Researchers at Oregon Health & Science University (OHSU) have achieved a significant breakthrough in malaria vaccine development, demonstrating 75-80% effectiveness in eliminating the parasite in rhesus macaques at the university's primate research center.
The innovative vaccine approach uses cytomegalovirus (CMV) as a delivery platform, potentially offering lifelong protection against a disease that infected 216 million people worldwide in 2016, resulting in 445,000 deaths, primarily in Africa.
"The problem with most vaccines is that their effectiveness is often short-lived," said the study's lead author, Klaus Früh, Ph.D., of OHSU's Vaccine & Gene Therapy Institute and professor of molecular and cellular biosciences. "Our cytomegalovirus-based vaccine platform can create and keep immunity for life. With further research and development, it could offer a lifetime of protection against malaria."
How the Vaccine Works
Unlike traditional vaccines that primarily generate antibody responses, OHSU's approach uses a weakened form of CMV—a common herpes virus that infects most people without causing disease—as a vehicle to deliver malaria parasite proteins into the body.
The engineered CMV vaccine prompts the immune system to produce specialized memory T-cells that can seek out and destroy cells infected with the malaria parasite. This approach is particularly promising because these T-cells concentrate in the liver, where the Plasmodium parasite initially hides after infection before entering the bloodstream.
"This is proof of concept," Früh told The Lund Report. "I would like to see better protection. We had one animal in one group that didn't develop any parasites. We need to increase that number."
The research team developed two versions of their CMV-based malaria vaccine using four different proteins from the Plasmodium parasite. When tested in 16 rhesus macaques, the vaccines delayed the parasite's appearance in the blood by eliminating 75-80% of parasites from the liver. Importantly, the vaccinated primates maintained immunity against malaria a year later.
Advantages Over Existing Approaches
The current leading malaria vaccine, RTS,S (brand name Mosquirix), which is being used in routine vaccination programs in three African countries, has shown limited effectiveness. Its protection rate drops from 39% in children four years after administration to just 4.4% after seven years.
By contrast, the CMV-based platform developed at OHSU could potentially provide lifelong protection, addressing one of the major challenges in malaria vaccine development.
The same platform technology is already being used in vaccines under development for HIV and tuberculosis. Vir Biotechnology, Inc., which has licensed the CMV vaccine platform, plans to conduct human clinical trials for a CMV-based HIV vaccine within the next 12-18 months.
Next Steps in Development
Despite the promising results, the vaccine is not yet ready for human trials. The research team aims to improve its effectiveness to achieve 100% protection against malaria by evaluating 15 different Plasmodium-made proteins for inclusion in the vaccine.
They are also exploring the possibility of combining their CMV-based vaccine with other experimental vaccines or the existing RTS,S vaccine to enhance overall protection.
"Though the vaccine is not ready for prime time yet, it offers hope for an eventual vaccine that would protect people against the disease, which is rampant in developing countries," Früh noted.
The Malaria Challenge
Malaria remains one of the world's most persistent public health challenges. When a malaria-infected mosquito bites a human, the Plasmodium parasite enters the bloodstream and quickly travels to the liver, where it reproduces before being released back into the blood. The parasite then infects red blood cells, causing them to burst, which leads to fever and other symptoms.
If not promptly treated, malaria can cause kidney failure, seizures, coma, and death. The disease disproportionately affects developing countries, with Africa bearing the highest burden.
The OHSU vaccine aims to halt the parasite in the liver before it can cause damage, potentially providing a transformative tool in global efforts to combat this deadly disease.
The study, which was five years in the making, was published in the journal PLOS ONE. It represents a collaboration between OHSU, the Naval Medical Research Center, National Institutes of Health, and Fred Hutchinson Cancer Research Center, with support from the Military Infectious Diseases Research Program and the National Institutes of Health.
