In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 48, No. 7 ( 2004-07), p. 2455-2463
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 - 2 a ) and C3H/HeJ ( H - 2 k ) mice but not in BALB/c ( H - 2 d ) or CAF1 (A/J × BALB/c F 1 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.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.48.7.2455-2463.2004
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2004
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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