[Effect of tumor necrosis factor DNA on immune response to DNA immunization against herpes simplex virus].
A study was made of the adjuvant effect of the mouse tumor necrosis factor alpha (mTNF alpha) on DNA immunization against the herpes simplex virus type 1 (HSV1). The HSV1 gD gene (pDNAgD) served as an immunogen; mTNF alpha or its gene cloned in an eukaryotic expression vector (pDNAmTNF) were used to modulate the immune response. Double immunization with pDNAgD led to a sixfold increase in the in vitro T-cell response, a high (1:2000) titer of anti-HSV1 antibodies (including virus-neutralizing antibodies), an increase in IgG2a/IgG1 (suggesting a shift of the immune response to the Th1 type), and no change in CD4/CD8 T-cell ratio. A single injection of mTNF alpha along with inactivated HSV1 allowed a twice higher antibody titer and a fourfold higher T-cell response as compared with immunization with HSV1 alone. Double immunization with both pDNAgD and pDNAmTNF increased the titer of anti-HSV1 antibodies and the T-cell response by factors of 8 and 1.5, respectively, as compared with immunization with pDNAgD alone. However, the protective effect was significantly lower with the two plasmids than with pDNAgD (73 vs. 100%). Thus, DNA immunization with pDNAgD induced both B- and T-cell responses and completely protected mice from a lethal doze of HSV1. The adjuvant properties of mTNF alpha and pDNAmTNF need further investigation.
Klimova
R R
RR
Ivanovsky Institute of Virology, Russian Academy of Medical Sciences, Moscow, 123098 Russia.
Kozlov
A Iu
AIu
Shingarova
L N
LN
Nekrasova
O V
OV
Boldyreva
E F
EF
Guseva
T S
TS
Parshina
O V
OV
Malinovskaia
V V
VV
Novikov
V V
VV
Kushch
A A
AA
D000914:Antibodies, Viral / Q000096:biosynthesis; D001483:Base Sequence; D004247:DNA / Q000276:immunology*; D017931:DNA Primers; D007111:Immunity, Cellular; D018139:Simplexvirus / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D019444:Vaccines, DNA / Q000276:immunology*
D000914:Antibodies, Viral; D017931:DNA Primers; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D004247:DNA