Grant: CIHR Fellowship

Efforts to generate an effective vaccine against malaria have been ongoing for more than a century. Towards this goal, the World Health Organization has set a minimum target of 75% vaccine efficacy (VE) for novel vaccine candidates. In 2021, a vaccine candidate developed at the Jenner Institute known as R21/Matrix-M exceeded that goal with a VE of 80% in a clinical trial conducted in African children. This vaccine candidate has now been recommended by the WHO for use in children in countries where malaria is endemic. An estimated 50 million people travel to malaria-endemic regions annually, yet an efficacious vaccination regimen in malaria-naïve adults has not been determined. Current strategies for mitigation rely on prophylaxis with antimalarial medications. Prophylaxis regimens are expensive and failure-prone with significant side-effects limiting their prescription in pregnancy, children, and in those with common neuropsychiatric disorders such as depression. Vaccination with R21/Matrix-M is not only safe in children, but also avoids the side-effects common to antimalarial medications. Furthermore, the vaccine is inexpensive ($4 USD/dose) supporting its implementation as a traveler's vaccine if shown to be effective in this population. We will perform a combined safety and efficacy trial of R21/Matrix-M in healthy malaria-naïve adult volunteers. VE will be assessed by controlled human infection via infectious mosquito bites conducted at Imperial College London. Clinical and immunologic analyses will be performed at the Jenner Institute in Oxford, UK. Significance: We will identify an effective dosing schedule for vaccination of healthy malaria-naïve adults with R21/Matrix-M. Our results will build towards a vaccine that protects at-risk populations living in non-endemic regions against malaria disease. Additionally, this postdoctoral training will provide me the experience needed to investigate future vaccines in my own independent research program.