A small peptide (CEL-1000) derived from the β-chain of the human major histocompatibility complex class II molecule induces complete protection against malaria in an antigen-independent manner

Charoenvit, Yupin, Brice, Gary T., Bacon, David, Majam, Victoria, Williams, Jackie, Abot, Esteban, Ganeshan, Harini, Sedegah, Martha, Doolan, Denise L., Carucci, Daniel J., and Zimmerman, Daniel H. (2004) A small peptide (CEL-1000) derived from the β-chain of the human major histocompatibility complex class II molecule induces complete protection against malaria in an antigen-independent manner. Antimicrobial Agents and Chemotherapy, 48 (7). pp. 2455-2463.

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Abstract

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-γ) in serum and elevated frequencies of hepatic and splenic CD4⁺ IFN-γ-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-γ 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-γ 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.

Item ID: 42753
Item Type: Article (Refereed Research - C1)
ISSN: 1098-6596
Funders: Naval Medical Research Centre (NMRC), CEL-SCI Corporation
Projects and Grants: NMRC 6000.RAD1.F.A0309, CEL-SCI NCRADA NMRC-96-NMR-500
Date Deposited: 22 Mar 2016 22:40
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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