Antibodies elicited by a virosomally formulated Plasmodium falciparum serine repeat antigen-5 derived peptide detect the processed 47 kDa fragment both in sporozoites and merozoites.
Serine repeat antigen-5 (SERA5) is a candidate antigen for inclusion into a malaria subunit vaccine. During merozoite release and reinvasion the 120 kDa SERA5 precursor protein (P120) is processed, and a complex consisting of an N-terminal 47 kDa (P47) and a C-terminal 18kDa (P18) processing product associates with the surface of merozoites. This complex is thought to be involved in merozoite invasion of and/or egress from host erythrocytes. Here we describe the synthesis and immunogenic properties of virosomally formulated synthetic phosphatidylethanolamine (PE)-peptide conjugates, incorporating amino acid sequence stretches from the N-terminus of Plasmodium falciparum SERA5. Choosing an appropriate sequence was crucial for the development of a peptide that elicited high titers of parasite cross-reactive antibodies in mice. Monoclonal antibodies (mAbs) raised against the optimized peptide FB-23 incorporating amino acids 57-94 of SERA5 bound to both P120 and to P47. Western blotting analysis proved for the first time the presence of SERA5 P47 in sporozoites. In immunofluorescence assays, the mAbs stained SERA5 in all its predicted localizations. The virosomal formulation of peptide FB-23 is suitable for use in humans and represents a candidate component for a multi-valent malaria subunit vaccine targeting both sporozoites and blood stage parasites.
Okitsu
Shinji L
SL
Molecular Immunology, Swiss Tropical Institute, CH-4002 Basel, Switzerland.
Boato
Francesca
F
Mueller
Markus S
MS
Li
Dong Bo
DB
Vogel
Denise
D
Westerfeld
Nicole
N
Zurbriggen
Rinaldo
R
Robinson
John A
JA
Pluschke
Gerd
G
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D017780:Malaria Vaccines / Q000276:immunology; D052940:Merozoites / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D034101:Sporozoites / Q000737:chemistry*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; C480167:serine repeat antigen 5, Plasmodium falciparum