Structure-activity-based design of a synthetic malaria peptide eliciting sporozoite inhibitory antibodies in a virosomal formulation.
The circumsporozoite protein (CSP) of Plasmodium falciparum is a leading candidate antigen for inclusion in a malaria subunit vaccine. We describe here the design of a conformationally constrained synthetic peptide, designated UK-39, which has structural and antigenic similarity to the NPNA-repeat region of native CSP. NMR studies on the antigen support the presence of helical turn-like structures within consecutive NPNA motifs in aqueous solution. Intramuscular delivery of UK-39 to mice and rabbits on the surface of reconstituted influenza virosomes elicited high titers of sporozoite crossreactive antibodies. Influenza virus proteins were crucially important for the immunostimulatory activity of the virosome-based antigen delivery system, as a liposomal formulation of UK-39 was not immunogenic. IgG antibodies elicited by UK-39 inhibited invasion of hepatocytes by P. falciparum sporozoites, but not by antigenically distinct P. yoelii sporozoites. Our approach to optimized virosome-formulated synthetic peptide vaccines should be generally applicable for other infectious and noninfectious diseases.
Okitsu
Shinji L
SL
Molecular Immunology, Swiss Tropical Institute, CH-4002 Basel, Switzerland.
Kienzl
Ursula
U
Moehle
Kerstin
K
Silvie
Olivier
O
Peduzzi
Elisabetta
E
Mueller
Markus S
MS
Sauerwein
Robert W
RW
Matile
Hugues
H
Zurbriggen
Rinaldo
R
Mazier
Dominique
D
Robinson
John A
JA
Pluschke
Gerd
G
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000276:immunology*; D002626:Chemistry, Pharmaceutical; D003429:Cross Reactions; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006825:Hybridomas / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D017780:Malaria Vaccines / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D010967:Plasmodium yoelii / Q000276:immunology / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D022701:Virosomes / Q000737:chemistry*
D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010714:Phosphatidylethanolamines; D015800:Protozoan Proteins; D022701:Virosomes; C041595:circumsporozoite protein, Protozoan