CpG oligodeoxynucleotide augments HSV-2 glycoprotein D DNA vaccine efficacy to generate T helper 1 response and subsequent protection against primary genital herpes infection in mice

Abstract

The present study was undertaken to evaluate the efficacy of a combined use of DNA vaccine of HSV-2 glycoprotein D (gD DNA) and CpG oligodeoxynucleotide (ODN) in comparison to gD DNA vaccine alone in inducing immunity against genital HSV-2 infection. Intramuscular vaccination of C57Bl/6 mice with gD DNA followed 48 h later by CpG ODN administration conferred a strong immunity against genital herpes infection. This was concomitant with development of a robust specific IgG2c (an indicator of Th1-type response in C57Bl/6 mice) antibody response as well as IFN-γ production by genital lymph node and spleen cells in vitro. Administration of CpG ODN prior to gD DNA immunization, on the other hand, was inferior to immunization with gD DNA alone in providing protection against macroscopic signs of the disease. Consistent with the in vivo protection data, mice immunized with CpG ODN followed by gD DNA vaccine showed decreased specific lymphoproliferative and IFN-γ responses compared to gD DNA vaccinated mice. In conclusion, these results indicate that timely administration of CpG ODN augments the immunity elicited by gD DNA vaccine, resulting in augmented Th1-type immunity against genital herpes infection in mice. These findings emphasize the value of using CpG ODN in a DNA vaccination scheme against genital herpes and merit also further evaluation in genetic vaccination approaches against other sexually transmitted infections.