Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness

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Title Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness
Author Stanisic, Danielle; Richards, Jack S.; McCallum, Fiona J.; Michon, Pascal; King, Christopher L.; Schoepflin, Sonja; Gilson, Paul R.; Murphy, Vincent J.; Anders, Robin F.; Mueller, Ivo; Beeson, James G.
Journal Name Infection and Immunity
Year Published 2009
Place of publication United States
Publisher American Society for Microbiology
Abstract Substantial evidence indicates that antibodies to Plasmodium falciparum merozoite antigens play a role in protection from malaria, although the precise targets and mechanisms mediating immunity remain unclear. Different malaria antigens induce distinct immunoglobulin G (IgG) subclass responses, but the importance of different responses in protective immunity from malaria is not known and the factors determining subclass responses in vivo are poorly understood. We examined IgG and IgG subclass responses to the merozoite antigens MSP1-19 (the 19-kDa C-terminal region of merozoite surface protein 1), MSP2 (merozoite surface protein 2), and AMA-1 (apical membrane antigen 1), including different polymorphic variants of these antigens, in a longitudinal cohort of children in Papua New Guinea. IgG1 and IgG3 were the predominant subclasses of antibodies to each antigen, and all antibody responses increased in association with age and exposure without evidence of increasing polarization toward one subclass. The profiles of IgG subclasses differed somewhat for different alleles of MSP2 but not for different variants of AMA-1. Individuals did not appear to have a propensity to make a specific subclass response irrespective of the antigen. Instead, data suggest that subclass responses to each antigen are generated independently among individuals and that antigen properties, rather than host factors, are the major determinants of IgG subclass responses. High levels of AMA-1-specific IgG3 and MSP1-19-specific IgG1 were strongly predictive of a reduced risk of symptomatic malaria and high-density P. falciparum infections. However, no antibody response was significantly associated with protection from parasitization per se. Our findings have major implications for understanding human immunity and for malaria vaccine development and evaluation.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1128/IAI.01129-08
Volume 77
Issue Number 3
Page from 1165
Page to 1174
ISSN 0019-9567
Date Accessioned 2011-03-22
Date Available 2011-04-14T07:00:24Z
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Humoural Immunology and Immunochemistry
URI http://hdl.handle.net/10072/38165
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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