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Acquired Antibodies to Merozoite Antigens in Children from Uganda with Uncomplicated or Severe Plasmodium falciparum Malaria

Ismail, H. A.; Ribacke, U.; Reiling, L.; Normark, J.; Egwang, T.; Kironde, F.; Beeson, J. G.; Wahlgren, M. and Persson, Kristina LU (2013) In Clinical and Vaccine Immunology 20(8). p.1170-1180
Abstract
Malaria can present itself as an uncomplicated or severe disease. We have here studied the quantity and quality of antibody responses against merozoite antigens, as well as multiplicity of infection (MOI), in children from Uganda. We found higher levels of IgG antibodies toward erythrocyte-binding antigen EBA181, MSP2 of Plasmodium falciparum 3D7 and FC27 (MSP2-3D7/FC27), and apical membrane antigen 1 (AMA1) in patients with uncomplicated malaria by enzyme-linked immunosorbent assay (ELISA) but no differences against EBA140, EBA175, MSP1, and reticulocyte-binding protein homologues Rh2 and Rh4 or for IgM against MSP2-3D7/FC27. Patients with uncomplicated malaria were also shown to have higher antibody affinities for AMA1 by surface plasmon... (More)
Malaria can present itself as an uncomplicated or severe disease. We have here studied the quantity and quality of antibody responses against merozoite antigens, as well as multiplicity of infection (MOI), in children from Uganda. We found higher levels of IgG antibodies toward erythrocyte-binding antigen EBA181, MSP2 of Plasmodium falciparum 3D7 and FC27 (MSP2-3D7/FC27), and apical membrane antigen 1 (AMA1) in patients with uncomplicated malaria by enzyme-linked immunosorbent assay (ELISA) but no differences against EBA140, EBA175, MSP1, and reticulocyte-binding protein homologues Rh2 and Rh4 or for IgM against MSP2-3D7/FC27. Patients with uncomplicated malaria were also shown to have higher antibody affinities for AMA1 by surface plasmon resonance (SPR). Decreased invasion of two clinical P. falciparum isolates in the presence of patient plasma correlated with lower initial parasitemia in the patients, in contrast to comparisons of parasitemia to ELISA values or antibody affinities, which did not show any correlations. Analysis of the heterogeneity of the infections revealed a higher MOI in patients with uncomplicated disease, with the P. falciparum K1 MSP1 (MSP1-K1) and MSP2-3D7 being the most discriminative allelic markers. Higher MOIs also correlated positively with higher antibody levels in several of the ELISAs. In conclusion, certain antibody responses and MOIs were associated with differences between uncomplicated and severe malaria. When different assays were combined, some antibodies, like those against AMA1, seemed particularly discriminative. However, only decreased invasion correlated with initial parasitemia in the patient, signaling the importance of functional assays in understanding development of immunity against malaria and in evaluating vaccine candidates. (Less)
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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apical membrane antigen-1, blood-stage antigens, growth-inhibitory, antibodies, erythrocyte-binding antigens, amyloid-like fibrils, c-terminal fragment, surface protein-2, clinical malaria, in-vitro, vaccine candidate
in
Clinical and Vaccine Immunology
volume
20
issue
8
pages
1170 - 1180
publisher
American Society for Microbiology
external identifiers
  • scopus:84880887960
ISSN
1556-6811
DOI
10.1128/cvi.00156-13
language
English
LU publication?
no
id
96724c95-e6c5-4a56-a1ed-cd96f9632db7 (old id 8726597)
date added to LUP
2016-02-19 13:06:26
date last changed
2019-07-02 01:06:14
@article{96724c95-e6c5-4a56-a1ed-cd96f9632db7,
  abstract     = {Malaria can present itself as an uncomplicated or severe disease. We have here studied the quantity and quality of antibody responses against merozoite antigens, as well as multiplicity of infection (MOI), in children from Uganda. We found higher levels of IgG antibodies toward erythrocyte-binding antigen EBA181, MSP2 of Plasmodium falciparum 3D7 and FC27 (MSP2-3D7/FC27), and apical membrane antigen 1 (AMA1) in patients with uncomplicated malaria by enzyme-linked immunosorbent assay (ELISA) but no differences against EBA140, EBA175, MSP1, and reticulocyte-binding protein homologues Rh2 and Rh4 or for IgM against MSP2-3D7/FC27. Patients with uncomplicated malaria were also shown to have higher antibody affinities for AMA1 by surface plasmon resonance (SPR). Decreased invasion of two clinical P. falciparum isolates in the presence of patient plasma correlated with lower initial parasitemia in the patients, in contrast to comparisons of parasitemia to ELISA values or antibody affinities, which did not show any correlations. Analysis of the heterogeneity of the infections revealed a higher MOI in patients with uncomplicated disease, with the P. falciparum K1 MSP1 (MSP1-K1) and MSP2-3D7 being the most discriminative allelic markers. Higher MOIs also correlated positively with higher antibody levels in several of the ELISAs. In conclusion, certain antibody responses and MOIs were associated with differences between uncomplicated and severe malaria. When different assays were combined, some antibodies, like those against AMA1, seemed particularly discriminative. However, only decreased invasion correlated with initial parasitemia in the patient, signaling the importance of functional assays in understanding development of immunity against malaria and in evaluating vaccine candidates.},
  author       = {Ismail, H. A. and Ribacke, U. and Reiling, L. and Normark, J. and Egwang, T. and Kironde, F. and Beeson, J. G. and Wahlgren, M. and Persson, Kristina},
  issn         = {1556-6811},
  keyword      = {apical membrane antigen-1,blood-stage antigens,growth-inhibitory,antibodies,erythrocyte-binding antigens,amyloid-like fibrils,c-terminal fragment,surface protein-2,clinical malaria,in-vitro,vaccine candidate},
  language     = {eng},
  number       = {8},
  pages        = {1170--1180},
  publisher    = {American Society for Microbiology},
  series       = {Clinical and Vaccine Immunology},
  title        = {Acquired Antibodies to Merozoite Antigens in Children from Uganda with Uncomplicated or Severe Plasmodium falciparum Malaria},
  url          = {http://dx.doi.org/10.1128/cvi.00156-13},
  volume       = {20},
  year         = {2013},
}