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Infection and Immunity, February 2006, p. 1313-1322, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1313-1322.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria Parasite Plasmodium falciparum

Ute Woehlbier,1 Christian Epp,1 Christian W. Kauth,1 Rolf Lutz,1 Carole A. Long,2 Boubacar Coulibaly,3 Bocar Kouyaté,3 Myriam Arevalo-Herrera,4 Sócrates Herrera,4 and Hermann Bujard1*

Zentrum fuer Molekulare Biologie (ZMBH), Universitaet Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany,1 Malaria Vaccine Development Branch, NIAID, National Institutes of Health, Rockville, Maryland 20852,2 Centre de Recherche en Santé de Nouna (CRSN), Nouna, Burkina Faso,3 Centro Internacional de Vacunas, Carrera 35 No. 4A-53, Cali, Colombia4

Received 1 July 2005/ Returned for modification 31 August 2005/ Accepted 27 October 2005

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.

* Corresponding author. Mailing address: Zentrum fuer Molekulare Biologie (ZMBH), Universitaet Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany. Phone: 49-6221 54 8214. Fax: 49-6221 54 5892. E-mail: h.bujard{at}zmbh.uni-heidelberg.de.

Editor: J. L. Flynn

Infection and Immunity, February 2006, p. 1313-1322, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1313-1322.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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