[Show abstract][Hide abstract] ABSTRACT: Summary of PfMSP1-19 specific inhibition levels reported in different studies.aS = serum. P = plasma.bM = microscopy based assay. F = flow cytometry based assay. H = Hypoxanthine uptake assay.c Microscopy based assays for Bagabag Island and Madang samples were completed using the D10 wildtype line. Hypoxanthine uptake based assays for Bagabag Island and Madang samples were completed using the transfected D10-PfM3′ line .d Interpretation from Figures 2C and 2D and information in text.d Inhibition minimum at 6 months (16% n = 24) maximum at 24–30 months (29%, n = 19).e Inhibition range for 9 of 20 returned travelers considered to have significant PfMSP1-19 specific inhibition. Data for remaining 11 travelers not reported.f Interpretation from Figures 2B and 3. Spaghetti plots of timepoints for all samples available in supplementary file 4 of the manuscript.g Calculated median for all 137 samples listed in table 1 of the manuscript. Calculated medians for the 3 timepoints are t = 0 (9%, n = 65), t = 1 (10%, n = 37), t = 28 (−14%, n = 35). NR = not reported in manuscript.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.