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*
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden; and
Neuroimmunology Unit, Center for Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
We here study the adjuvant properties of immunostimulatory DNA
sequences (ISS) and coinjected cytokine-coding cDNA in suppressive
vaccination with DNA encoding an autoantigenic peptide, myelin basic
protein peptide 68–85, against Lewis rat experimental autoimmune
encephalomyelitis (EAE). EAE is an autoaggressive, T1-mediated disease
of the CNS. ISS are unmethylated CpG motifs found in bacterial DNA,
which can induce production of type 1 cytokines in vertebrates through
the innate immune system. Because ISS in the plasmid backbone are
necessary for efficient DNA vaccination, we studied the effect of one
such ISS, the 5'-AACGTT-3' motif, in our system. Treatment with a DNA
vaccine encoding myelin basic protein peptide 68–85 and containing
three ISS of 5'-AACGTT-3' sequence suppressed clinical signs of EAE,
while a corresponding DNA vaccine without such ISS had no effect. We
further observed reduced proliferative T cell responses in rats treated
with the ISS-containing DNA vaccine, compared with controls. We also
studied the possible impact of coinjection of plasmid DNA encoding rat
cytokines IL-4, IL-10, GM-CSF, and TNF-
with the ISS-containing DNA
vaccine. Coinjection of IL-4-, IL-10-, or TNF--coding cDNA inhibited
the suppressive effect of the DNA vaccine on EAE, whereas GM-CSF-coding
cDNA had no effect. Coinjection of cytokine-coding cDNA with the
ISS-deficient DNA vaccine failed to alter clinical signs of EAE. We
conclude that the presence of ISS and induction of a local T1 cytokine
milieu is decisive for specific protective DNA vaccination in
EAE.
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