Herpes Simplex Virus 2 (Hsv-2) Infected Cell Proteins Are Among The Most Dominant Antigens Of A Live-Attenuated Hsv-2 Vaccine

Virion glycoproteins such as glycoprotein D (gD) are believed to be the dominant antigens of herpes simplex virus 2 (HSV-2). We have observed that mice immunized with a live HSV-2 ICP0(-) mutant virus, HSV-2 0 Delta NLS, are 10 to 100 times better protected against genital herpes than mice immunized with a HSV-2 gD subunit vaccine (PLoS ONE 6:e17748). In light of these results, we sought to determine which viral proteins were the dominant antibody- generators (antigens) of the live HSV-2 0 Delta NLS vaccine. Western blot analyses indicated the live HSV-2 0 Delta NLS vaccine elicited an IgG antibody response against 9 or more viral proteins. Many antibodies were directed against infected-cell proteins of > 100 kDa in size, and only 10 +/- 5% of antibodies were directed against gD. Immunoprecipitation (IP) of total HSV-2 antigen with 0 Delta NLS antiserum pulled down 19 viral proteins. Mass spectrometry suggested 44% of immunoprecipitated viral peptides were derived from two HSV-2 infected cells proteins, RR-1 and ICP8, whereas only 14% of immunoprecipitated peptides were derived from HSV-2's thirteen glycoproteins. Collectively, the results suggest the immune response to the live HSV-2 0 Delta NLS vaccine includes antibodies specific for infected cell proteins, capsid proteins, tegument proteins, and glycoproteins. This increased breadth of antibody-generating proteins may contribute to the live HSV-2 vaccine's capacity to elicit superior protection against genital herpes relative to a gD subunit vaccine.