J. Fensterle et al., Effective DNA vaccination against listeriosis by prime/boost inoculation with the gene gun, J IMMUNOL, 163(8), 1999, pp. 4510-4518
Protective immunity against Listeria monocytogenes strongly depends on CD8(
+) T lymphocytes, and both IFN-gamma secretion and target cell killing are
considered relevant to protection. We analyzed whether se could induce a pr
otective type 1 immune response by DNA vaccination with the gene gun using
plasmids encoding for two immunodominant listerial Ags, listeriolysin and p
60. To induce a Th1 response, we 1) coprecipitated a plasmid encoding for G
M-CSP, 2) employed a prime/boost vaccination schedule with a 45-day interva
l, and 3) coinjected oligodeoxynucleotides (ODN) containing immunostimulato
ry CpG motifs. DNA immunization of BALB/c mice with plasmids encoding for l
isteriolysin (pChly) and p60 (pCiap) efficiently induced MHC class I-restri
cted, Ag-specific CD8(+) T cells that produced IFN-gamma. Coinjection of Cp
G-ODN significantly increased the frequency of specific IFN-gamma-secreting
T cells. Although pChly induced specific CD8(+) T cells expressing CTL act
ivity, it failed to stimulate CD4(+) T cells. Only pCiap induced significan
t CD4+ T cell and humoral responses, which were predominantly of Th2 type.
Vaccination with either plasmid induced protective immunity against listeri
al challenge, and coinjection of CpG ODN improved vaccine efficacy in some
situations. This study demonstrates the feasibility of gene gun administrat
ion of plasmid DNA for inducing immunity against an intracellular pathogen
for which protection primarily depends on type 1 CD8(+) T cells.