 32313230; PMCID: PMC7171142.
Introduction and Background of the Project
Despite intensive control efforts over the past decade, malaria remains one of the most significant global public health problems, leading to substantial morbidity and mortality. Given the low efficacy and other potential limitations of the currently most advanced malaria vaccine candidate (RTS,S, or Mosquirix), a more effective second-generation malaria vaccines is urgently needed. In this proposal, we plan to advance the development of a novel blood-stage antigen that in the future may form part of a more effective multi-antigen-multistage malaria second-generation malaria vaccine.
Goal of this project is to further advance the development of a new asexual blood-stage malaria vaccine candidate, based on the PfRipr5 protein of the malaria parasite Plasmodium falciparum, which was discovered by researchers in Ehime University in collaboration with Sumitomo Dainippon Pharma Co., Ltd., Japan. Different expression systems for the antigen will be tested and compared, subsequently the immunogenicity of the antigen formulated with two different adjuvants already in use in humans will be tested in different model systems.
The project work plan has been structured according to the three research objectives defined. First objective will be to produce the PfRipr5 antigen in different scalable expression systems, with the ultimate goal to identify the expression system most suitable for further product development. Subsequently, objective two aims to formulate the antigen with two different adjuvants. Third and last objective of the project will be to evaluate the immunogenicity and anti-malarial efficacy of the adjuvanted in an animal model and in in in vitro growth inhibition assay.
How can your partnership (project) address global health challenges?
Malaria remains a very significant global public health problem especially in Africa, certain parts of Asia and the Americas, causing substantial morbidity and mortality. In fact, compared to the previous years, there has been no further decrease in the malaria disease burden in the last few years compared to previous ones, meaning that the improvements made in disease control might have stalled. The reduction and finally eradication of malaria will require a comprehensive and integrated control strategy of which vaccines –the most cost effective and easily administered means of controlling infectious diseases– represent a key technology. Hence, this project aims to contribute to the development of a more effective second-generation malaria vaccine as part of this public health strategy.
What sort of innovation are you bringing in your project?
Development of effective asexual blood-stage malaria vaccine antigens so far has been hampered by the high polymorphism levels in this kind of Plasmodium falciparum antigens, often resulting in strain-specific immunity that reduces vaccine efficacy in clinical trials. In contrast, the antigen targeted in this proposal is a highly conserved and novel asexual blood-stage vaccine candidate antigen that promises to overcome the limitations faced so far with blood-stage antigens. Moreover, the immune response to PfRipr shows a strong association with clinical protection against malaria. Finally, in our studies the antigen will be formulated with different adjuvants which we expect will further enhance the immunogenicity of this antigen.
Role and Responsibility of Each Partner
The project will be implemented under overall responsibility for coordination of management by European Vaccine Initiative (EVI) which will also be responsible for the formulation development of the adjuvants. iBET will be in charge of comparing different scalable expression system for the antigen production, whereas Ehime University will be mainly responsible for evaluating the vaccine candidate´s immunogenicity and anti-malarial efficacy and for developing corresponding assay systems.
Others (including references if necessary)
World Health Organization (WHO). World Malaria Report 2018. Geneva: WHO; 2018.