The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria.
BACKGROUND:Antibodies, particularly cytophilic IgG subclasses, with specificity for asexual blood stage antigens of Plasmodium falciparum, are thought to play an important role in acquired immunity to malaria. Evaluating such responses in longitudinal sero-epidemiological field studies, allied to in...
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2009-10-01
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doaj-bdb6dbd9b16b45cdb0f62da0c64d0ae92020-11-25T01:23:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-10-01410e759010.1371/journal.pone.0007590The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria.David CourtinMayke OesterholtHarm HuismansKwadwo KusiJacqueline MiletCyril BadautOumar GayeWill RoeffenEdmond J RemarqueRobert SauerweinAndré GarciaAdrian J F LutyBACKGROUND:Antibodies, particularly cytophilic IgG subclasses, with specificity for asexual blood stage antigens of Plasmodium falciparum, are thought to play an important role in acquired immunity to malaria. Evaluating such responses in longitudinal sero-epidemiological field studies, allied to increasing knowledge of the immunological mechanisms associated with anti-malarial protection, will help in the development of malaria vaccines. METHODS AND FINDINGS:We conducted a 1-year follow-up study of 305 Senegalese children and identified those resistant or susceptible to malaria. In retrospective analyses we then compared post-follow-up IgG responses to six asexual-stage candidate malaria vaccine antigens in groups of individuals with clearly defined clinical and parasitological histories of infection with P. falciparum. In age-adjusted analyses, children resistant to malaria as well as to high-density parasitemia, had significantly higher IgG1 responses to GLURP and IgG3 responses to MSP2 than their susceptible counterparts. Among those resistant to malaria, high anti-MSP1 IgG1 levels were associated with protection against high-density parasitemia. To assess functional attributes, we used an in vitro parasite growth inhibition assay with purified IgG. Samples from individuals with high levels of IgG directed to MSP1, MSP2 and AMA1 gave the strongest parasite growth inhibition, but a marked age-related decline was observed in these effects. CONCLUSION:Our data are consistent with the idea that protection against P. falciparum malaria in children depends on acquisition of a constellation of appropriate, functionally active IgG subclass responses directed to multiple asexual stage antigens. Our results suggest at least two distinct mechanisms via which antibodies may exert protective effects. Although declining with age, the growth inhibitory effects of purified IgG measurable in vitro reflected levels of anti-AMA1, -MSP1 and -MSP2, but not of anti-GLURP IgG. The latter could act on parasite growth via indirect parasiticidal pathways.http://europepmc.org/articles/PMC2763201?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
David Courtin Mayke Oesterholt Harm Huismans Kwadwo Kusi Jacqueline Milet Cyril Badaut Oumar Gaye Will Roeffen Edmond J Remarque Robert Sauerwein André Garcia Adrian J F Luty |
spellingShingle |
David Courtin Mayke Oesterholt Harm Huismans Kwadwo Kusi Jacqueline Milet Cyril Badaut Oumar Gaye Will Roeffen Edmond J Remarque Robert Sauerwein André Garcia Adrian J F Luty The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria. PLoS ONE |
author_facet |
David Courtin Mayke Oesterholt Harm Huismans Kwadwo Kusi Jacqueline Milet Cyril Badaut Oumar Gaye Will Roeffen Edmond J Remarque Robert Sauerwein André Garcia Adrian J F Luty |
author_sort |
David Courtin |
title |
The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria. |
title_short |
The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria. |
title_full |
The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria. |
title_fullStr |
The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria. |
title_full_unstemmed |
The quantity and quality of African children's IgG responses to merozoite surface antigens reflect protection against Plasmodium falciparum malaria. |
title_sort |
quantity and quality of african children's igg responses to merozoite surface antigens reflect protection against plasmodium falciparum malaria. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2009-10-01 |
description |
BACKGROUND:Antibodies, particularly cytophilic IgG subclasses, with specificity for asexual blood stage antigens of Plasmodium falciparum, are thought to play an important role in acquired immunity to malaria. Evaluating such responses in longitudinal sero-epidemiological field studies, allied to increasing knowledge of the immunological mechanisms associated with anti-malarial protection, will help in the development of malaria vaccines. METHODS AND FINDINGS:We conducted a 1-year follow-up study of 305 Senegalese children and identified those resistant or susceptible to malaria. In retrospective analyses we then compared post-follow-up IgG responses to six asexual-stage candidate malaria vaccine antigens in groups of individuals with clearly defined clinical and parasitological histories of infection with P. falciparum. In age-adjusted analyses, children resistant to malaria as well as to high-density parasitemia, had significantly higher IgG1 responses to GLURP and IgG3 responses to MSP2 than their susceptible counterparts. Among those resistant to malaria, high anti-MSP1 IgG1 levels were associated with protection against high-density parasitemia. To assess functional attributes, we used an in vitro parasite growth inhibition assay with purified IgG. Samples from individuals with high levels of IgG directed to MSP1, MSP2 and AMA1 gave the strongest parasite growth inhibition, but a marked age-related decline was observed in these effects. CONCLUSION:Our data are consistent with the idea that protection against P. falciparum malaria in children depends on acquisition of a constellation of appropriate, functionally active IgG subclass responses directed to multiple asexual stage antigens. Our results suggest at least two distinct mechanisms via which antibodies may exert protective effects. Although declining with age, the growth inhibitory effects of purified IgG measurable in vitro reflected levels of anti-AMA1, -MSP1 and -MSP2, but not of anti-GLURP IgG. The latter could act on parasite growth via indirect parasiticidal pathways. |
url |
http://europepmc.org/articles/PMC2763201?pdf=render |
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