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Publication Detail
Lentiviral vaccination does not require direct transduction of cDC
  • Publication Type:
    Conference
  • Authors:
    Goold H, Escors D, Chakraverty R, Bennett C
  • Name of conference:
    Dendritic cells Keystone symposium
  • Conference place:
    Banff, Canada
  • Conference start date:
    29/03/2009
  • Conference finish date:
    03/04/2009
Abstract
Lentiviral vectors are potent vaccination vehicles for delivery of antigens for immunotherapy. Cutaneous immunisation with lentivectors results in prolonged presentation of lentiviral antigen for at least 3 weeks post-vaccination. Putative skin-derived DC from draining LN have been shown to present lentiviral antigen 2 days after immunisation (He et al (2006) Immunity 24: 643), and the detection of transgenic antigen expression by these cells has lead to the conclusion that the potency of lentiviral immunisation is partly due to direct transduction of priming DC. However, the source of the persistent lentiviral antigen is not known, nor whether directly transduced DC are required to prime the effector T cell response. Conventional DC (cDC) are efficiently depleted from CD11c-DTR mice, but repopulation in LN and spleen is evident within 72 hours of injection of diphtheria toxin (DT). Generation of CD11c-DTR syngeneic bone marrow chimeras allows prolonged depletion of cDC by repeated injections of DT. Depletion of cDC prior to, and for 5 days following, cutaneous immunisation with Lenti-Ovalbumin ablates presentation to antigen-specific T cells. However, effector CTL responses on day 9 are unaffected in cDC-depleted mice. We hypothesised that cDC repopulating the skin and draining LN between days 5 and 9 were sufficient to process and present lentiviral antigen, and to prime effector T cell function. In support of this hypothesis, extended DT treatment throughout the time course of the experiment abrogates the CTL response. These data suggest that the efficacy of cutaneous lentiviral vaccination does not depend on direct transduction of cDC, but that DC differentiating post-immunisation can efficiently process and present lentiviral antigen from transduced cells.
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