Human Challenge Center
Testing Malaria Vaccines and Prophylaxis
Located within Seattle Children’s Research Institute, the Malaria Human Challenge Center (HCC) is a unique, specialized facility designed to infect or “challenge” adult, healthy human volunteers with the malaria parasite under tightly controlled conditions. The primary goal of the HCC is to rapidly assess preliminary safety and efficacy of malaria vaccine candidates, including genetically attenuated whole parasite vaccines, allowing more rapid development of appropriate vaccine candidates.
The HCC is one of only a handful of facilities of its kind in the world where humans are inoculated with malaria sporozoites via mosquito bite under a meticulously regulated and controlled process. Both the manufacture of malaria-infected mosquitoes and delivery of the sporozoites to healthy individuals under a controlled human malaria infection (CHMI) occur within the HCC.
The HCC supports and fosters joint clinical trials for malaria vaccine development by establishing and maintaining key partnerships in the community to diversify capabilities, ensure sustainability and increase capacity. Overall, the HCC and its collaborators have conducted over 60 CHMI challenges in healthy adults, with more than 85 additional infectious mosquito-borne administrations of Plasmodium falciparum to healthy adults under experimental conditions.
Malaria remains a significant health problem, with an estimated 214 million cases worldwide in 2015 leading to an estimated 438,000 deaths, the vast majority of which were children under 5 years of age. Emerging parasite resistance to antimalarial medicines and mosquito resistance to insecticides could potentially trigger a rise in global malaria mortality. A highly effective vaccine is urgently needed to reduce the morbidity and mortality of this disease, particularly in children. As such, Seattle Children’s Research Institute is committed to this significant contribution toward accelerating malaria vaccine research in the Seattle area.
Frequently Asked Questions
Safety is our top priority
The Malaria Human Challenge Center (HCC) is a facility established by Seattle Children’s Research Institute to test experimental malaria vaccines and drugs in human clinical trials. This is one of only four centers in the world capable of testing new experimental malaria vaccines or drugs in humans by the Controlled Human Malaria Infection (CHMI) model, whereby participants are “challenged” with malaria under controlled conditions receiving the bites of malaria-infected mosquitos. This challenge will test how well an experimental vaccine or drug works against malaria.
If you're interested in possibily participating in a study, please visit SeattleMalaria.org.
Yes. Other centers in England and the Netherlands and at the Walter Reed Army Institute of Research (WRAIR) in Bethesda, Maryland, have been conducting human challenge trials for decades, but there is mutual recognition that expansion of the global capacity for conducting these types of trials is urgently required in order to bring new solutions to the world.
To establish the HCC and the human malaria challenge model at Seattle Children’s Research Institute, we worked very closely with our colleagues at WRAIR. WRAIR has been conducting challenge trials for decades with an outstanding safety record and expert knowledge base. WRAIR scientists have shared their expertise and provided the initial starting materials to produce the mosquitoes and malaria parasites for use in our trials at the HCC. Currently, the Center for Mosquito Production and Malaria Infection Research (CeMPMIR), under the direction of Dr. Stefan Kappe, produces malaria-infected mosquitoes used for the human challenge trials under current Good Manufacturing Practice (cGMP) regulations.
The clinical trials utilize a joint collaborative approach whereby the HCC provides infected mosquitoes and facilitates the administration of the challenge product. Many clinical trials are led by principal investigator Dr. James G. Kublin, who has extensive expertise in infectious disease, including malaria and HIV. The rest of our team includes Dr. Sean C. Murphy, HCC medical director, who has additional expertise in detection of malaria using qRT-PCR, and Dr. Ashley Vaughan, director of research, who is focused on understanding the complex biology of the malaria parasite and the immune responses to infection. Vaughan has also developed a Genetically Attenuated Parasite (GAP) vaccine candidate that recently completed safety trials.
The HCC and Seattle MCTC partner with local clinical research sites to conduct trials. These sites include Fred Hutch’s Vaccine Trial Unit, Kaiser Permanente Research Institute, Malaria Vaccine Initiative (MVI) and the University of Washington’s Virology Research Clinic (VRC).
The model of “challenging” humans in malaria vaccine trials is a well-established method that has been the mainstay of malaria vaccine and drug evaluation for decades. The type of malaria that volunteers are challenged with is a laboratory-raised strain under strictly controlled conditions (GMP) that is easy to diagnose and treat because it is very responsive to conventional malaria drugs. Other centers have conducted trials of this nature for decades with an extensive safety record. Participants challenged with malaria may develop flu-like symptoms with infection, but will be treated at the first sign of infection in the blood.
Safety is of the utmost importance in the design of our facilities and the conduct of malaria clinical trials. The HCC provides the highest level of care to ensure the safety of volunteers. We worked closely with our colleagues at the Walter Reed Army Institute of Research (WRAIR) in establishing the challenge center to harness their significant expertise in conducting these types of studies. WRAIR is home to the only other U.S. facility conducting malaria challenge trials and they have an outstanding safety record over the last two decades. WRAIR scientists have shared their knowledge with Seattle Children’s Research Institute scientists and have provided the starting materials to establish the mosquitoes and malaria parasites used in our trials.
The laboratory-raised strains of malaria used in these trials are well understood by our scientists and very responsive to common malaria treatments. These malaria parasites are tested to ensure that they can be killed by the standard FDA-approved medications used to treat malaria infection. They have been used in malaria clinical trials of this kind many times without causing severe illness in volunteers. Volunteers are closely monitored to ensure safety throughout the trial and are treated with antimalarial medication at the first sign of malaria infection in the blood.
All malaria clinical trial proposals are reviewed and approved by an independent institutional review board (IRB), whose primary purpose is to assure the protection of the rights, safety and welfare of human subjects. While not officially approved by the U.S. Food and Drug Administration (FDA), all studies of investigational drug and biologics must also be reviewed by the FDA for safety before they can be initiated at a center such as ours.