The Effect of the Tumor Necrosis Factor DNA on the Immune Response in DNA Immunization against the Herpes Simplex Virus |
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Authors: | Klimova R R Kozlov A Yu Shingarova L N Nekrasova O V Boldyreva E F Guseva T S Parshina O V Malinovskaya V V Novikov V V Kushch A A |
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Institution: | (1) Russian Academy of Medical Sciences, Ivanovsky Institute of Virology, Moscow, 123098, Russia;(2) Nizhni Novgorod State University, Nizhni Novgorod, 603600, Russia;(3) Russian Academy of Sciences, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997, Russia;(4) Russian Academy of Medical Sciences, Gamaleya Institute of Epidemiology and Microbiology, Moscow, 123098, Russia;(5) Nizhni Novgorod State University, Nizhni Novgorod, 603600, Russia |
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Abstract: | A study was made of the adjuvant effect of the mouse tumor necrosis factor (mTNF ) on DNA immunization against the herpes simplex virus type 1 (HSV1). The HSV1 gD gene (pDNAgD) served as an immunogen; mTNF 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 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 and pDNAmTNF need further investigation. |
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Keywords: | mouse tumor necrosis factor DNA immunization herpes simplex virus type 1 anti-HSV1 antibodies T-cell response protective effect |
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