Vaccination of mice with herpes simplex virus type 1 glycoprotein D DNA produces low levels of protection against lethal HSV-1 challenge

Abstract

The herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) gene was inserted into vectors pSVL or pRc CMV under control of the SV40 late promoter or the human cytomegalovirus major immediate-early promoter, respectively. Intramuscular injection of mice with these gD-containing plasmids appeared to induce low levels of serum anti-gD antibody, as judged by the appearance of low levels of anti-HSV-1-neutralizing antibody and anti-gD ELISA responses in the serum of gD-DNA-vaccinated mice. As previously reported in other virus systems, vaccination with vector DNA also induced ELISA and neutralizing antibody titers. However, these titers were lower than those induced by the gD-containing plasmids. The ELISA and neutralization titers induced by the vectors appeared to be non-specific rather than directed at specific HSV-1 proteins, since serum from mice vaccinated with plasmid-gD immunoprecipitated significant amounts of gD from extracts of HSV-1-infected cells, while serum from mice vaccinated with vectors was unable to immunoprecipitate gD or any other obvious HSV-1 proteins. Neither pSVL-gD nor pRc CMV-gD induced detectable lymphocyte proliferative or CTL responses. Vaccination with pSVL-gD provided a significant ( P = 0.04, Fisher's exact test), but low level of protection against lethal challenge with HSV-1. Vaccination with pRc CMV-gD also appeared to provide a low level of protection against challenge, that was statistically significance at the 10% level ( P = 0.054, Fisher's exact test). Reports from numerous laboratories (including ours) have shown that vaccination with recombinantly expressed gD can provide very high levels of protection against HSV-1 lethal challenge. Thus, the results reported here suggest that vaccination with HSV-1 gD-DNA is not yet a useful alternative to a gD subunit vaccine.