Malaria-ResearchAn 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 volunteersDuring 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.
What takes place during a controlled human malaria infection?Step 1: Medical examination
Volunteers will receive a comprehensive medical examination. A volunteer can only participate in the study if he or she is completely healthy.
Step 2: The malaria infection
A cage containing mosquitoes infected with Plasmodium falciparum parasites is placed onto the forearms of the volunteers. These mosquitoes are bred in the malaria unit of Radboud university medical center and have never been in the outside world. The malaria parasites are bred according to the highest quality standards and are susceptible to standard antimalarials.
Step 3: Close medical monitoring
Our clinical-researchers monitor the volunteers daily to see if they develop malaria. If the malaria infection was successful, this is always the case. A volunteer will develop malaria within a maximum of 21 days, but usually between the 7th and 11th day after exposure to the infected mosquitoes. For this reason, beginning on the 6th day after exposure, volunteers will be tested daily during which blood samples will be taken until the infection is detected.
Step 4: Malaria treatment
As soon as the malaria parasites appear in the blood, we will treat the volunteer with highly effective antimalarials. It is expected that the malaria infection will cause most volunteers to develop flu-like symptoms such as headaches, muscle pain, fatigue, and sometimes fever. These symptoms usually disappear within a few days. After this malaria treatment, the malaria parasites will disappear from the body entirely and there is no chance that the infection will return.
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.
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 has started in April 2019.
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.