Unique Whole Parasite Malaria Vaccine Shows Promise During School of Medicine Clinical Trial
For the first time, a malaria vaccine that uses the entire malaria parasite has proven safe and shown promise to produce a strong immune response in a clinical trial, according to a new study co-authored by researchers at the Center for Vaccine Development (CVD) at the School of Medicine. The study may be an important step in the decades-long effort to develop an effective malaria vaccine.
Most experimental malaria vaccines consist of only one or at most a few proteins found in the parasite. Researchers found that the first whole parasite vaccine to be approved by the Food and Drug Administration for clinical trials could provide unprecedented immune responses against malaria when administered intravenously. The study was recently published online in the journal Science (www.sciencexpress.org).
“No vaccine has completely protected against malaria in a challenge trial, in which vaccinated volunteers are subjected to the bite of an infected mosquito to measure their immunity,” says Kirsten Lyke, MD, associate professor at the School of Medicine and a research scientist at CVD. “This vaccine showed strong promise. We hope that with further study it could help revolutionize the field and prevent death and illness from malaria worldwide, and be used to eliminate malaria from certain areas.”
Lyke collaborated on the study with fellow School of Medicine scientists including Matthew Laurens, MD, MPH, assistant professor, and Christopher Plowe, MD, professor and chief of the School’s malaria section. Robert Edelman, MD, clinical professor, also contributed to the paper. The group co-authored the study with colleagues from the Howard Hughes Medical Institute, the PATH Malaria Vaccine Initiative, the U.S. Military Malaria Vaccine Program, the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases, the Walter Reed Army Institute of Research, the biotechnology research firm Protein Potential LLC, and Sanaria, Inc., which developed and manufactured the vaccine.
Though malaria has been largely eliminated in much of the developed world, it is still a widespread threat in warm, tropical areas where infected mosquitoes thrive. Caused by a parasite transmitted through the bite of an infected mosquito, malaria kills about one million people annually worldwide. The condition can be treated with anti-parasite drugs, but it can be fatal for vulnerable patients who have no immunity to the disease. Children under the age of 5 succumb at high rates to the neurological and cardiac effects of malaria, particularly in Africa.
Researchers found that the whole parasite vaccine produced a partial protective response in the 80 volunteers who were immunized subcutaneously (under the skin) by traditional needle and syringe during the CVD trial. The response was significantly less than the 80 percent to 90 percent protective immunity the research team wants to achieve. Further study conducted by collaborating authors from the Vaccine Research Center found that administering the vaccine intravenously produced a very high level of immune response in animal subjects.
“Our hope is that we can optimize the delivery of this vaccine to prevent and eliminate malaria on a global level,” says Lyke, who is working with colleagues to design new studies to find the best way to administer the vaccine.
A whole parasite vaccine is believed to be more capable than a recombinant vaccine of broadly protecting people from the scores of varying strains of malaria, but whole parasite vaccines have seemed unattainable because of the many challenges of large scale production and preservation of whole parasites, which can only be produced by infecting mosquitoes with malaria-infected blood. Using mosquitoes raised in aseptic conditions, Sanaria, Inc., developed a unique production and cryopreservation process that allows the parasite to be frozen, shipped to remote locations, and safely thawed.
“The University of Maryland School of Medicine and its Center for Vaccine Development have a world-leading malaria research program with a prominent global presence, including in remote areas of Africa where malaria rates are at their worst,” says E. Albert Reece, MD, PhD, MBA, vice president for medical affairs at the University, and the John Z. and Akiko K. Bowers Distinguished Professor and dean of the School of Medicine. “This research is the culmination of decades of study in this field, and brings hope to the millions of people worldwide who face the daily threat of malaria.”
As a Phase I trial, the study’s focus was to establish that the vaccine is safe and well tolerated. The results have guided the design of the next study, a Phase II clinical trial in which scientists will administer the vaccine intravenously to human volunteers and measure immunity to determine the vaccine’s effectiveness.
“Does this vaccine have enough immunological firepower to protect against all the different strains [of malaria] circulating in the field?” asks Plowe. “If the whole parasite doesn’t work, I don’t know what will. This is the best chance we’ve got.”