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

doi:10.1182/blood-2003-02-0583

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 journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	4424-4430
Number of pages	7
Journal	Blood
Volume	102
Issue number	13
DOIs	https://doi.org/10.1182/blood-2003-02-0583
Publication status	Published - 2003

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10.1182/blood-2003-02-0583

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title = "Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection",

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.",

author = "Pleass, {Richard J.} and Ogun, {Solabomi A.} and McGuinness, {David H.} and {van de Winkel}, {Jan G. J.} and Holder, {Anthony A.} and Woof, {Jenny M.}",

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%. ",

year = "2003",

doi = "10.1182/blood-2003-02-0583",

language = "English",

volume = "102",

pages = "4424--4430",

journal = "Blood",

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publisher = "American Society of Hematology",

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T1 - Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection

AU - Pleass, Richard J.

AU - Ogun, Solabomi A.

AU - McGuinness, David H.

AU - van de Winkel, Jan G. J.

AU - Holder, Anthony A.

AU - Woof, Jenny M.

N1 - 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%.

PY - 2003

Y1 - 2003

N2 - 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.

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.

U2 - 10.1182/blood-2003-02-0583

DO - 10.1182/blood-2003-02-0583

M3 - Article

SN - 0006-4971

VL - 102

SP - 4424

EP - 4430

JO - Blood

JF - Blood

IS - 13

ER -

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

Abstract

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