Oregon researchers identify parasite targets for universal malaria vaccine

Oregon Health & Science University researchers identified parasite targets on July 1 that could point toward a universal malaria vaccine, a finding that could reshape how the disease is prevented in places where repeated vaccination is hard to sustain. The work, published in Nature, focuses on telltale fragments of the malaria-causing parasite that the human immune system can recognize during the liver stage, before symptoms begin.

The team found a key bottleneck and vulnerability common to malaria species in that early stage. The fragments were shared by parasites from South America and Africa, and they were presented by HLA-E, an immune component nearly identical in every human.

The strategy is also different from the malaria vaccines already in use. Current licensed vaccines, RTS,S/AS01 and R21/Matrix-M, rely on conventional vaccine principles and are aimed at children in malaria-endemic areas, with the World Health Organization prioritizing moderate and high transmission settings. WHO updated its recommendation in October 2023 and reiterated it in a May 2024 position paper. As of Nov. 13, 2024, 15 countries had introduced malaria vaccination.

Brandon Wilder, who is leading the work at OHSU, said the parasite can grow in the liver for about a week and then generate roughly 50,000 parasites from a single hepatocyte. For a T cell-based vaccine, the liver is a target because T cells can identify and destroy infected cells rather than only targeting circulating pathogens. Researchers are now testing the first human vaccine candidates based on the findings in an animal model, using a minimally invasive biopsy technique developed by veterinary surgeons at the Oregon National Primate Research Center to check whether the immune system recognizes the fragments in the liver.

The World Health Organization estimated 282 million malaria cases and 610,000 deaths worldwide in 2024, with about 95% of deaths in the African Region and a heavy toll on children under 5. WHO estimated 263 million cases and 597,000 deaths in 2023, and the Centers for Disease Control and Prevention dates malaria vaccine development to the 1960s. CDC data show RTS,S cut clinical and severe malaria by about one-third in 5- to 17-month-old children over four years when given as a three-dose series plus a booster.