Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection

Richard J. Pleass, Solabomi A. Ogun, David H. McGuinness, Jan G. J. van de Winkel, Anthony A. Holder, Jenny M. Woof

    Research output: Contribution to journalArticle

    32 Citations (Scopus)

    Abstract

    Parasite drug resistance and difficulties in developing effective vaccines have precipitated the search for alternative therapies for malaria. The success of passive immunization suggests that immunoglobulin (Ig)-based therapies are effective. To further explore the mechanism(s) by which antibody mediates its protective effect, we generated human chimeric IgG1 and IgA1 and a single-chain diabody specific for the C-terminal 19-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP119), a major target of protective immune responses. These novel human reagents triggered in vitro phagocytosis of merozoites but, unlike their parental mouse IgG2b, failed to protect against parasite challenge in vivo. Therefore, the Fc region appears critical for mediating protection in vivo, at least for this MSP119 epitope. Such antibodies may serve as prototype therapeutic agents, and as useful tools in the development of in vitro neutralization assays with Plasmodium parasites.
    Original languageEnglish
    Pages (from-to)4424-4430
    Number of pages7
    JournalBlood
    Volume102
    Issue number13
    DOIs
    Publication statusPublished - 2003

    Fingerprint

    Antimalarials
    Parasites
    Passive Immunization
    Antibodies
    Merozoite Surface Protein 1
    Plasmodium yoelii
    Immunization
    Merozoites
    Plasmodium
    Complementary Therapies
    Phagocytosis
    Drug Resistance
    Immunoglobulin A
    Malaria
    Immunoglobulins
    Epitopes
    Assays
    Vaccines
    Immunoglobulin G
    Pharmaceutical Preparations

    Cite this

    Pleass, R. J., Ogun, S. A., McGuinness, D. H., van de Winkel, J. G. J., Holder, A. A., & Woof, J. M. (2003). Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection. Blood, 102(13), 4424-4430. https://doi.org/10.1182/blood-2003-02-0583
    Pleass, Richard J. ; Ogun, Solabomi A. ; McGuinness, David H. ; van de Winkel, Jan G. J. ; Holder, Anthony A. ; Woof, Jenny M. / Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection. In: Blood. 2003 ; Vol. 102, No. 13. pp. 4424-4430.
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    abstract = "Parasite drug resistance and difficulties in developing effective vaccines have precipitated the search for alternative therapies for malaria. The success of passive immunization suggests that immunoglobulin (Ig)-based therapies are effective. To further explore the mechanism(s) by which antibody mediates its protective effect, we generated human chimeric IgG1 and IgA1 and a single-chain diabody specific for the C-terminal 19-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP119), a major target of protective immune responses. These novel human reagents triggered in vitro phagocytosis of merozoites but, unlike their parental mouse IgG2b, failed to protect against parasite challenge in vivo. Therefore, the Fc region appears critical for mediating protection in vivo, at least for this MSP119 epitope. Such antibodies may serve as prototype therapeutic agents, and as useful tools in the development of in vitro neutralization assays with Plasmodium parasites.",
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    note = "dc.publisher: American Society of Hematology Senior author responsible for strategy, funding, planning, analysis and writing paper describing generation and characterization of novel malarial specific antibodies that may have potential as reagents for treatment of this globally important disease. This collaborative research was instigated and conducted in my lab and our relative contribution was approximately 90{\%}.",
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    Pleass, RJ, Ogun, SA, McGuinness, DH, van de Winkel, JGJ, Holder, AA & Woof, JM 2003, 'Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection', Blood, vol. 102, no. 13, pp. 4424-4430. https://doi.org/10.1182/blood-2003-02-0583

    Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection. / Pleass, Richard J.; Ogun, Solabomi A.; McGuinness, David H.; van de Winkel, Jan G. J.; Holder, Anthony A.; Woof, Jenny M.

    In: Blood, Vol. 102, No. 13, 2003, p. 4424-4430.

    Research output: Contribution to journalArticle

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    AU - Holder, Anthony A.

    AU - Woof, Jenny M.

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    AB - Parasite drug resistance and difficulties in developing effective vaccines have precipitated the search for alternative therapies for malaria. The success of passive immunization suggests that immunoglobulin (Ig)-based therapies are effective. To further explore the mechanism(s) by which antibody mediates its protective effect, we generated human chimeric IgG1 and IgA1 and a single-chain diabody specific for the C-terminal 19-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP119), a major target of protective immune responses. These novel human reagents triggered in vitro phagocytosis of merozoites but, unlike their parental mouse IgG2b, failed to protect against parasite challenge in vivo. Therefore, the Fc region appears critical for mediating protection in vivo, at least for this MSP119 epitope. Such antibodies may serve as prototype therapeutic agents, and as useful tools in the development of in vitro neutralization assays with Plasmodium parasites.

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