CD8(+) T-CELL PROTECTIVE IMMUNITY INDUCED BY IMMUNIZATION WITH PLASMODIUM-BERGHEI CS PROTEIN-DERIVED SYNTHETIC PEPTIDES - EVIDENCE THAT LOCALIZATION OF PEPTIDE-SPECIFIC CTLS IS CRUCIAL FOR PROTECTION AGAINST MALARIA

Immunization of BALB/c mice (H-2(d)) with a mixture of major histocompatibility complex (MHC) class I- and MHC class II-restricted synthetic peptides emulsified in incomplete Freund's adjuvant (IFA) induced a high level of specific cytotoxic T lymphocyte (CTL) activity. Peptides 249-260 or 252-260, derived from the circumsporozoite protein of Plasmodium berghei and representing a H-2K(d)-restricted CTL epitope, were injected twice subcutaneously or intraperitoneally in BALB/c mice in combination with the tetanus toxin-derived universal T-helper peptide P30 in IFA. No protection was observed after exposure of immunized mice to infected mosquitoes. In contrast, when peptide 252-260-specific CTLs were expanded in vitro and adoptively transferred into naive recipient, mice were partially protected (64%) against a subsequent sporozoite challenge. Furthermore, direct transfer of lymph nodes or spleen cells from mice immunized with the peptide PbCS 252-260 also conferred protection to recipient mice. This protection was long-lasting and similar to that obtained with irradiated sporozoites. Taken together, these results suggest that peptide immunization induces a qualitatively adequate CTL response which potentially can protect against malaria. However, it seems that protection can only be achieved if the migration of the CTLs is artificially induced by adoptive cell transfer. Thus, migration of specific CTLs to the liver, which might be crucial for protection against the parasite, does not seem to occur efficiently in peptide immunized mice.