The generation and evaluation of recombinant human IgA specific for <it>Plasmodium falciparum </it>merozoite surface protein 1-19 (<it>Pf</it>MSP1<sub>19</sub>)
<p>Abstract</p> <p>Background</p> <p>Human immunoglobulin G (IgG) plays an important role in mediating protective immune responses to malaria. Although human serum immunoglobulin A (IgA) is the second most abundant class of antibody in the circulation, its contribution,...
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| Format: | Article |
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BMC
2011-07-01
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| Series: | BMC Biotechnology |
| Online Access: | http://www.biomedcentral.com/1472-6750/11/77 |
| _version_ | 1818778668784156672 |
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| author | Corran Patrick H Forbes Emily K Draper Simon J van de Winkel Jan van Egmond Marjolein Dehal Prabhjyot K Adame-Gallegos Jaime McIntosh Richard S Shi Jianguo Holder Anthony A Woof Jenny M Pleass Richard J |
| author_facet | Corran Patrick H Forbes Emily K Draper Simon J van de Winkel Jan van Egmond Marjolein Dehal Prabhjyot K Adame-Gallegos Jaime McIntosh Richard S Shi Jianguo Holder Anthony A Woof Jenny M Pleass Richard J |
| author_sort | Corran Patrick H |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Human immunoglobulin G (IgG) plays an important role in mediating protective immune responses to malaria. Although human serum immunoglobulin A (IgA) is the second most abundant class of antibody in the circulation, its contribution, if any, to protective responses against malaria is not clear.</p> <p>Results</p> <p>To explore the mechanism(s) by which IgA may mediate a protective effect, we generated fully human IgA specific for the C-terminal 19-kDa region of <it>Plasmodium falciparum </it>merozoite surface protein 1 (<it>Pf</it>MSP1<sub>19</sub>), a major target of protective immune responses. This novel human IgA bound antigen with an affinity comparable to that seen for an epitope-matched protective human IgG1. Furthermore, the human IgA induced significantly higher NADPH-mediated oxidative bursts and degranulation from human neutrophils than the epitope-matched human IgG1 from which it was derived. Despite showing efficacy in <it>in vitro </it>functional assays, the human IgA failed to protect against parasite challenge <it>in vivo </it>in mice transgenic for the human Fcα receptor (FcαRI/CD89). A minority of the animals treated with IgA, irrespective of FcαRI expression, showed elevated serum TNF-α levels and concomitant mouse anti-human antibody (MAHA) responses.</p> <p>Conclusions</p> <p>The lack of protection afforded by MSP1<sub>19</sub>-specific IgA against parasite challenge in mice transgenic for human FcαRI suggests that this antibody class does not play a major role in control of infection. However, we cannot exclude the possibility that protective capacity may have been compromised in this model due to rapid clearance and inappropriate bio-distribution of IgA, and differences in FcαRI expression profile between humans and transgenic mice.</p> |
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| institution | Directory Open Access Journal |
| issn | 1472-6750 |
| language | English |
| last_indexed | 2024-12-18T11:48:23Z |
| publishDate | 2011-07-01 |
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| series | BMC Biotechnology |
| spelling | doaj.art-a417049603334c60ad7f1ba802ac4dc02022-12-21T21:09:13ZengBMCBMC Biotechnology1472-67502011-07-011117710.1186/1472-6750-11-77The generation and evaluation of recombinant human IgA specific for <it>Plasmodium falciparum </it>merozoite surface protein 1-19 (<it>Pf</it>MSP1<sub>19</sub>)Corran Patrick HForbes Emily KDraper Simon Jvan de Winkel Janvan Egmond MarjoleinDehal Prabhjyot KAdame-Gallegos JaimeMcIntosh Richard SShi JianguoHolder Anthony AWoof Jenny MPleass Richard J<p>Abstract</p> <p>Background</p> <p>Human immunoglobulin G (IgG) plays an important role in mediating protective immune responses to malaria. Although human serum immunoglobulin A (IgA) is the second most abundant class of antibody in the circulation, its contribution, if any, to protective responses against malaria is not clear.</p> <p>Results</p> <p>To explore the mechanism(s) by which IgA may mediate a protective effect, we generated fully human IgA specific for the C-terminal 19-kDa region of <it>Plasmodium falciparum </it>merozoite surface protein 1 (<it>Pf</it>MSP1<sub>19</sub>), a major target of protective immune responses. This novel human IgA bound antigen with an affinity comparable to that seen for an epitope-matched protective human IgG1. Furthermore, the human IgA induced significantly higher NADPH-mediated oxidative bursts and degranulation from human neutrophils than the epitope-matched human IgG1 from which it was derived. Despite showing efficacy in <it>in vitro </it>functional assays, the human IgA failed to protect against parasite challenge <it>in vivo </it>in mice transgenic for the human Fcα receptor (FcαRI/CD89). A minority of the animals treated with IgA, irrespective of FcαRI expression, showed elevated serum TNF-α levels and concomitant mouse anti-human antibody (MAHA) responses.</p> <p>Conclusions</p> <p>The lack of protection afforded by MSP1<sub>19</sub>-specific IgA against parasite challenge in mice transgenic for human FcαRI suggests that this antibody class does not play a major role in control of infection. However, we cannot exclude the possibility that protective capacity may have been compromised in this model due to rapid clearance and inappropriate bio-distribution of IgA, and differences in FcαRI expression profile between humans and transgenic mice.</p>http://www.biomedcentral.com/1472-6750/11/77 |
| spellingShingle | Corran Patrick H Forbes Emily K Draper Simon J van de Winkel Jan van Egmond Marjolein Dehal Prabhjyot K Adame-Gallegos Jaime McIntosh Richard S Shi Jianguo Holder Anthony A Woof Jenny M Pleass Richard J The generation and evaluation of recombinant human IgA specific for <it>Plasmodium falciparum </it>merozoite surface protein 1-19 (<it>Pf</it>MSP1<sub>19</sub>) BMC Biotechnology |
| title | The generation and evaluation of recombinant human IgA specific for <it>Plasmodium falciparum </it>merozoite surface protein 1-19 (<it>Pf</it>MSP1<sub>19</sub>) |
| title_full | The generation and evaluation of recombinant human IgA specific for <it>Plasmodium falciparum </it>merozoite surface protein 1-19 (<it>Pf</it>MSP1<sub>19</sub>) |
| title_fullStr | The generation and evaluation of recombinant human IgA specific for <it>Plasmodium falciparum </it>merozoite surface protein 1-19 (<it>Pf</it>MSP1<sub>19</sub>) |
| title_full_unstemmed | The generation and evaluation of recombinant human IgA specific for <it>Plasmodium falciparum </it>merozoite surface protein 1-19 (<it>Pf</it>MSP1<sub>19</sub>) |
| title_short | The generation and evaluation of recombinant human IgA specific for <it>Plasmodium falciparum </it>merozoite surface protein 1-19 (<it>Pf</it>MSP1<sub>19</sub>) |
| title_sort | generation and evaluation of recombinant human iga specific for it plasmodium falciparum it merozoite surface protein 1 19 it pf it msp1 sub 19 sub |
| url | http://www.biomedcentral.com/1472-6750/11/77 |
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