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Antimicrobial Agents and Chemotherapy, July 2004, p. 2455-2463, Vol. 48, No. 7
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.7.2455-2463.2004

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

Malaria Program, Naval Medical Research Center,¹ Department of Entomology, Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910-7500,³ Henry M. Jackson Foundation, Rockville, Maryland 20852,² Department of Molecular Microbiology and Immunology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205,⁴ CEL-SCI Corporation, Vienna, Virginia 22182⁵

Received 4 September 2003/ Returned for modification 9 January 2004/ Accepted 17 March 2004

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-2^a) and C3H/HeJ (H-2^k) mice but not in BALB/c (H-2^d) or CAF1 (A/J x 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.