In vivo modulation of vaccine-induced immune responses toward a Th1 phenotype increases potency and vaccine effectiveness in a herpes simplex virus type 2 mouse model

Several vaccines have been investigated experimentally in the herpes simple x virus type 2 (HSV-2) model system. While it is believed that CD4(+)-T-cel l responses are important for protection in general, the correlates of prot ection from HSV3 infection are still under investigation, Recently, the use of molecular adjuvants to drive vaccine responses induced by DNA vaccines has been reported in a number of experimental systems. We sought to take ad vantage of this immunization model to gain insight into the correlates of i mmune protection in the HSV-2 mouse model system and to further explore DNA vaccine technology. To investigate whether the Th1- or Th2-type immune res ponses are more important for protection from HSV-2 infection, we codeliver ed the DNA expression construct encoding the HSV-2, go protein with the gen e plasmids encoding the Th1-type (interleukin-2 [IL-2], IL-12, IL-15, and I L-18) and Th2-type (IL-4 and IL-10) cytokines in an effort to drive immunit y induced by vaccination. We then analyzed the modulatory effects of the va ccine on the resulting immune phenotype and on the mortality and the morbid ity of the immunized animals following a lethal challenge with HSV-2, We ob served that Th1 cytokine gene coadministration not only enhanced the surviv al rate but also reduced the frequency and severity of herpetic lesions fol lowing intravaginal HSV challenge. On the other hand, coinjection with Th2 cytokine genes increased the rate of mortality and morbidity of the challen ged mice. Moreover, of the Th1-type cytokine genes tested, IL-12 was a part icularly potent adjuvant for the gD DNA vaccination.