Accelerating the development of next generation malaria vaccines through development of innovative trial designs in malaria-endemic areas.

Malaria parasites are still slipping past the only licensed vaccine, which only targets the early liver stage of infection. This project aims to speed up development of a more effective vaccine that attacks the parasite at multiple points in its life cycle—in the liver, in the blood, and during transmission to mosquitoes. The core problem is that researchers lack efficient ways to test which of hundreds of potential vaccine targets actually work in people who have already been exposed to malaria. The team will use controlled human malaria infection (CHMI) in semi-immune adults to solve this. They will characterise immunity to malaria using more than 100 antigens in thousands of semi-immune adults, then select 200 with different immunological profiles for CHMI studies. They will also vary the parasite dose and use low doses of anti-malarial drugs to produce gametocytes—the sexual stage that infects mosquitoes—and test whether vaccinated people can still transmit the parasite. If successful, this approach could dramatically shorten the timeline for developing a multi-stage malaria vaccine. Instead of waiting years for large field trials to fail, researchers would have a rapid, controlled way to prioritise the most promising antigens and discard weak candidates early. A more effective vaccine could reduce the hundreds of thousands of child deaths malaria still causes each year.