International clinical activities

Sleep in Malaria (SLiMA)

Funded by the German Research Foundation (DFG - Deutsche Forschungsgemeinschaft) and conducted in collaboration with the Ludwig-Maximilians-Universität München (LMU, Germany) and the Centre de Recherche Médicales de Lambaréné (CERMEL, Gabon), we investigate the impact of malaria on sleep and how different sleep patterns affect the immune response to malaria. The effects of this interplay on sickness behavior, host defense mechanisms, the recovery process and disease are evaluated by an interdisciplinary group of parasitologists, sleep experts and immunologists. One of the first sleep laboratories in Central Africa has been set up at CERMEL, Gabon for this project.

PRISM

Our understanding of malaria immunity and the spread of malaria infections can benefit greatly from in-depth epidemiological studies in malaria endemic countries. In Uganda, we undertake such studies with a multi-disciplinary team of researchers from the Kampala, Nijmegen, London, Liverpool and San Francisco. Our work aims to understand all aspects of malaria transmission using tools ranging from genomic surveillance to social science. Researchers from Radboudumc specifically study the development of malaria transmission stages, infectivity to mosquitoes and immune responses that can prevent mosquitoes from becoming infected. These questions are being addressed in large longitudinal studies where individuals living in malaria endemic areas in Uganda are followed for several years under natural malaria exposure. 
Funded through the US National Institutes of Health (NIH) and the European Research Council (ERC-Consolidator Grant) this project aims at supporting malaria policy in Uganda by frequent interactions with local and international policy makers.

Malaria transmission blocking vaccine

In 2019 a Plasmodium falciparum Malaria Transmission Blocking Vaccine Consortium was formed to develop and test malaria transmission blocking vaccines. The activities of this consortium are funded through EDCTP2, a funding scheme of the European & Developing Countries Clinical Trials Partnership (EDCTP). Radboudumc led the establishment of the first P. falciparum malaria transmission model in Sub-Saharan Africa. This Controlled Human Malaria Infection and Transmission (CHMI-Trans) model is established in collaboration with the consortium coordinator, the Parasites and Microbes Research & Training Center (PMRTC) at the Université des Sciences, des Techniques et des Technologies de Bamako (USTTB) in Bamako, Mali. This CHMI-Trans model was recently used in a clinical trial to evaluate a novel malaria transmission blocking vaccine candidate.

Vaccines against Plasmodium vivax malaria

Plasmodium vivax is the most widespread human malaria with 2.5 billion people living at risk in South America, Asia, Africa and Oceania. Vaccines will be crucial for reducing the burden of this P. vivax malaria. 
Funded through the Horizon Europe research funding scheme of the European Commission, the international OptiViVax consortium coordinated by Radboudumc together with the University of Oxford, aims at integrating ambitious multi-disciplinary scientific and clinical approaches around the parasite’s lifecycle and P. vivax immuno-biology to further develop next-generation vaccines with improved efficacy. Controlled Human Malaria Infection models will be used to benchmark lead vaccine candidates and their potential for being tested in future field trials. 
Radboudumc will establish a P. vivax Controlled Human Malaria Infection Transmission model and apply this model for assessing P. vivax transmission blocking vaccines in a Phase 1 study.

Transmission networks of malaria infections

For malaria control efforts, it is important to understand who forms the source of new malaria infections. This can be done indirectly, by quantifying how infectious individuals are to mosquitoes and extrapolating the likely contribution to onward transmission. However, it can also be done more directly by studying patterns of malaria infections in space and time. In The Gambia, clinical and asymptomatic infections are being monitored over the course of several transmission seasons. Using a large panel of genetic parasite markers and information on the occurrence of malaria infections in space and time, we establish transmission networks where we identify the most likely source of newly detected infections.
Funded through the Bill & Melinda Gates Foundation and the European Research Council (ERC-Consolidator Grant) this project aims at providing evidence for international policy makers on the relative importance of asymptomatic malaria infections and low-density infections for malaria transmission.

Seasonal Malaria Vaccination

Radboudumc is coordinating an international consortium on delivery of seasonal malaria vaccination boosters (SMV Delivery) in Mali and Guinea. This project is funded through the Horizon Europe research funding scheme of the European Commission. Implementation studies in preselected districts in Guinea and Mali are used to respectively:

1. compare vaccination coverage and malaria incidence achieved with seasonal boosters (administered prior to malaria transmission season) vs. age-based boosters (administered regardless of season).
2. compare vaccination coverage and malaria incidence achieved with seasonal booster vaccinations provided through a door-to-door mass vaccination campaign vs. those provided at routine childhood vaccination centers.

Vaccine development

Plasmodium falciparum infection during pregnancy is a major health problem. It can lead to the development of placental malaria, which affects both, the pregnant women and their offspring. In 2023, over 12 million pregnant women were exposed to malaria, which is estimated to lead to up to 200,000 infant deaths each year and over 900,000 low birth weight infants. Placental malaria causes adverse pregnancy outcomes that range from subtle growth retardation to death of the mother and the child. In highly malaria-endemic regions, women in their first pregnancies are particularly vulnerable. The development of an effective and affordable vaccine would be critical to efficiently reduce the incidence and consequences of malaria in pregnancy.
Funded through the Horizon Europe research funding scheme of the European Commission, the ADVANCE-VAC4PM project aims at advancing development of two vaccines to prevent placental malaria.
A multicenter Phase 1 trial of the ADVANCE-VAC4PM vaccines will take place at the Radboudumc in The Netherlands and at the Groupe de Recherche Action en Santé (GRAS) in Burkina Faso.

Vaccine against Nipah virus

Nipah virus is a zoonotic disease that can spread to humans through fruit bats, pigs, contaminated food, and direct human-to-human contact. Infection with Nipah virus causes disease with a very high mortality rate. Currently there are no treatments or vaccines available.
Funded through the Horizon Europe research funding scheme of the European Commission, the VICI project aims at discovering and developing a Nipah virus vaccine, including clinical testing of the lead candidate. Radboudumc will conduct the first in human testing of the lead candidate in The Netherlands. Together with the Indian (PSG Institute of Medical Sciences & Research) and Gabonese (Centre de Recherche Médicales de Lambaréné) consortium partners, Radboudumc will be involved in developing a strategy for clinical testing of Nipah virus vaccines in endemic countries.

Pan-filovirus vaccine development

Funded through the Coalition for Epidemic Preparedness Innovations (CEPI), this project aims at developing a vaccine that provides protection against three of the deadliest filovirus diseases: Ebola-Sudan, Ebola-Zaïre and Marburg virus disease. An international consortium works on vaccine antigen identification and production. After preclinical testing, Radboudumc and Centre de Recherche Médicales de Lambaréné (CERMEL, Gabon) will test the panFiloVaxRR-vaccines for the first time in humans and vulnerable groups using innovative study designs that accelerate development towards use in future epidemics.