title: Cross-species immunity following immunization with a circumsporozoite protein-based vaccine for malaria.
abstract: Malaria continues to be a major public health concern, and there are concerted efforts to eliminate it. The quest for a vaccine remains a top priority, and vaccines based on the circumsporozoite protein (CSP) are among the lead candidates, with the RTS,S vaccine currently undergoing phase 3 testing in Africa. Previous studies have reported anti-CSP antibody-mediated enhancement of in vitro invasion of homologous sporozoites. This effect has been shown to be concentration dependent; high-level antibodies are inhibitory, whereas low-level antibodies lead to enhancement of invasion. Nondominant shared epitopes may lead to the generation of low titers of cross-reactive antibodies that may prove to be detrimental. We report cross-species recognition of Plasmodium falciparum and Plasmodium berghei sporozoites by anti-Plasmodium vivax CSP serum samples. In addition, we report that vaccination of mice with VMP001, a P. vivax CSP vaccine candidate, reduces, not enhances, P. berghei infection in mice.
authors.affiliation: Malaria Vaccine Branch, United States Military Malaria Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910, USA. anjali.yadava@us.army.mil
authors.forename: Anjali
authors.initials: A
authors.lastname: Yadava
authors.forename: Saule
authors.initials: S
authors.lastname: Nurmukhambetova
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Pichugin
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lumsden
mesh_terms: D000349:Africa; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D056738:Cross Protection; D000939:Epitopes / Q000276:immunology; D005260:Female; D007114:Immunization; D008288:Malaria / Q000276:immunology* / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology; D010966:Plasmodium vivax / Q000276:immunology; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D034101:Sporozoites / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan