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 gen erated using solid-phase peptide synthesis. The immunological and protectiv e properties of peptide PbCS 242-310 were studied in BALB/c mice (H-2(d)). Two subcutaneous injections, in the presence of IFA at the base of the tail , generated (i) high titers of anti-peptide antibodies which also recognize d the native P. berghei CS protein, (ii) cytolytic T cells specific for the K-d-restricted peptide PbCS 245-253 and (iii) partial CD8(+)-dependent pro tection against sporozoite-induced malaria. The same frequencies of peptide PbCS 245-253 specific CD8(+) T cells were found by IFN-gamma ELISPOT in th e draining lymph nodes of animals immunized with the short optimal CTL pept ide 245-253 or with the polypeptide 242-310, indicating that the longer pol ypeptide 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 f our 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 conco mitant protection.