title: Designing malaria vaccines to circumvent antigen variability.
abstract: Prospects for malaria eradication will be greatly enhanced by an effective vaccine, but parasite genetic diversity poses a major impediment to malaria vaccine efficacy. In recent pre-clinical and field trials, vaccines based on polymorphic Plasmodium falciparum antigens have shown efficacy only against homologous strains, raising the specter of allele-specific immunity such as that which plagues vaccines against influenza and HIV. The most advanced malaria vaccine, RTS,S, targets relatively conserved epitopes on the P. falciparum circumsporozoite protein. After more than 40 years of development and testing, RTS,S, has shown significant but modest efficacy against clinical malaria in phase 2 and 3 trials. Ongoing phase 2 studies of an irradiated sporozoite vaccine will ascertain whether the full protection against homologous experimental malaria challenge conferred by high doses of a whole organism vaccine can provide protection against diverse strains in the field. Here we review and evaluate approaches being taken to design broadly cross-protective malaria vaccines.
authors.affiliation: Institute for Global Health and Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, MD, USA; Malaria Research and Training Center, University of Sciences, Techniques and Technology, Bamako, Mali. Electronic address: aouattara@medicine.umaryland.edu.
authors.forename: Amed
authors.initials: A
authors.lastname: Ouattara
authors.affiliation: Division of Population Health and Immunity, Walter and Eliza Hall Institute for Medical Research, Parkville, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia. Electronic address: barry@wehi.edu.au.
authors.forename: Alyssa E
authors.initials: AE
authors.lastname: Barry
authors.affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, USA. Electronic address: sheetij.dutta.civ@mail.mil.
authors.forename: Sheetij
authors.initials: S
authors.lastname: Dutta
authors.affiliation: The Biomedical Primate Research Center, Rijswijk, Netherlands. Electronic address: remarque@bprc.nl.
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: Remarque
authors.affiliation: Burnet Institute, Melbourne, Victoria, Australia; Department of Microbiology, Monash University, Victoria, Australia. Electronic address: beeson@burnet.edu.au.
authors.forename: James G
authors.initials: JG
authors.lastname: Beeson
authors.affiliation: Institute for Global Health and Howard Hughes Medical Institute, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: cplowe@medicine.umaryland.edu.
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Plowe
mesh_terms: D000940:Antigenic Variation; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D056738:Cross Protection; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology; D010963:Plasmodium falciparum / Q000737:chemistry / Q000235:genetics; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D034101:Sporozoites / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014613:Vaccines, Attenuated; D022223:Vaccines, Subunit
keywords: Allele-specific efficacy; Cross-protection; Diversity; Heterologous; Malaria; Vaccine