title: Cross-stage immunity for malaria vaccine development.
abstract: A vaccine against malaria is urgently needed for control and eventual eradication. Different approaches are pursued to induce either sterile immunity directed against pre-erythrocytic parasites or to mimic naturally acquired immunity by controlling blood-stage parasite densities and disease severity. Pre-erythrocytic and blood-stage malaria vaccines are often seen as opposing tactics, but it is likely that they have to be combined into a multi-stage malaria vaccine to be optimally safe and effective. Since many antigenic targets are shared between liver- and blood-stage parasites, malaria vaccines have the potential to elicit cross-stage protection with immune mechanisms against both stages complementing and enhancing each other. Here we discuss evidence from pre-erythrocytic and blood-stage subunit and whole parasite vaccination approaches that show that protection against malaria is not necessarily stage-specific. Parasites arresting at late liver-stages especially, can induce powerful blood-stage immunity, and similarly exposure to blood-stage parasites can afford pre-erythrocytic immunity. The incorporation of a blood-stage component into a multi-stage malaria vaccine would hence not only combat breakthrough infections in the blood should the pre-erythrocytic component fail to induce sterile protection, but would also actively enhance the pre-erythrocytic potency of this vaccine. We therefore advocate that future studies should concentrate on the identification of cross-stage protective malaria antigens, which can empower multi-stage malaria vaccine development.
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London, United Kingdom; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Wiebke.Nahrendorf@ed.ac.uk.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Nahrendorf
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Anja.Scholzen@radboudumc.nl.
authors.forename: Anja
authors.initials: A
authors.lastname: Scholzen
authors.affiliation: Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Robert.Sauerwein@radboudumc.nl.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: Mill Hill Laboratory, The Francis Crick Institute, London, United Kingdom. Electronic address: Jean.Langhorne@crick.ac.uk.
authors.forename: Jean
authors.initials: J
authors.lastname: Langhorne
mesh_terms: D000953:Antigens, Protozoan / Q000276:immunology*; D056738:Cross Protection; D004912:Erythrocytes / Q000469:parasitology; D008018:Life Cycle Stages / Q000276:immunology; D008099:Liver / Q000469:parasitology; D008288:Malaria / Q000276:immunology* / Q000469:parasitology; D017780:Malaria Vaccines / Q000276:immunology*; D010961:Plasmodium / Q000254:growth & development* / Q000276:immunology*; D014611:Vaccination
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines
keywords: Blood-stage; Cross-stage; Immunization; Malaria; Pre-erythrocytic; Vaccine