title: Analysis of antibodies directed against merozoite surface protein 1 of the human malaria parasite Plasmodium falciparum.
abstract: The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria.
authors.affiliation: Zentrum fuer Molekulare Biologie (ZMBH), Universitaet Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Woehlbier
authors.forename: Christian
authors.initials: C
authors.lastname: Epp
authors.forename: Christian W
authors.initials: CW
authors.lastname: Kauth
authors.forename: Rolf
authors.initials: R
authors.lastname: Lutz
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Boubacar
authors.initials: B
authors.lastname: Coulibaly
authors.forename: Bocar
authors.initials: B
authors.lastname: Kouyaté
authors.forename: Myriam
authors.initials: M
authors.lastname: Arevalo-Herrera
authors.forename: Sócrates
authors.initials: S
authors.lastname: Herrera
authors.forename: Hermann
authors.initials: H
authors.lastname: Bujard
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology*; D000918:Antibody Specificity; D004912:Erythrocytes / Q000469:parasitology; D005434:Flow Cytometry; D006801:Humans; D007114:Immunization; D017780:Malaria Vaccines; D016778:Malaria, Falciparum / Q000517:prevention & control; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000276:immunology*; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology*; D011817:Rabbits
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1