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*
Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany; and
Department of Immunology, University Clinics of Ulm, Ulm, Germany
Protective immunity against Listeria monocytogenes
strongly depends on CD8+ T lymphocytes, and both IFN-
secretion and target cell killing are considered relevant to
protection. We analyzed whether we could induce a protective type 1
immune response by DNA vaccination with the gene gun using plasmids
encoding for two immunodominant listerial Ags, listeriolysin and p60.
To induce a Th1 response, we 1) coprecipitated a plasmid encoding for
GM-CSF, 2) employed a prime/boost vaccination schedule with a 45-day
interval, and 3) coinjected oligodeoxynucleotides (ODN) containing
immunostimulatory CpG motifs. DNA immunization of BALB/c mice with
plasmids encoding for listeriolysin (pChly) and p60 (pCiap) efficiently
induced MHC class I-restricted, Ag-specific CD8+ T cells
that produced IFN-. Coinjection of CpG-ODN significantly increased
the frequency of specific IFN--secreting T cells. Although pChly
induced specific CD8+ T cells expressing CTL activity, it
failed to stimulate CD4+ T cells. Only pCiap induced
significant CD4+ T cell and humoral responses, which were
predominantly of Th2 type. Vaccination with either plasmid induced
protective immunity against listerial challenge, and coinjection of CpG
ODN improved vaccine efficacy in some situations. This study
demonstrates the feasibility of gene gun administration of plasmid DNA
for inducing immunity against an intracellular pathogen for which
protection primarily depends on type 1 CD8+ T
cells.
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