From human antibody structure and function towards the design of a novel Plasmodium falciparum circumsporozoite protein malaria vaccine

Malaria is a life-threatening vector-borne disease caused by Plasmodium parasites that infect millions of people in endemic areas every year. The most advanced malaria vaccine candidate RTS,S targets the immune response against circumsporozoite protein of Plasmodium falciparum (PfCSP), the most deadly Plasmodium species in humans. PfCSP plays a fundamental role in parasite development as well as the establishment of the infection and is a molecular target of protective antibodies. However, RTS,S shows overall low efficacy and insufficient long-term protection. Therefore, a major goal in the development of an improved PfCSP-based vaccine remains the reliable and stable induction of protective and ideally sterilizing antibody titers. The molecular and functional characterization of human anti-PfCSP antibody responses paves the way for the rational design of novel immunogens for the development of an improved next-generation PfCSP malaria vaccine.