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
[1] Sato et al Science Vol. 273 pp. 352-354
[2] Krieg et al PNAS Vol. 95 pp. 12631-12636
