Introduction and Background of the Project

Introduction

Despite intensive control efforts over the past decade, malaria remains one of the most significant global public health threats, leading to substantial morbidity and mortality. Given the limitations of the currently most advanced malaria vaccine candidate (RTS,S, or Mosquirix), including low efficacy, more effective second-generation malaria vaccines are urgently needed. In this proposal, we build on the success of the previous GHIT-funded T2018-151 project to further advance the development of a blood-stage malaria vaccine candidate based on PfRipr5; this novel antigen may be part of a more effective multi-antigen-multistage second-generation malaria vaccine in the future.

Project objective

This project will build on the established successful collaboration between the partners to further advance the development of the PfRipr5 malaria vaccine candidate. The main objectives are to:

1.   Establish a process for PfRipr5 production compliant with current Good Manufacturing Practice (cGMP)

2.   Produce PfRipr5 for safety-toxicology study according to cGMP

3.   Perform a safety-toxicology study to evaluate PfRipr5 formulated with the SA-1 adjuvant

4.   Prepare the dossier for Phase I/IIa clinical trial

Project design

The project workplan has been structured according to the four research objectives defined above. In objective 1, the production and purification processes of PfRipr5 will be fine-tuned using the optimal expression system identified in the previous project (T2018-151). In objective 2, the established manufacturing process will be transferred to the selected CDMO, where PfRipr5 will be produced in accordance with cGMP. PfRipr5 will be formulated with SA-1 and further evaluated in a pre-clinical GLP safety-toxicology study (objective 3). Finally, under objective 4, the clinical trial documentation will be prepared for subsequent ethical and regulatory approval to conduct a Phase I/IIa clinical trial.

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. The disruption of malaria prevention, diagnosis and treatment that occurred during the COVID-19 pandemic, led to an increase in malaria burden in 2021 compared with 2019 in most moderate and high transmission countries, especially in sub-Saharan Africa (WHO World Malaria Report 2022). The reduction and finally eradication of malaria will require a comprehensive and integrated control strategy in which vaccines – the most cost effective and easily administered means of controlling infectious diseases – represent a key technology. Therefore, the research activities planned within this project will 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 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. In addition, this project employs a novel TLR7 adjuvant (SA-1) to induce a potent and durable effect.

Role and Responsibility of Each Partner

The project partners have long-standing collaboration histories and will bring complementary expertise to ensure the successful completion of the proposed activities. The European Vaccine Initiative (EVI) will be responsible for overall coordination and management and will lead clinical protocol development and dossier preparation required for future ethical/regulatory submissions. Ehime University (Ehime) will further characterize the PfRipr5 recombinant protein with multiple analytical methods and dissect mode of action of the produced antibodies, focusing on the functional Growth Inhibition Assay (GIA). Sumitomo will be responsible for providing the SA-1 adjuvant, evaluating vaccine immunogenicity in animal studies, and overseeing the safety-toxicology study. iBET will be responsible for final process development, technology transfer to the CDMO and cGMP manufacturing oversight.

Others (including references if necessary)

World Health Organization (WHO). World Malaria Report 2022. Geneva: WHO; 2022.