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High Affinity Antibodies to Plasmodium falciparum Merozoite Antigens Are Associated with Protection from Malaria

Reddy, Sreenivasulu B.; Anders, Robin F.; Beeson, James G.; Farnert, Anna; Kironde, Fred; Berenzon, Sharon Kuhlman; Wahlgren, Mats; Linse, Sara LU and Persson, Kristina LU (2012) In PLoS ONE 7(2).
Abstract
Background: Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown. Methodology/Principal Findings: In this study, surface plasmon resonance technology was used to evaluate the affinity (measured as kd) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The... (More)
Background: Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown. Methodology/Principal Findings: In this study, surface plasmon resonance technology was used to evaluate the affinity (measured as kd) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The finding of MSP2-3D7 type parasites in the blood was associated with a tendency for higher affinity antibodies to both forms of MSP2 and AMA1, but this was significant only when analyzing antibodies against MSP2-FC27, and individuals infected with both allelic forms of MSP2 at the same time showed the highest affinities. Individuals with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged time to clinical malaria during 40 weeks of follow-up, and among individuals who were parasite positive at baseline higher antibody affinities to all antigens were seen in the individuals that did not experience febrile malaria during follow up. Conclusions/Significance: This study contributes important information for understanding how immunity against malaria arises. The findings suggest that antibody affinity plays an important role in protection against disease, and differs between antigens. In light of this information, antibody affinity measurements would be a key assessment in future evaluation of malaria vaccine formulations. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
apical membrane antigen-1, surface protein-2 msp2, amyloid-like fibrils, thiocyanate elution, monoclonal-antibody, immune-response, reduced risk, vaccine, forms, diversity
in
PLoS ONE
volume
7
issue
2
publisher
Public Library of Science
external identifiers
  • scopus:84857415367
  • wos:000302873700159
ISSN
1932-6203
DOI
10.1371/journal.pone.0032242
language
English
LU publication?
yes
id
d75fc1b4-b215-4522-9242-3c4f7b079349 (old id 8726657)
date added to LUP
2016-02-19 13:10:04
date last changed
2017-05-29 09:07:58
@article{d75fc1b4-b215-4522-9242-3c4f7b079349,
  abstract     = {Background: Malaria kills almost 1 million people every year, but the mechanisms behind protective immunity against the disease are still largely unknown. Methodology/Principal Findings: In this study, surface plasmon resonance technology was used to evaluate the affinity (measured as kd) of naturally acquired antibodies to the Plasmodium falciparum antigens MSP2 and AMA1. Antibodies in serum samples from residents in endemic areas bound with higher affinities to AMA1 than to MSP2, and with higher affinities to the 3D7 allele of MSP2-3D7 than to the FC27 allele. The affinities against AMA1 and MSP2-3D7 increased with age, and were usually within similar range as the affinities for the monoclonal antibodies also examined in this study. The finding of MSP2-3D7 type parasites in the blood was associated with a tendency for higher affinity antibodies to both forms of MSP2 and AMA1, but this was significant only when analyzing antibodies against MSP2-FC27, and individuals infected with both allelic forms of MSP2 at the same time showed the highest affinities. Individuals with the highest antibody affinities for MSP2-3D7 at baseline had a prolonged time to clinical malaria during 40 weeks of follow-up, and among individuals who were parasite positive at baseline higher antibody affinities to all antigens were seen in the individuals that did not experience febrile malaria during follow up. Conclusions/Significance: This study contributes important information for understanding how immunity against malaria arises. The findings suggest that antibody affinity plays an important role in protection against disease, and differs between antigens. In light of this information, antibody affinity measurements would be a key assessment in future evaluation of malaria vaccine formulations.},
  articleno    = {e32242},
  author       = {Reddy, Sreenivasulu B. and Anders, Robin F. and Beeson, James G. and Farnert, Anna and Kironde, Fred and Berenzon, Sharon Kuhlman and Wahlgren, Mats and Linse, Sara and Persson, Kristina},
  issn         = {1932-6203},
  keyword      = {apical membrane antigen-1,surface protein-2 msp2,amyloid-like fibrils,thiocyanate elution,monoclonal-antibody,immune-response,reduced risk,vaccine,forms,diversity},
  language     = {eng},
  number       = {2},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {High Affinity Antibodies to Plasmodium falciparum Merozoite Antigens Are Associated with Protection from Malaria},
  url          = {http://dx.doi.org/10.1371/journal.pone.0032242},
  volume       = {7},
  year         = {2012},
}