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https://hdl.handle.net/2440/88605
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Type: | Journal article |
Title: | Quantifying the importance of MSP1-19 as a target of growth-inhibitory and protective antibodies against Plasmodium falciparum in humans |
Author: | Wilson, D. Fowkes, F. Gilson, P. Elliott, S. Tavul, L. Michon, P. Dabod, E. Siba, P. Mueller, I. Crabb, B. Beeson, J. |
Citation: | PLoS One, 2011; 6(11):e27705-1-e27705-14 |
Publisher: | Public Library of Science |
Issue Date: | 2011 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Snounou, G. |
Statement of Responsibility: | 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 |
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. |
Keywords: | Animals Humans Plasmodium falciparum Parasitemia Malaria Recurrence Merozoite Surface Protein 1 Antibodies, Protozoan Vaccination Antibody Specificity Molecular Weight Adolescent Child Child, Preschool Adaptive Immunity |
Rights: | © 2011 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. |
DOI: | 10.1371/journal.pone.0027705 |
Grant ID: | ARC |
Published version: | http://dx.doi.org/10.1371/journal.pone.0027705 |
Appears in Collections: | Aurora harvest 2 Microbiology and Immunology publications |
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