Conserved Regions From Plasmodium falciparum MSP11 Specifically Interact With Host Cells and Have a Potential Role During Merozoite Invasion of Red Blood Cells Ana Zuleima Obando-Martinez, 1,2 Hernando Curtidor, 1,2 Magnolia Vanegas, 1,2 Gabriela Are ´valo-Pinzo ´n, 1,2 Manuel Alfonso Patarroyo, 1,2 and Manuel Elkin Patarroyo 1,3 * 1 Fundacio ´n Instituto de Inmunologı ´a de Colombia, Carrera 50 No. 26-20, Bogota ´, Colombia 2 Universidad del Rosario, Calle 14 No. 6-25, Bogota ´, Colombia 3 Universidad Nacional de Colombia, Carrera 45 No 26-85, Bogota ´, Colombia ABSTRACT Despite significant global efforts, a completely effective vaccine against Plasmodium falciparum, the species responsible for the most serious form of malaria, has not been yet obtained. One of the most promising approaches consists in combining chemically synthesized minimal subunits of parasite proteins involved in host cell invasion, which has led to the identification of peptides with high binding activity (named HABPs) to hepatocyte and red blood cell (RBC) surface receptors in a large number of sporozoite and merozoite proteins, respectively. Among these proteins is the merozoite surface protein 11 (MSP11), which shares important structural and immunological features with the antimalarial vaccine candidates MSP1, MSP3, and MSP6. In this study, 20-mer-long synthetic peptides spanning the complete sequence of MSP11 were assessed for their ability to bind specifically to RBCs. Two HABPs with high ability to inhibit invasion of RBCs in vitro were identified (namely HABPs 33595 and 33606). HABP-RBC bindings were characterized by means of saturation assays and Hill analysis, finding cooperative interactions of high affinity for both HABPs (n H of 1.5 and 1.2, K d of 800 and 600 nM for HABPs 33595 and 33606, respectively). The nature of the possible RBC receptors for MSP11 HABPs was studied in binding assays to enzyme-treated RBCs and cross-linking assays, finding that both HABPs use mainly a sialic acid-dependent receptor. An analysis of the immunological, structural and polymorphic characteristics of MSP11 HABPs supports including these peptides in further studies with the aim of designing a fully effective protection- inducing vaccine against malaria. J. Cell. Biochem. 110: 882–892, 2010. ß 2010 Wiley-Liss, Inc. KEY WORDS: MEROZOITE SURFACE PROTEIN 11; H103; Plasmodium falciparum; MEROZOITE INVASION OF RED BLOOD CELLS; MOLECULAR INTERACTIONS HOST–PATHOGEN; ANTIMALARIAL VACCINE; SYNTHETIC PEPTIDES T he Plasmodium falciparum parasite causes the most serious form of malaria, which is considered as one of the most important infectious diseases worldwide since it annually affects around 250 million people causing the death of 1 million of them [WHO, 2008]. Control of malaria has been significantly hampered by the emergence of drug-resistant parasites and the spread of insecticide-resistant mosquito vectors [Mita et al., 2008; Munhenga et al., 2008]. A potent vaccine has been therefore considered as the most cost-effective measure to help eradicate this dreadful disease. In particular, our approach to develop a fully effective antimalarial vaccine has consisted in including multiple conserved epitopes of functionally relevant proteins from the different parasite life-cycle stages, especially those involved in invasion of hepatocytes and red blood cells (RBCs) [Patarroyo and Patarroyo, 2008]. With such purpose in mind, we have worked in the identification of amino acid sequences from proteins expressed during the asexual life cycle that have a potential role in parasite invasion of RBCs and therefore could be included as components of a multi-epitopic, multistage, minimal subunit-based, chemically synthesized antimalarial vaccine [Patarroyo and Patarroyo, 2008]. The malaria parasite P. falciparum uses different pathways to invade RBCs that are mediated by receptor–ligand molecular interactions between merozoite proteins and RBC surface receptors. A large number of these merozoite invasion proteins have been Journal of Cellular Biochemistry ARTICLE Journal of Cellular Biochemistry 110:882–892 (2010) 882 Additional Supporting Information may be found in the online version of this article. *Correspondence to: Prof. Manuel Elkin Patarroyo, Carrera 50 No. 26-20, Bogota ´, Colombia. E-mail: mepatarr@mail.com Received 26 November 2009; Accepted 1 March 2010  DOI 10.1002/jcb.22600  ß 2010 Wiley-Liss, Inc. Published online 14 April 2010 in Wiley InterScience (www.interscience.wiley.com).