Human recombinant antibodies against Plasmodium falciparum merozoite surface protein 3 cloned from peripheral blood leukocytes of individuals with immunity to malaria demonstrate antiparasitic properties

TY - JOUR

T1 - Human recombinant antibodies against Plasmodium falciparum merozoite surface protein 3 cloned from peripheral blood leukocytes of individuals with immunity to malaria demonstrate antiparasitic properties

AU - Lundquist, Rasmus

AU - Nielsen, Leif Kofoed

AU - Jafarshad, Ali

AU - Soesoe, Daw

AU - Christensen, Lars Harder

AU - Druilhe, Pierre

AU - Dziegiel, Morten Hanefeld

PY - 2006/6

Y1 - 2006/6

N2 - Immunoglobulins from individuals with immunity to malaria have a strong antiparasitic effect when transferred to Plasmodium falciparum malaria infected patients. One prominent target of antiparasitic antibodies is the merozoite surface antigen 3 (MSP-3). We have investigated the antibody response against MSP-3 residues 194 to 257 (MSP-3(194-257)) on the molecular level. mRNA from peripheral blood leukocytes from clinically immune individuals was used as a source of Fab (fragment antibody) genes. A Fab-phage display library was made, and three distinct antibodies designated RAM1, RAM2, and RAM3 were isolated by panning. Immunoglobulin G1 (IgG1) and IgG3 full-length antibodies have been produced in CHO cells. Reactivity with the native parasite protein was demonstrated by immunofluorescence microscopy, flow cytometry, and immunoblotting. Furthermore, the antiparasitic effect of RAM1 has been tested in vitro in an antibody-dependent cellular inhibition (ADCI) assay. Both the IgG1 and the IgG3 versions of the antibody show an inhibitory effect on parasite growth.

AB - Immunoglobulins from individuals with immunity to malaria have a strong antiparasitic effect when transferred to Plasmodium falciparum malaria infected patients. One prominent target of antiparasitic antibodies is the merozoite surface antigen 3 (MSP-3). We have investigated the antibody response against MSP-3 residues 194 to 257 (MSP-3(194-257)) on the molecular level. mRNA from peripheral blood leukocytes from clinically immune individuals was used as a source of Fab (fragment antibody) genes. A Fab-phage display library was made, and three distinct antibodies designated RAM1, RAM2, and RAM3 were isolated by panning. Immunoglobulin G1 (IgG1) and IgG3 full-length antibodies have been produced in CHO cells. Reactivity with the native parasite protein was demonstrated by immunofluorescence microscopy, flow cytometry, and immunoblotting. Furthermore, the antiparasitic effect of RAM1 has been tested in vitro in an antibody-dependent cellular inhibition (ADCI) assay. Both the IgG1 and the IgG3 versions of the antibody show an inhibitory effect on parasite growth.

KW - Adult

KW - Amino Acid Sequence

KW - Antibodies, Protozoan

KW - Antigens, Protozoan

KW - Blotting, Western

KW - Enzyme-Linked Immunosorbent Assay

KW - Epitope Mapping

KW - Flow Cytometry

KW - Humans

KW - Immunoglobulin Fab Fragments

KW - Immunoglobulin G

KW - Leukocytes

KW - Malaria

KW - Microscopy, Fluorescence

KW - Molecular Sequence Data

KW - Peptide Library

KW - Protozoan Proteins

KW - Recombinant Proteins

U2 - 10.1128/IAI.00928-05

DO - 10.1128/IAI.00928-05

M3 - Journal article

C2 - 16714549

SN - 0019-9567

VL - 74

SP - 3222

EP - 3231

JO - Infection and Immunity

JF - Infection and Immunity

IS - 6

ER -