title: The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment.
abstract: Rodent malaria species Plasmodium yoelii and P. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. However, increasing data suggest the P. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. Here we confirm a failure to protect against P. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. No subunit vaccine approach showed efficacy in mice following immunization and challenge with the wild-type P. berghei strains ANKA or NK65, or against a chimeric parasite line encoding a merozoite antigen from P. falciparum. Protection was not improved in knockout mice lacking the inhibitory Fc receptor CD32b, nor against a Δsmac P. berghei parasite line with a non-sequestering phenotype. An improved understanding of the mechanisms responsible for protection, or failure of protection, against P. berghei merozoites could guide the development of an efficacious vaccine against P. falciparum.
authors.affiliation: The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK. goodmananna@hotmail.com
authors.forename: Anna L
authors.initials: AL
authors.lastname: Goodman
authors.forename: Emily K
authors.initials: EK
authors.lastname: Forbes
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Williams
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Douglas
authors.forename: Simone C
authors.initials: SC
authors.lastname: de Cassan
authors.forename: Karolis
authors.initials: K
authors.lastname: Bauza
authors.forename: Sumi
authors.initials: S
authors.lastname: Biswas
authors.forename: Matthew D J
authors.initials: MD
authors.lastname: Dicks
authors.forename: David
authors.initials: D
authors.lastname: Llewellyn
authors.forename: Anne C
authors.initials: AC
authors.lastname: Moore
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Janse
authors.forename: Blandine M
authors.initials: BM
authors.lastname: Franke-Fayard
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Pleass
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Draper
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology; D000962:Antimalarials / Q000276:immunology*; D002460:Cell Line; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007114:Immunization / Q000379:methods; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D052940:Merozoites / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010962:Plasmodium berghei / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D011817:Rabbits; D017452:Receptors, IgG / Q000276:immunology; D012377:Rodentia / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000962:Antimalarials; C080571:Fc gamma receptor IIB; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; D017452:Receptors, IgG; C455300:merozoite surface protein 9, Plasmodium