Rapid Identification of Malaria Vaccine Candidates Based on α-Helical Coiled Coil Protein Motif

Viviane Villard,Ali Jafarshad,Sodiomon B Sirima,George W Agak,Socrates Herrera,Frederic Heitz,Andrey V Kajava,Ingrid Felger,Giampietro Corradin,Volker Bäcker,Géraldine Frank,Catherine Servis,Issa Nébié,Myriam Arevalo-Herrera,Pierre Druilhe

doi:10.1371/journal.pone.0000645

Abstract

To identify malaria antigens for vaccine development, we selected α-helical coiled coil domains of proteins predicted to be present in the parasite erythrocytic stage. The corresponding synthetic peptides are expected to mimic structurally “native” epitopes. Indeed the 95 chemically synthesized peptides were all specifically recognized by human immune sera, though at various prevalence. Peptide specific antibodies were obtained both by affinity-purification from malaria immune sera and by immunization of mice. These antibodies did not show significant cross reactions, i.e., they were specific for the original peptide, reacted with native parasite proteins in infected erythrocytes and several were active in inhibiting in vitro parasite growth. Circular dichroism studies indicated that the selected peptides assumed partial or high α-helical content. Thus, we demonstrate that the bioinformatics/chemical synthesis approach described here can lead to the rapid identification of molecules which target biologically active antibodies, thus identifying suitable vaccine candidates. This strategy can be, in principle, extended to vaccine discovery in a wide range of other pathogens.

Highlights

Human Plasmodium falciparum (Pf) infection is a dramatic public health problem
We focused on the search for a-helical coiled coil motifs that, in general, do not exhibit a folding problem, and are a target of effective antibodies for several current malaria vaccine candidates
To test the biological activity of peptide-specific antibodies, the latter were purified by affinity chromatography using three serum pools obtained from Papua New Guinean adults

Summary

Introduction

Human Plasmodium falciparum (Pf) infection is a dramatic public health problem. Today approximately forty percent of the world’s population is at risk of malaria. We focused on the search for a-helical coiled coil motifs that, in general, do not exhibit a folding problem, and are a target of effective antibodies for several current malaria vaccine candidates Longer peptides (up to 70 amino acids), which contained one or more a-helical coiled coil domains, were synthesized

Results

Conclusion