Awarded Amount$699,652DiseaseMalariaInterventionVaccineDevelopment StageAntigen IdentificationCollaboration PartnersEhime University , Mahidol University
Introduction and Background of the Project
Malaria caused by Plasmodium vivax is a leading tropical disease in Southeast Asia, South Asia, Mesoamerica, South America, and Oceania. The disease poses a major challenge for the global malaria eradication because P. vivax can cause recurring blood infections. These ‘relapses’ are caused by hypnozoites, the latent form of the parasite which can persists for a long time in the liver even after clearance of blood infection by anti-malarial drugs. Interventions that directly or indirectly reduce the hypnozoite reservoir in the affected communities, including new vaccines that block parasite transmission, will be highly required. Although vaccines are the most cost-effective tools to fight many infectious diseases, malaria vaccine targeting P. vivax is still not available.
This project aims to develop a novel mRNA-based malaria transmission-blocking vaccine of P. vivax. It targets Pvs230, a sexual stage protein of the parasite, that induces potent and long-lasting transmission blocking immunity and is able to interrupt transmission of P. vivax from human to mosquito.
We will combine the expertise in malaria vaccine development from Mahidol and Ehime Universities to generate new mRNA vaccines that block transmission of P. vivax. The vaccine target is the parasite protein called Pvs230, a well-known vaccine candidate expressed during the sexual-stage development of the parasite. Since Pvs230 is a large protein, we will first screen several Pvs230 fragments to identify the subdomain that induces strongest functional immunity. Then we will employ both the classical linear nucleoside-modified mRNA and our newly developed circular mRNA to devise the best performing vaccine construct. Vaccine efficacy will be determined by the ability of the vaccine to induce antibodies that block transmission of the parasite from humans to mosquitoes.
How can your partnership (project) address global health challenges?
Malaria continues to place a heavy toll on human health in low- and middle-income countries. The WHO’s Global Technical Strategy for Malaria (2016–2030) aims to eliminate malaria in a further 35 countries by 2030 compared to 2015. Through a single mosquito bite, P. vivax can cause recurring malaria episodes, making it difficult to control and eliminate. A vaccine that interrupts parasite transmission is expected to be an essential tool that helps eliminate the disease.
Short-term Impact: We will develop an mRNA vaccine that elicits potent transmission-blocking immunity in mice. The vaccine will be the basis for further development and evaluation in nonhuman primates and humans.
Long-term Impact: We aim to eventually combine potent transmission-blocking vaccine with a pre-erythrocytic vaccine in a multi-valent vaccine formulation to block transmission both from humans to mosquitoes and from mosquitos to humans. Such a combination vaccine is expected to quickly bring malaria transmission to cessation and thereby accelerate malaria eradication.
What sort of innovation are you bringing in your project?
To date, two transmission-blocking vaccines for P. vivax utilized recombinant Pvs25 protein were tested in human volunteers, but the results were disappointing due to the low immunogenicity and adverse events. Thus, there is a need to develop better vaccines. Nucleoside-modified mRNA formulated with lipid nanoparticle (mRNA-LNP) recently emerged as an effective vaccine platform for COVID-19. In this project, we will apply this well-established mRNA technology to help develop a new malaria transmission-blocking vaccine using Pvs230 as a target. In addition to this, we will also explore the use of circular mRNA which can potentially provide better vaccine stability, enhanced immunogenicity, and lower costs of production.
Role and Responsibility of Each Partner
In this project, Ehime University will lead the target and antigen selection, experiment planning, recombinant protein production for immunogenicity testing, and data analysis. Mahidol University will be responsible for project administration, mRNA vaccine design and production, immune response characterization, and functional assays to evaluate the vaccine potency using field isolates.
Others (including references if necessary)
WHO Global Technical Strategy for Malaria 2016-2030.
Development of a potent Pvs230 mRNA vaccine to block transmission of P. vivax