Abstract
The complex Plasmodium life cycle offers different vaccine approaches with distinct parasitological and clinical effects. The approaches and their rationales were established decades ago: vaccines targeting pre-erythrocytic (sporozoite and liver-stage) parasites prevent infection, those to blood-stage parasites reduce disease, and those to sexual-stage parasites or mosquito vector reduce transmission and eliminate malaria through herd immunity. The pre-erythrocytic RTS,S vaccine (Mosquirix, GlaskoSmithKline (GSK)), recommended by WHO in 2021, reduces clinical malaria in children. Knowledge of parasite biology, host-parasite interactions, and immune mechanisms is informing new concepts to improve on RTS,S and to target other parasite stages. This review emphasizes vaccine approaches and candidates currently in the clinic or likely to enter clinical testing soon.