Quantifying the Importance of MSP1-19 as a Target of Growth-Inhibitory and Protective Antibodies against Plasmodium falciparum in Humans

Danny W Wilson, Freya J I Fowkes, Paul R. Gilson, Salenna R Elliott, Livingstone Tavul, Pascal Michon, Elija Dabod, Peter M. Siba, Ivo Mueller, Brendan S. Crabb, James G. Beeson

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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. Methodology/Findings: 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/Significance: 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.

Original languageEnglish
Article numbere27705
Number of pages14
JournalPLoS ONE
Issue number11
Publication statusPublished - 15 Nov 2011


  • enzyme-linked immunoassays
  • antibodies
  • malaria
  • plasmodium
  • parasitemia
  • flow cytometry
  • malarial parasites
  • immune serum

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