Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection.
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.
Pleass
Richard J
RJ
School of Biology, University Park, Nottingham, NG7 2RD, United Kingdom. richard.pleass@nottingham.ac.uk
Ogun
Solabomi A
SA
McGuinness
David H
DH
van de Winkel
Jan G J
JG
Holder
Anthony A
AA
Woof
Jenny M
JM
D000818:Animals; D000913:Antibodies, Protozoan / Q000737:chemistry / Q000276:immunology*; D004789:Enzyme Activation; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007070:Immunoglobulin A / Q000737:chemistry / Q000276:immunology*; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology*; D008288:Malaria / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019255:NADPH Oxidases / Q000378:metabolism; D009500:Neutralization Tests; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology; D018512:Parasitemia / Q000517:prevention & control; D010587:Phagocytosis; D010967:Plasmodium yoelii / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000913:Antibodies, Protozoan; D000939:Epitopes; D007070:Immunoglobulin A; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D020066:Merozoite Surface Protein 1; D011993:Recombinant Fusion Proteins; D019255:NADPH Oxidases