An effective vaccine is imperative in the fight against malaria. The Center for Clinical Malaria Studies has been performing research for more than fifteen years to contribute toward the development of such a vaccine.
Controlled human malaria infections in volunteers
During controlled human malaria infections (CHMI), we infect healthy volunteers with malaria by having them bitten by malaria-infected mosquitoes. Over the course of the infection, doctors and researchers are able to acquire information about the illness, which they can use to develop better treatment methods. In this way, the effectiveness of a new malaria vaccine can also be tested.
Human testing is necessary because the current animal testing models are not precise enough for human malaria. At the Center for Clinical Malaria Studies at Radboud university medical center, we have more than fifteen years of experience with experimental human malaria studies.
Malaria vaccine developmentThrough controlled human malaria infections in healthy volunteers, researchers can study the immune response to malaria. We use this knowledge to develop new, better malaria vaccines.
We research how the malaria parasite itself can be used as a vaccine by repeatedly infecting healthy volunteers with malaria while they take antimalarials. The antimalarials prevent the volunteers from becoming ill, but the immune system comes into contact with the parasite and learns how to destroy it. If these volunteers are bitten by mosquitoes with malaria again, they will no longer become sick even without the antimalarials.
Together with the Leiden University Medical Center and the American company Sanaria Inc., a weakened malaria parasite has been developed at Radboud university medical center, in which two genes have been removed. This “genetically modified” parasite stops developing early on, which, as expected, results in no symptoms occurring in the human subject, but it is still recognized by the immune system. In 2017, we will test if this parasite can be used as a vaccine.
Testing malaria vaccinesTesting of a potential vaccine must first be done extensively on laboratory animals. At a later stage, the vaccines will be tested on healthy volunteers. After a malaria vaccine is found to be safe in healthy volunteers, it will be tested whether the vaccine is effective in preventing malaria. Sometimes, this research is conducted among a group of volunteers in countries where malaria is very common, like in Africa. However, these types of studies are often difficult to set up and conduct in Africa. In order to advance the development of malaria vaccines, these types of studies can also be performed in countries where malaria does not occur naturally. This involves healthy volunteers receiving the new vaccine and being exposed to malaria under strictly controlled conditions in order to see whether the vaccine can effectively prevent malaria.
The Center for Clinical Malaria Studies (CCMS) of Radboud university medical center in Nijmegen is one of the few places in the world where the malaria vaccine can be tested on healthy volunteers. In the meantime, the CCMS has accumulated over fifteen years of experience in this area.
In the years to come, multiple studies with promising malaria vaccines will be performed at the CCMS.
At this moment we are conducting two malaria research studies.
TB31F study - research with a medicinal product
TB31F is an antibody which we believe may stop transmission (spreading) of malaria to a next person. TB31F has been tested in the laboratory and in animals but it has not been tested in humans before. In this study, TB31F will be tested in various dosages. The results of this research are important for the development of TB31F as a medicine to stop the spread of malaria. This study has started in Februay 2020 and will be completed in December 2020.
In this study we wish to investigate the Safety and protective efficacy of chemoprophylaxis and sporozoite immunization with Plasmodium falciparum NF135 against homologous and heterologous challenge infection in healthy volunteers in the Netherlands. This study will be completed early 2021.
CPS135 malaria study
with controlled human malaria infections
CHMI-Trans1 & CHMI-Trans2 study (2018)The primary aim of these projects was to develop a controlled human malaria infection transmission model (“CHMI-trans”) or ‘challenge model’ to evaluate the capacity of vaccines, biologics (monoclonal antibodies, or mAbs), and drugs to block malaria parasite transmission. CHMI-trans2 was a sequel on CHMI-trans1 for the optimization of the transmission model.
Outcome: A clinical protocol to measure transition of the malaria parasite from men to mosquito. The novel clinical model will allow testing of transmission-blocking interventions.
PbVac study (2017/2018)This study was focused on the safety and protective efficacy of genetically modified Plasmodium berghei (Pb(PfCS@UIS4)) malaria parasites in healthy volunteers. This multi-center study was performed in close collaboration with Erasmus MC.
Outcome: Immunization with PbVac is safe and well tolerated with induction of functional immune responses in in vitro assays. No complete protection was not observed, but there was significant delay in parasite patency after the controlled human malaria infection challenge.
GA1 study (2017/2018)The primary aim of this project was to determine the safety and tolerability of direct venous inoculation (DVI) of PfSPZ-GA1 in healthy volunteers. Secondary we aimed to investigate the short-term protective efficacy of PfSPZ-GA1 against Controlled Human Malaria Infection (CHMI) by mosquito bite. The GA1 study was a multi-center study with Leiden University Medical Center
Outcome: Immunisations with PfSPZ-GA1 are well tolerated and safe with modest induction of immune responses and modest protection after challenge. However, no definite conclusion can be drawn from this trial on the potential protective efficacy PfSPZ-GA1.