Rapid identification of malaria vaccine candidates based on alpha-helical coiled coil protein motif.
To identify malaria antigens for vaccine development, we selected alpha-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 alpha-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.
Villard
Viviane
V
Department of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Agak
George W
GW
Frank
Géraldine
G
Jafarshad
Ali
A
Servis
Catherine
C
Nébié
Issa
I
Sirima
Sodiomon B
SB
Felger
Ingrid
I
Arevalo-Herrera
Myriam
M
Herrera
Socrates
S
Heitz
Frederic
F
Bäcker
Volker
V
Druilhe
Pierre
P
Kajava
Andrey V
AV
Corradin
Giampietro
G
D000818:Animals; D000913:Antibodies, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D016678:Genome; D006801:Humans; D017780:Malaria Vaccines / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D010961:Plasmodium / Q000235:genetics*; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics
D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010446:Peptide Fragments; D010455:Peptides; D015800:Protozoan Proteins