The blood stage of the malaria parasite life cycle is responsible for all the clinical symptoms of malaria. During the blood stage, Plasmodium merozoites invade and multiply within host red blood cells (RBCs). Here, we review the progress made, challenges faced, and new strategies available for the development of blood stage malaria vaccines. We discuss our current understanding of immune responses against blood stages and the status of clinical development of various blood stage malaria vaccine candidates. We then discuss possible paths forward to develop effective blood stage malaria vaccines. This includes a discussion of protective immune mechanisms that can be elicited to target blood stage parasites, novel delivery systems, immunoassays and animal models to optimize vaccine candidates in preclinical studies, and use of challenge models to get an early readout of vaccine efficacy.
Keywords: Blood stage vaccines; Immunity to malaria; Malaria; Malaria vaccines; Vaccine development.