In article <jsg-2107990834320001 at jsgpb1.path.cam.ac.uk>,
jsg at mole.bio.cam.ac.uk (James Good) wrote:
>> Here is a scenario on which I would value your thoughts. When I
coimmunise
> with a DNA vaccine encoding (what I believe to be) a cytosolic
antigen and
> a plasmid encoding a cytokine, I see varying degrees of suppression
of the
> IgG response to the antigen. This happens at doses of both 100µg and
10µg
> each plasmid so I don't envisage a reduction in the uptake of the DNA
> vaccine by the presence of the cytokine plasmid. One theory is that
the
> presence of extra stimulatory CpG motifs elicits interferon-g
synthesis
> which downregulates transgene expression, reducing the antibody titre
[1].
> (Another is that inhibitory CpG motifs present in the cytokine plasmid
> backbone also reduce immunogenicity [2]). But the strange thing is,
the
> cytokine plasmid encoding interferon-g is the least suppressive of
all.
> Could interferon-g expressed from the plasmid be stimulatory, but that
> induced by the presence of the DNA (ie from an endogenous promoter
rather
> than the CMV promoter driving ifn-g expression on the plasmid) be
> inhibitory? Any thoughts welcome.
>> James
You could try the experiments in IFNg knockout mice, or anti-IFN
treated mice, to address the question of endogenous IFN. Have you
tried co-immunizing with an empty vector containing the same CpG motifs
as the cytokine plasmids?
--
P. Schiff
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