title: Quantifying the importance of MSP1-19 as a target of growth-inhibitory and protective antibodies against Plasmodium falciparum in humans.
abstract: BACKGROUND
  Antibodies targeting blood stage antigens are important in protection against malaria, but the key targets and mechanisms of immunity are not well understood. Merozoite surface protein 1 (MSP1) is an abundant and essential protein. The C-terminal 19 kDa region (MSP1-19) is regarded as a promising vaccine candidate and may also be an important target of immunity.
  
  
  RESULTS
  Growth inhibitory antibodies against asexual-stage parasites and IgG to recombinant MSP1-19 were measured in plasma samples from a longitudinal cohort of 206 children in Papua New Guinea. Differential inhibition by samples of mutant P. falciparum lines that expressed either the P. falciparum or P. chabaudi form of MSP1-19 were used to quantify MSP1-19 specific growth-inhibitory antibodies. The great majority of children had detectable IgG to MSP1-19, and high levels of IgG were significantly associated with a reduced risk of symptomatic P. falciparum malaria during the 6-month follow-up period. However, there was little evidence of PfMSP1-19 specific growth inhibition by plasma samples from children. Similar results were found when testing non-dialysed or dialysed plasma, or purified antibodies, or when measuring growth inhibition in flow cytometry or microscopy-based assays. Rabbit antisera generated by immunization with recombinant MSP1-19 demonstrated strong MSP1-19 specific growth-inhibitory activity, which appeared to be due to much higher antibody levels than human samples; antibody avidity was similar between rabbit antisera and human plasma.
  
  
  CONCLUSIONS
  These data suggest that MSP1-19 is not a major target of growth inhibitory antibodies and that the protective effects of antibodies to MSP1-19 are not due to growth inhibitory activity, but may instead be mediated by other mechanisms. Alternatively, antibodies to MSP1-19 may act as a marker of protective immunity.
authors: The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
authors: Danny W
authors: DW
authors: Wilson
authors: Freya J I
authors: FJ
authors: Fowkes
authors: Paul R
authors: PR
authors: Gilson
authors: Salenna R
authors: SR
authors: Elliott
authors: Livingstone
authors: L
authors: Tavul
authors: Pascal
authors: P
authors: Michon
authors: Elija
authors: E
authors: Dabod
authors: Peter M
authors: PM
authors: Siba
authors: Ivo
authors: I
authors: Mueller
authors: Brendan S
authors: BS
authors: Crabb
authors: James G
authors: JG
authors: Beeson
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000293:Adolescent; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity; D002648:Child; D002675:Child, Preschool; D006801:Humans; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000737:chemistry* / Q000276:immunology*; D008970:Molecular Weight; D018512:Parasitemia / Q000276:immunology / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology* / Q000472:pathogenicity; D012008:Recurrence; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1