title: Epitope specificity and capacity to inhibit parasite growth in vitro of human antibodies to repeat sequences of the Plasmodium falciparum antigen Ag332.
abstract: It has earlier been shown that the Plasmodium falciparum-reactive human monoclonal antibody 33G2 inhibits parasite growth in vitro as well as cytoadherence of infected red blood cells to melanoma cells in vitro. MoAb 33G2 recognizes an epitope of the P. falciparum antigen Ag332 and cross-reactive determinants in Pf155/RESA and Pf11.1 located in repetitive regions containing sequences of regularly spaced pairs of glutamic acid. To study whether antibodies of this specificity frequently occur in human immune sera and if they could be of importance for protective immunity, antibodies were affinity purified on MoAb 33G2 reactive Ag332 peptides. The epitope specificity of the affinity purified antibodies, determined by the Pepscan method, resembled that of MoAb 33G2, but showed differences in fine specificity. The antibodies cross-reacted to some extent with Pf11.1 and Pf155/RESA repeat peptides as detected by peptide ELISA and Pepscan. In indirect immunofluorescence all purified antibodies displayed a dotted pattern of staining of late stage infected red blood cells of two lines of the P. falciparum strain FCR3, including a Pf155/RESA deficient line. The in vitro growth of these two lines was efficiently inhibited by the affinity purified antibodies, indicating that their inhibitory effect was mainly due to reactivity with antigens other than Pf155/RESA. This, and the fact that Pf11.1 has been shown not to be expressed by the asexual stages suggests that Ag332 may be an important target for potentially protective antibodies in vivo and that Ag332 based immunogens are of interest for development of malaria subunit vaccines.
authors.affiliation: Department of Immunology, Stockholm University, Sweden.
authors.forename: N
authors.initials: N
authors.lastname: Ahlborg
authors.forename: B W
authors.initials: BW
authors.lastname: Flyg
authors.forename: J
authors.initials: J
authors.lastname: Iqbal
authors.forename: P
authors.initials: P
authors.lastname: Perlmann
authors.forename: K
authors.initials: K
authors.lastname: Berzins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification; D000913:Antibodies, Protozoan / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology; D002460:Cell Line; D003429:Cross Reactions; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D007074:Immunoglobulin G; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum; C073415:antigen Pf332, Plasmodium