Introduction and Background of the Project

Introduction

Malaria caused by Plasmodium vivax is a major neglected tropical disease that affects 35 countries, disproportionately impacting remote populations. The disease poses a major challenge for global malaria eradication due to the parasite’s ability to become dormant in the liver of infected individuals for months to years before reactivation. The reservoir of these dormant parasites, known as hypnozoites, not only causes recurring blood infections but also sustains transmission in the communities. Implementing existing drug treatments and vector control measures is often difficult in many areas, allowing transmission to persist. Vaccination offers a promising, cost-effective alternative for malaria elimination. New vaccines that can reduce both infection and transmission in the affected communities will be highly important. Currently, there is no malaria vaccine for P. vivax.

Project objective

This project aims to develop a multistage mRNA vaccine capable of reducing both infection and transmission of P. vivax

Project design

Researchers from Mahidol, Chulalongkorn, and Ehime Universities are teaming up to develop a new mRNA vaccine that can both prevent infection and stop the spread of P. vivax. The vaccine will target two key proteins: PvCSP, which is involved in the early stages of infection, and Pvs230, which helps the parasite spread from humans to mosquitoes. The team will first test different versions of the PvCSP mRNA to find the most promising one, then fine-tune the best combination of PvCSP and Pvs230. Promising vaccine formulas will be tested in non-human primates to identify the most effective option. Once a lead candidate is selected, they will produce a high-quality vaccine suitable for human trials. All vaccine versions will use a clinically proven lipid nanoparticle (LNP) system to deliver the mRNA. Success will be evaluated by the vaccine’s ability to generate antibodies that block the parasite from infecting liver cells and prevent its transmission to mosquitoes.

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

Malaria remains a major global health threat, despite being both preventable and treatable. It continues to strain healthcare systems and slow economic progress, especially in low- and middle-income countries. The World Health Organization’s Global Technical Strategy for Malaria (2016–2030) sets ambitious goals, including a 90% reduction in cases and deaths, and elimination of the disease in 35 countries by 2030. As countries make progress, the focus must shift from treating infections to stop their spread. Our project aims to support this transition by developing an effective vaccine specifically targeting Plasmodium vivax, a major challenge in malaria elimination efforts.

Short-term impact: A vaccine against P. vivax could dramatically reduce the financial and healthcare burdens on endemic countries. Governments spend large amounts on diagnosis, treatment, and hospital care for this type of malaria. Additionally, individuals can miss 4 to 15 days of work or school with each infection, affecting family income and education. Repeated infections also lead to long-term health issues like anemia and malnutrition. A vaccine could help prevent these setbacks and improve quality of life.

Long-term impact: In the long run, a P. vivax vaccine could revolutionize malaria elimination efforts. Unlike other malaria species, P. vivax can hide in the liver and cause relapses, making it especially hard to control. By combining vaccination with existing tools like mosquito control and case management, we can break the cycle of transmission. This would pave the way for lasting elimination, boost economic development, reduce inequalities between affected and non-affected regions, and strengthen the world’s ability to respond to future outbreaks.

What sort of innovation are you bringing in your project?

Our project introduces a novel, multi-pronged approach to creating a powerful mRNA-based vaccine targeting Plasmodium vivax. So far, PvCSP has shown the most promise as a vaccine candidate targeting the early (pre-erythrocytic) stage of the parasite’s life cycle. In previous research supported by GHIT, we also identified new Pvs230 constructs that can completely block parasite transmission, an exciting breakthrough. Because Pvs230 appears during the parasite’s sexual development stage, it can stimulate stronger immune responses through natural exposure, making it an excellent vaccine target. This project combines three cutting-edge technologies to create an effective multivalent vaccine:

Wheat Germ Cell-Free System (WGCFS): This platform enables the production of high-quality malaria proteins for analysis and refinement of the immune response.

Advanced mRNA Vaccine Platform: This flexible system supports rapid design, testing, and optimization of vaccines that can target multiple parasite proteins at once.

Robust Cell-Based Assays: These tools help us accurately assess how well the vaccine candidates work, particularly in stopping the parasite before it infects liver cells.

Together, these innovations offer a powerful path forward in the fight to eliminate P. vivax malaria.

Role and Responsibility of Each Partner

Mahidol University will oversee project coordination, carry out data generation and analysis, characterize immune responses, and conduct functional assays to assess vaccine efficacy. Ehime University will take the lead in selecting target antigens, producing recombinant proteins for immunogenicity testing, and participating in data generation and analysis. Chulalongkorn University will be primarily responsible for designing and producing the mRNA vaccine, including GMP manufacturing, as well as contributing to data generation and analysis. All institutions will contribute to the overall study design.

Others (including references if necessary)

Global technical strategy for malaria 2016-2030, 2021 update

https://www.who.int/publications/i/item/9789240031357