TY - JOUR
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 -
