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.