Quantifying the Importance of MSP1-19 as a Target of Growth-Inhibitory and Protective Antibodies against Plasmodium falciparum in Humans
- Author(s)
- Wilson, DW; Fowkes, FJI; Gilson, PR; Elliott, SR; Tavul, L; Michon, P; Dabod, E; Siba, PM; Mueller, I; Crabb, BS; Beeson, JG;
- Details
- Publication Year 2011-11-15,Volume 6,Issue #11,Page e27705
- Journal Title
- PLOS ONE
- Publication Type
- Journal Article
- 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. 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.
- Publisher
- PUBLIC LIBRARY SCIENCE
- Keywords
- MEROZOITE SURFACE PROTEIN-1; NEW-GUINEAN CHILDREN; NATURALLY ACQUIRED ANTIBODIES; APICAL MEMBRANE ANTIGEN-1; GLUTAMATE-RICH PROTEIN; BLOOD-STAGE INFECTION; C-TERMINAL FRAGMENT; CLINICAL MALARIA; IN-VITRO; ERYTHROCYTE INVASION
- Research Division(s)
- Infection And Immunity
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0027705
- Open Access at Publisher's Site
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3217002/- Terms of Use/Rights Notice
- Copyright Wilson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creation Date: 2011-11-15 12:00:00