Small Peptide (CEL-1000) Derived from the Beta-Chain of the Human Major Histocompatibility Complex Class II Molecule Induces Complete Protection Against Malaria in an Antigen-Independent Manner

摘要

CEL-1000 (DGQEEKAGVVSTGLIGGG) is a novel potential preventative and therapeutic agent. We report that CEL-1000 confers a high degree of protection against Plasmodium sporozoite challenge in a murine model of malaria, as shown by the total absence of blood stage infection following challenge with 100 sporozoites (100% protection) and by a substantial reduction (400-fold) of liver stage parasite RNA following challenge with 50,000 sporozoites. CEL-1000 protection was demonstrated in A/J (H-2a) and C3H/HeJ (H-2k) mice but not in BALB/c (H-2d) or CAF1 (A/J BALB/c F1 hybrid) mice. In CEL-1000-treated and protected mice, high levels of gamma interferon (IFN- ) in serum and elevated frequencies of hepatic and splenic CD4 IFN- - positive T cells were detected 24 h after administration of an additional dose of CEL-1000. Treatment of A/J mice that received CEL-1000 with antibodies against IFN- just prior to challenge abolished the protection, and a similar treatment with antibodies against CD4 T cells partially reduced the level of protection, while treatment with control antibodies or antibodies specific for interleukin-12 (IL-12), CD8 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.