Quantifying the importance of MSP1-19 as a target of growth-inhibitory and protective antibodies against Plasmodium falciparum in humans

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 va...

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Bibliographic Details
Published in:PloS one 2011-11, Vol.6 (11), p.e27705-e27705
Main Authors: Wilson, Danny W, Fowkes, Freya J I, Gilson, Paul R, Elliott, Salenna R, Tavul, Livingstone, Michon, Pascal, Dabod, Elija, Siba, Peter M, Mueller, Ivo, Crabb, Brendan S, Beeson, James G
Format: Article
Language:English
Subjects:
Adaptive Immunity - immunology
Adolescent
Animals
Antibodies
Antibodies, Protozoan - blood
Antibodies, Protozoan - immunology
Antibody Specificity
Antigens
Antisera
Avidity
Biology
Blood plasma
Child
Child, Preschool
Children
Cytometry
Erythrocytes
Flow cytometry
Growth
Health risks
Humans
Immunity
Immunization
Immunoglobulin G
Immunoglobulins
Inhibition
Malaria
Malaria - immunology
Malaria - prevention & control
Medical research
Medicine
Merozoite surface protein 1
Merozoite Surface Protein 1 - chemistry
Merozoite Surface Protein 1 - immunology
Microscopy
Molecular Weight
Morbidity
Parasitemia - immunology
Parasitemia - prevention & control
Parasites
Plasmodium falciparum
Plasmodium falciparum - growth & development
Plasmodium falciparum - immunology
Plasmodium falciparum - pathogenicity
Proteins
Public health
Recurrence
Risk reduction
Studies
Vaccination
Vaccines
Vector-borne diseases
Womens health
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0027705