CD4(+) T-cell- and gamma interferon-dependent protection against murine malaria by immunization with linear synthetic peptides from a Plasmodium yoelii 17-kilodalton hepatocyte erythrocyte protein

Most work on protective immunity against the pre-erythrocytic stages of mal aria has focused on induction of antibodies that prevent sporozoite invasio n of hepatocytes, and CD8(+) T-cell responses that eliminate infected hepat ocytes. We recently reported that immunization of A/J mice with an 18-amino -acid synthetic linear peptide from Plasmodium yoelii sporozoite surface pr otein 2 (SSP2) in TiterMax adjuvant induces sterile protection that is depe ndent on CD4(+) T cells and gamma interferon (IFN-gamma). We now report tha t immunization of inbred A/J mice and outbred CD1 mice with each of two lin ear synthetic peptides from the 17-kDa P. yoelii hepatocyte erythrocyte pro tein (HEP17) in the same adjuvant also induces protection against sporozoit e challenge that is dependent on CD4(+) T cells and IFN-gamma. The SSP2 pep tide and the two HEP17 peptides are recognized by B cells as well as T cell s, and the protection induced by these peptides appears to be directed agai nst the infected hepatocytes, In contrast to the peptide-induced protection , immunization of eight different strains of mice with radiation-attenuated sporozoites induces protection that is absolutely dependent on CD8(+) T ce lls. Data represented here demonstrate that CD4(+) T-cell-dependent protect ion fan be induced by immunization with linear synthetic peptides. These st udies therefore provide the foundation for an approach to pre-erythrocytic- stage malaria vaccine development, based on the induction of protective CD4 (+) T-cell responses, which mill complement efforts to induce protective an tibody and CD8(+) T-cell responses.