The synthetic, oxidized C-terminal fragment of the Plasmodium berghei circumsporozoite protein elicits a high protective response.
A polypeptide of 69 amino acids (PbCS 242-310) encompassing the C-terminal region of the circumsporozoite protein of Plasmodium berghei (PbCS) was generated using solid-phase peptide synthesis. The immunological and protective properties of peptide PbCS 242-310 were studied in BALB/c mice (H-2d). Two subcutaneous injections, in the presence of IFA at the base of the tail, generated (i) high titers of anti-peptide antibodies which also recognized the native P. berghei CS protein, (ii) cytolytic T cells specific for the Kd-restricted peptide PbCS 245-253 and (iii) partial CD8+-dependent protection against sporozoite-induced malaria. The same frequencies of peptide PbCS 245-253 specific CD8+ T cells were found by IFN-gamma ELISPOT in the draining lymph nodes of animals immunized with the short optimal CTL peptide 245-253 or with the polypeptide 242-310, indicating that the longer polypeptide can be processed and presented in vivo in the context of MHC class I as efficiently as the short CTL peptide. Interestingly, higher levels of IFN-gamma producing CD8 T cells and protection were observed when the four cysteine residues present in the C-terminal peptide were fully oxidized. These findings underline the potential importance of the chemical nature of the C-terminal fragment on the activation of the immune system and concomitant protection.
Roggero
M A
MA
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Meraldi
V
V
López
J A
JA
Eberl
G
G
Romero
J C
JC
Matile
H
H
Betschart
B
B
Corradin
G
G
Renggli
J
J
D000818:Animals; D005260:Female; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000276:immunology*; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D017780:Malaria Vaccines; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma