Innate-immunity cytokines induced by very small size proteoliposomes, a Neisseria-derived immunological adjuvant

2007 
Summary Neisserial outer membrane proteins have been combined with monosialogan- glioside GM3 to form very small size proteoliposomes (VSSP),a nanoparticu- lated formulation used as a cancer vaccine for the treatment of cancer patients with GM3-positive tumours. VSSP were shown to elicit anti-GM3 and anti- tumour immune responses. VSSP have also been shown to be an efficient adjuvant for tumour-cell and peptide-antigen vaccines in mice. In vitro studies showed that VSSP promote maturation of both murine and human dendritic cells, suggesting that VSSP could be used as efficient adjuvants. In order to study further the capacity of VSSP to elicit innate immune responses, human peripheral blood mononuclear cells and monocytes derived thereof were assessed for in vitro secretion of interleukin (IL)-10, IL-6, IL-12 and interferon (IFN)-g. VSSP most prominently induced the secretion of IL-6. IL-10 was secreted at a lower level. IL-12 p40 (but no p70) was also detected. IFN-gresponse was observed in 56% of the tested samples.Cytokine secretion was not related to lipopolysaccharide (LPS) content and involved Toll-like receptor 2 (TLR2)-mediated signal transduction. VSSP also induced DC maturation and a cytokine secretion pattern (high IL-6/low IL-10) which differs from that induced by LPS. The observed proinflammatory cytokine secretion pattern and the capacity of VSSP to drive DC maturation are exam- inedinthelightof thepropertiesof otherbacterialderivativescurrentlybeing user for immunotherapy purposes. Our results suggest that VSSP could be tested in clinical settings where T helper 1-type immune responses would be beneficial.
    • Correction
    • Source
    • Cite
    • Save
    • Machine Reading By IdeaReader
    61
    References
    9
    Citations
    NaN
    KQI
    []