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Human Recombinant Antibodies against Plasmodium falciparum Merozoite Surface Protein 3 Cloned from Peripheral Blood Leukocytes of Individuals with Immunity to Malaria Demonstrate Antiparasitic Properties

Author:
Lundquist, Rasmus, Nielsen, Leif Kofoed, Jafarshad, Ali, SoeSoe, Daw, Christensen, Lars Harder, Druilhe, Pierre, Dziegiel, Morten Hanefeld
Source:
Infection and immunity 2006 v.74 no.6 pp. 3222-3231
ISSN:
0019-9567
Subject:
Plasmodium falciparum, antigens, antiparasitic agents, flow cytometry, genes, humans, immunity, immunoblotting, immunoglobulins, leukocytes, malaria, merozoites, messenger RNA, parasites, patients, recombinant antibodies, surface proteins
Abstract:
Immunoglobulinsfrom individuals with immunity to malaria have a strong antiparasiticeffect when transferred to Plasmodium falciparum malariainfected patients. One prominent target of antiparasitic antibodies isthe merozoite surface antigen 3 (MSP-3). We have investigated theantibody response against MSP-3 residues 194 to 257(MSP-3₁₉₄₋₂₅₇) on the molecular level. mRNA fromperipheral blood leukocytes from clinically immune individuals was usedas a source of Fab (fragment antibody) genes. A Fab-phage displaylibrary was made, and three distinct antibodies designated RAM1, RAM2,and RAM3 were isolated by panning. Immunoglobulin G1 (IgG1) and IgG3full-length antibodies have been produced in CHO cells. Reactivity withthe native parasite protein was demonstrated by immunofluorescencemicroscopy, flow cytometry, and immunoblotting. Furthermore, theantiparasitic effect of RAM1 has been tested in vitro in anantibody-dependent cellular inhibition (ADCI) assay. Both the IgG1 andthe IgG3 versions of the antibody show an inhibitory effect on parasitegrowth.
Agid:
267914