A new way to study the immune system inside the liver is helping scientists with the Oregon National Primate Research Center at Oregon Health & Science Univesrity, explore a promising path toward a universal malaria vaccine by identifying how T cells may recognize shared targets across diverse malaria parasites. Malaria, a disease caused by parasites carried by mosquitoes, affects hundreds of millions of people annually and is the biggest single cause of childhood death worldwide.
Veterinary surgeons at the ONPRC developed a minimally invasive biopsy technique in nonhuman primates that allowed scientists to study immune responses in the liver and answer a key question about the vaccine targets. The findings are part of a study published in Nature by ONPRC researchers at Oregon Health & Science University and collaborators around the world.
Why a Malaria Vaccine Could Target the Liver
After a person is infected, malaria parasites travel first to the liver, where they develop before moving into the blood and infecting red blood cells. For a vaccine designed to stop malaria at this early stage, scientists need an immune response capable of recognizing the parasite in the liver.
However, malaria is a particularly difficult target for vaccines because the parasites that cause it are highly diverse. Researchers have been looking for pieces of the parasite that stay consistent across that diversity, giving the immune system a common target to recognize.
By studying blood samples from people with malaria in South America, collaborators identified protein fragments that remained remarkably similar across different malaria parasites, including species found in Africa. Some were also presented to T cells through HLA-E, an immune molecule that varies very little from person to person.
Together, those characteristics made the protein fragments potential targets for a universal malaria vaccine designed to provide broad protection against malaria.
A T Cell-Based Approach to Malaria Vaccination
Finding the protein fragments in human samples was an important first step. The ONPRC research is helping scientists investigate a new approach to malaria vaccination that harnesses CD8+ T cells, a type of white blood cell that helps the immune system recognize and eliminate infected cells. These T cells can recognize telltale protein fragments from viruses, bacteria or, in the case of malaria, parasites.
With the minimally invasive biopsy technique developed by ONPRC researchers, scientists could determine whether T cells could recognize these targets in the liver, where stopping the parasite early could make a meaningful difference. Researchers found that T cells in nonhuman primates recognized several of the newly identified malaria antigens in both the blood and liver following infection or immunization.
Connecting Discovery to Vaccine Development
The study brought together complementary areas of expertise. Human blood samples helped identify promising immune targets. Scientists at OHSU’s Vaccine and Gene Therapy Institute and collaborating institutions explored their potential for vaccination. ONPRC’s veterinary and nonhuman primate research expertise gave the team a way to investigate whether those targets could also be recognized inside the liver.
Researchers are now testing initial vaccine candidates based on the findings in the animal model. Their long-term goal is a T cell-based vaccine capable of protecting against the wide diversity of malaria parasites and potentially providing protection for years or even decades. While additional research is needed, the findings provide a potential path toward developing a malaria vaccine that offers broader and longer-lasting protection.
