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

Jianguo Shi, Richard S. McIntosh, Jaime Adame-Gallegos, Prabhjyot K. Dehal, Marjolein van Egmond, Jan van de Winkel, Simon J. Draper, Emily K. Forbes, Patrick H. Corran, Anthony A. Holder, Jennifer Woof, Richard J. Pleass

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    Abstract

    Background: 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.

    Results: 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 Plasmodium falciparum merozoite surface protein 1 (PfMSP1(19)), 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 in vitro functional assays, the human IgA failed to protect against parasite challenge in vivo in mice transgenic for the human Fc alpha receptor (Fc alpha RI/CD89). A minority of the animals treated with IgA, irrespective of Fc alpha RI expression, showed elevated serum TNF-alpha levels and concomitant mouse anti-human antibody (MAHA) responses.

    Conclusions: The lack of protection afforded by MSP1(19)-specific IgA against parasite challenge in mice transgenic for human FcaRI 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 FcaRI expression profile between humans and transgenic mice.

    Original languageEnglish
    Article number77
    Pages (from-to)-
    Number of pages8
    JournalBMC Biotechnology
    Volume11
    DOIs
    Publication statusPublished - 22 Jul 2011

    Keywords

    • FC-ALPHA-RI
    • IMMUNOGLOBULIN-A
    • RECEPTOR
    • MALARIA
    • ANTIBODY
    • PROTECTION
    • CD89
    • INFLAMMATION
    • NEUTROPHILS
    • EXPRESSION

    Cite this

    Shi, J., McIntosh, R. S., Adame-Gallegos, J., Dehal, P. K., van Egmond, M., van de Winkel, J., ... Pleass, R. J. (2011). The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1-19 (PfMSP1(19)). BMC Biotechnology, 11, -. [77]. https://doi.org/10.1186/1472-6750-11-77
    Shi, Jianguo ; McIntosh, Richard S. ; Adame-Gallegos, Jaime ; Dehal, Prabhjyot K. ; van Egmond, Marjolein ; van de Winkel, Jan ; Draper, Simon J. ; Forbes, Emily K. ; Corran, Patrick H. ; Holder, Anthony A. ; Woof, Jennifer ; Pleass, Richard J. / The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1-19 (PfMSP1(19)). In: BMC Biotechnology. 2011 ; Vol. 11. pp. -.
    @article{b7161119105c494a9c4f5ec0392d8497,
    title = "The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1-19 (PfMSP1(19))",
    abstract = "Background: 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.Results: 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 Plasmodium falciparum merozoite surface protein 1 (PfMSP1(19)), 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 in vitro functional assays, the human IgA failed to protect against parasite challenge in vivo in mice transgenic for the human Fc alpha receptor (Fc alpha RI/CD89). A minority of the animals treated with IgA, irrespective of Fc alpha RI expression, showed elevated serum TNF-alpha levels and concomitant mouse anti-human antibody (MAHA) responses.Conclusions: The lack of protection afforded by MSP1(19)-specific IgA against parasite challenge in mice transgenic for human FcaRI 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 FcaRI expression profile between humans and transgenic mice.",
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    author = "Jianguo Shi and McIntosh, {Richard S.} and Jaime Adame-Gallegos and Dehal, {Prabhjyot K.} and {van Egmond}, Marjolein and {van de Winkel}, Jan and Draper, {Simon J.} and Forbes, {Emily K.} and Corran, {Patrick H.} and Holder, {Anthony A.} and Jennifer Woof and Pleass, {Richard J.}",
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    Shi, J, McIntosh, RS, Adame-Gallegos, J, Dehal, PK, van Egmond, M, van de Winkel, J, Draper, SJ, Forbes, EK, Corran, PH, Holder, AA, Woof, J & Pleass, RJ 2011, 'The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1-19 (PfMSP1(19))', BMC Biotechnology, vol. 11, 77, pp. -. https://doi.org/10.1186/1472-6750-11-77

    The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1-19 (PfMSP1(19)). / Shi, Jianguo; McIntosh, Richard S.; Adame-Gallegos, Jaime; Dehal, Prabhjyot K.; van Egmond, Marjolein; van de Winkel, Jan; Draper, Simon J.; Forbes, Emily K.; Corran, Patrick H.; Holder, Anthony A.; Woof, Jennifer; Pleass, Richard J.

    In: BMC Biotechnology, Vol. 11, 77, 22.07.2011, p. -.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1-19 (PfMSP1(19))

    AU - Shi, Jianguo

    AU - McIntosh, Richard S.

    AU - Adame-Gallegos, Jaime

    AU - Dehal, Prabhjyot K.

    AU - van Egmond, Marjolein

    AU - van de Winkel, Jan

    AU - Draper, Simon J.

    AU - Forbes, Emily K.

    AU - Corran, Patrick H.

    AU - Holder, Anthony A.

    AU - Woof, Jennifer

    AU - Pleass, Richard J.

    PY - 2011/7/22

    Y1 - 2011/7/22

    N2 - Background: 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.Results: 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 Plasmodium falciparum merozoite surface protein 1 (PfMSP1(19)), 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 in vitro functional assays, the human IgA failed to protect against parasite challenge in vivo in mice transgenic for the human Fc alpha receptor (Fc alpha RI/CD89). A minority of the animals treated with IgA, irrespective of Fc alpha RI expression, showed elevated serum TNF-alpha levels and concomitant mouse anti-human antibody (MAHA) responses.Conclusions: The lack of protection afforded by MSP1(19)-specific IgA against parasite challenge in mice transgenic for human FcaRI 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 FcaRI expression profile between humans and transgenic mice.

    AB - Background: 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.Results: 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 Plasmodium falciparum merozoite surface protein 1 (PfMSP1(19)), 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 in vitro functional assays, the human IgA failed to protect against parasite challenge in vivo in mice transgenic for the human Fc alpha receptor (Fc alpha RI/CD89). A minority of the animals treated with IgA, irrespective of Fc alpha RI expression, showed elevated serum TNF-alpha levels and concomitant mouse anti-human antibody (MAHA) responses.Conclusions: The lack of protection afforded by MSP1(19)-specific IgA against parasite challenge in mice transgenic for human FcaRI 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 FcaRI expression profile between humans and transgenic mice.

    KW - FC-ALPHA-RI

    KW - IMMUNOGLOBULIN-A

    KW - RECEPTOR

    KW - MALARIA

    KW - ANTIBODY

    KW - PROTECTION

    KW - CD89

    KW - INFLAMMATION

    KW - NEUTROPHILS

    KW - EXPRESSION

    U2 - 10.1186/1472-6750-11-77

    DO - 10.1186/1472-6750-11-77

    M3 - Article

    VL - 11

    SP - -

    JO - BMC Biotechnology

    JF - BMC Biotechnology

    SN - 1472-6750

    M1 - 77

    ER -