CEL-1000 (DGQEEKAGVVSTGLIGGG) is a novel potential preventative and therapeutic agent. We report that CEL-1000 confers a high degree of protection against؉ T cells, or NK cells had no effect. Our data establish that the protection induced by CEL-1000 is dependent on IFN-␥ and is partially dependent on CD4 ؉ T cells but is independent of CD8 ؉ T cells, NK cells, and IL-12 at the effector phase and does not induce a detectable antibody response.Malaria remains a major cause of mortality and morbidity in tropical and subtropical areas of the world, with approximately 300 million people considered at risk of infection. Although several clinical malaria vaccines have been developed and are being evaluated for their protective efficacies (for a review, see reference 19), prophylaxis and treatment with antimalarial drugs remain the only options for effective malaria control. In recent years, drug-resistant parasites have emerged and are now widespread, presenting serious problems for malaria control. Therefore, new and effective antimalarial interventions, both drugs and vaccines, are needed. It was previously demonstrated (3) that immunization with linear synthetic peptides containing B-and T-cell epitopes derived from the Plasmodium yoelii 17-kDa hepatocyte-erythrocyte protein (PyHEP17) protected A/J and CD1 mice but not BALB/c or C57BL/6 mice against sporozoite challenge, and this protection was dependent on CD4 ϩ T cells and gamma interferon (IFN-␥) but not on CD8 ϩ T cells. The protected mice displayed a Th1-type antibody profile (immunoglobulin G2a [IgG2a]), while the nonprotected mice displayed a predominant Th2-type antibody profile (IgG1).The ligand epitope antigen presentation system technology came out of our efforts to direct the immune response toward a Th1 or Th2 orientation for a synthetic peptide vaccine. Immunization of mice with a Mycobacterium antigen conjugated to various T-cell binding ligands (TCBLs) induced either Th1-or Th2-type antibody responses to the native epitope of the 38-kDa protein of Mycobacterium tuberculosis, depending upon the TCBL used (26). The TCBL peptides have been shown to enhance the immunogenicities of antigenic epitopes, activate T cells, and direct the immune response to either a Th1-type antibody by use of a peptide (referred to as peptide J) from -2 microglobulin or a Th2-type antibody by use of a peptide (referred to as peptide G) from the  chain of the major histocompatibility complex (MHC) class II (MHC-II) molecule and the immunogens (20,26,27). In other studies with the herpes simplex virus (HSV) model, heteroconjugate vaccines containing a T-cell epitope from HSV type 1 (HSV-1) glycoprotein D and peptide J as the TCBLs have been shown to elicit Th1-type responses and protection against HSV-1 challenge (5, 20). More recently, using a modified G called derG (the peptide that has now been renamed CEL-1000), we observed that, in contrast to the TCBL peptide G, CEL-1000 induced a human immunodeficiency virus Gag protein Th1-type antibody profile (IgG2a), with very low...