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The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1-19 (PfMSP1 19)

By J. Shi, R.S. McIntosh, J. Adame-Gallegos, P.K. Dehal, M. van Egmond, J.G.J. van de Winkel, S.J. Draper, E.K. Forbes, P.H. Corran, A.A. Holder, J.M. Woof and R.J. Pleass

Abstract

Background: Human immunoglobulin G (IgG) plays an important role in mediating protective immune responses\ud to malaria. Although human serum immunoglobulin A (IgA) is the second most abundant class of antibody in the\ud circulation, its contribution, if any, to protective responses against malaria is not clear.\ud Results: To explore the mechanism(s) by which IgA may mediate a protective effect, we generated fully human\ud IgA specific for the C-terminal 19-kDa region of Plasmodium falciparum merozoite surface protein 1 (PfMSP119), a\ud major target of protective immune responses. This novel human IgA bound antigen with an affinity comparable to\ud that seen for an epitope-matched protective human IgG1. Furthermore, the human IgA induced significantly\ud higher NADPH-mediated oxidative bursts and degranulation from human neutrophils than the epitope-matched\ud human IgG1 from which it was derived. Despite showing efficacy in in vitro functional assays, the human IgA failed\ud to protect against parasite challenge in vivo in mice transgenic for the human Fca receptor (FcaRI/CD89). A\ud minority of the animals treated with IgA, irrespective of FcaRI expression, showed elevated serum TNF-a levels and\ud concomitant mouse anti-human antibody (MAHA) responses.\ud Conclusions: The lack of protection afforded by MSP119-specific IgA against parasite challenge in mice transgenic\ud for human FcaRI suggests that this antibody class does not play a major role in control of infection. However, we\ud cannot exclude the possibility that protective capacity may have been compromised in this model due to rapid\ud clearance and inappropriate bio-distribution of IgA, and differences in FcaRI expression profile between humans\ud and transgenic mic

Topics: Algemeen, Geneeskunde
Year: 2011
OAI identifier: oai:dspace.library.uu.nl:1874/237044
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