VACCINATION OF MICE WITH HERPES-SIMPLEX VIRUS TYPE-1 GLYCOPROTEIN-D DNA PRODUCES LOW-LEVELS OF PROTECTION AGAINST LETHAL HSV-1 CHALLENGE

The herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) gene was i nserted into vectors pSVL or pRc/CMV under control of the SV40 late pr omoter or the human cytomegalovirus major immediate-early promoter, re spectively. Intramuscular injection of mice with these go-containing p lasmids appeared to induce low levels of serum anti-go antibody, as ju dged by the appearance of low levels of anti-HSV-1-neutralizing antibo dy and anti go ELISA responses in the serum of gD-DNA-vaccinated mice. As previously reported in other virus systems, vaccination with vecto r DNA also induced ELISA and neutralizing antibody titers, However, th ese 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, si nce serum from mice vaccinated with plasmid-gD immunoprecipitated sign ificant amounts of go from extracts of HSV-1-infected cells, while ser um from mice vaccinated with vectors was unable to immunoprecipitate g o or any other obvious HSV-1 proteins. Neither psVL-gD nor pRc/CMV-gD induced detectable lymphocyte proliferative or CTL responses. Vaccinat ion with pSVL-gD provided a significant (P = 0.04, Fisher's exact test ), but low level of protection against lethal challenge with HSV-1. Va ccination with pRc/CMV-gD also appeared to provide a low level of prot ection against challenge, that was statistically significance at the 1 0% level (P = 0.054, Fisher's exact test). Reports from numerous labor atories (including ours) have shown that vaccination with recombinantl y expressed go can provide very high levels of protection against HSV- 1 lethal challenge. Thus, the results reported here suggest that vacci nation with HSV-1 gD-DNA is not yet a useful alternative to a go subun it vaccine.