Redefining an epitope of a malaria vaccine candidate, with antibodies against the N-terminal MSA-2 antigen of Plasmodium harboring non-natural peptide bonds.

The aim of obtaining novel vaccine candidates against malaria and other transmissible diseases can be partly based on selecting non-polymorphic peptides from relevant antigens of pathogens, which have to be then precisely modified for inducing a protective immunity against the disease. Bearing in mind the high degree of the MSA-2(21-40) peptide primary structure's genetic conservation among malaria species, and its crucial role in the high RBC binding ability of Plasmodium falciparum (the main agent causing malaria), structurally defined probes based on non-natural peptide-bond isosteres were thus designed. Thus, two peptide mimetics were obtained (so-called reduced amide pseudopeptides), in which naturally made amide bonds of the (30)FIN(32)-binding motif of MSA-2 were replaced with ψ-[CH2-NH] methylene amide isostere bonds, one between the F-I and the second between I-N amino acid pairs, respectively, coded as ψ-128 ψ-130.

Protection against malaria is conferred by passive transferring rabbit F(ab)(2)' antibody fragments, induced by Plasmodium falciparum MSP-1 site-directed designed pseudopeptide-BSA conjugates assessed in a rodent model.

F(ab)(2)'-immunoglobulin (Ig) fragments induced by site-directed designed immunogens are emerging as novel tools of potential utility in the treatment of clinical episodes of transmissible diseases such as malaria. Immunogens based on reduced amide pseudopeptides based on site-directed molecular modifications represent structural probes that could be considered as novel vaccine candidates, as we have previously demonstrated. We have obtained F(ab)(2)'-Ig rabbit antibodies induced against the N-terminal sequence of the native Merozoite Surface Protein-1 (MSP-1) of Plasmodium falciparum and a set of five MSP-1-derived reduced amide pseudopeptides.

A C-terminal cationic fragment derived from an arginine-rich peptide exhibits in vitro antibacterial and anti-plasmodial activities governed by its secondary structure properties.

The differential in vitro antimicrobial activity of a 12-residue-long arginine-rich peptide derived from protamine was examined against bacterial and parasite microbes. A design of discrete peptide fragments based on the thermolysin-digestion map allowed us to propose three peptide fragments to be further assessed regarding their biological and secondary structural properties. Peptide structure allowed designing three arginine-rich fragments.