About this research groupWe focus on the clinical development of plasmodium falciparum vaccines for control and elimination of malaria. We explore mechanisms of parasite biology, and pursue identification of the immune signature of protection against malaria and the (clinical) development of candidate malaria vaccines.
The Malaria parasites research group has three focus areas.
This represents development and clinical testing of Plasmodium falciparum malaria vaccines and identification of immune correlates of protection.
Clinical development of malaria vaccines
This represents development and clinical testing of Plasmodium falciparum malaria vaccines and identification of immune correlates of protection. Research activities include studies in the Controlled Human Malaria Infection Model (see also malariavaccin.nl) as well as studies in naturally infected populations in malaria endemic countries.
Led by Benjamin Mordmüller.
Malaria parasites only have a single and abnormal mitochondrion, which is essential for the parasite's survival.
Biology of malariaMalaria parasites only have a single and abnormal mitochondrion, which is essential for the parasite's survival. Indeed, one of the most effective anti-malarial drugs, atovaquone, kills the parasite by targeting a mitochondrial protein.
- We aim to identify all of the estimated 400-500 mitochondrial proteins. Using this information, we will build a computational model that will allow the prediction of essential proteins.
- We will start to improve existing methods to modify the parasite DNA in order to remove genes with a role in mitochondria to study their function and verify the computer predictions.
- By comparing the experimentally validated malaria mitochondrial model with existing models of human mitochondria, we intend to identify suitable targets for new anti-malarial medicines.
Led by Taco Kooij.
In observational and intervention studies, we aim to understand and interrupt the transmission of P. falciparum.
Epidemiology of malariaIn observational and intervention studies, we aim to understand and interrupt the transmission of P. falciparum. The burden of malaria is unequally distributed in populations with some humans disproportionally receiving infected mosquito bites. We aim to understand what drives this transmission in terms of ecology, mosquito-to-human transmission and the human infectious reservoir for malaria.
For this purpose, we use serological and molecular tools to determine spatial patterns in disease transmission and directly assess human infectiousness to mosquitoes by mosquito feeding assays. With this set of tools, we explore the prevalence and epidemiological importance of submicroscopic malaria infections for disease transmission and malaria elimination.
Led by Teun Bousema.
The focus lies on the development of two types of malaria vaccines: attenuated whole sporozoite vaccines and transmission blocking vaccines.
Clinical development of malaria vaccines1. Attenuated whole sporozoite vaccines
An attenuated sporozoite vaccine should be safe in absolute absence of breakthrough blood infections while inducing complete protection. We generated deletion mutants deficient for essential genes for liverstage development. Our findings provide the foundation of the first genetically attenuated parasite for clinical testing (PfSPZ-GA1). We pioneered a highly efficient immunization protocol for complete and lasting protection in the controlled human malaria infection model (NEJM 2009, Lancet 2011). This will be translated into a vaccine product (PfSPZ-CVac).
2. Transmission blocking vaccines
Vaccines interrupting malaria transmission aim to reduce the spread of the parasites among humans by preventing infection of Anopheles vectors and represent essential tools for malaria elimination. Such vaccines are an essential tool for eradication. Our vaccine strategy is based on the Pfs48/45 protein only expressed and functionally involved in transmission stages. We have developed a first generation sub-unit of Pfs48/45 as vaccine candidate currently in cGMP production (R0-PF10C) for clinical testing. We are pioneering the next generation functional bioassay for transmission blocking antibodies by using luciferase-tagged cultured parasites for mosquito feeding and study parasite and mosquito factors involved in transmission.
Our spin-off company TropIQ aims for better tools for transmission studies.
Our work has demonstrated that submicroscopic gametocyte densities are highly common, frequently result in mosquito infections and can maintain malaria transmission in areas of low endemicity.
Epidemiology of malariaOur work has demonstrated that submicroscopic gametocyte densities are highly common, frequently result in mosquito infections and can maintain malaria transmission in areas of low endemicity. We further showed that adding transmission-blocking drugs to current malaria therapies can substantially reduce this transmission and aid malaria elimination strategies. The clustering of malaria infections in transmission hotspots may provide an attractive opportunity to target transmission-blocking interventions to these areas that are most important for maintaining transmission.