PROTECTION AGAINST MALARIA BY PLASMODIUM-YOELII SPOROZOITE SURFACE PROTEIN-2 LINEAR PEPTIDE INDUCTION OF CD4(-CELL-DEPENDENT AND IFN-GAMMA-DEPENDENT ELIMINATION OF INFECTED HEPATOCYTES() T)

Plasmodium falciparum sporozoite surface protein 2 (SSP2), also known as TRAP, is included in experimental human malaria vaccines because Pl asmodium yoelii SSP2 is the target of protective CD8(+) CTL that elimi nate P. yoelii-infected hepatocytes in mice, We now report that immuni zation with a synthetic branched-chain peptide including four copies o f a PySSPZ sequence, NPNEPS, and two tetanus toxin T helper epitopes i n the adjuvant TiterMax, or with an 18 amino acid peptide (NPNEPS), in the adjuvant protects A/J, but not BALB/c or C57BL/6 mice, Transfer o f T lymphocyte-enriched immune splenocytes protects naive mice; in viv o depletion of CD4(+) T cells eliminates vaccine-induced protection; a nd in vivo treatment with anti-IFN-gamma reverses vaccine-induced acti vity against infected hepatocytes, Lymph node cells from immunized A/J , BALB/c, and C57BL/6 mice recognize the (NPNEPS), peptide in vitro, H owever, the protected A/J mice respond with a predominantly Th1 patter n of lymphocyte response, and the non-protected strains of mice respon d with a Th2 pattern, There are many examples of CD4(+) T cells transf erring protection against infectious organisms, However, to our knowle dge, this is the first formal demonstration that immunization with a l inear synthetic peptide induces CD4(+) T cell-dependent, IFN-gamma dep endent, genetically restricted sterile protective immunity against an infectious agent.