Herpes Simplex Virus Type-2 Glycoprotein-Subunit Vaccine: Tolerance and Humoral and Cellular Responses in Humans

Abstract

Twenty-three subjects were administered three doses of inactivated herpes simplex virus (HSV) type 2 (HSV-2) glycoprotein-subunit vaccine, with doses 2 and 3 being given four and 22 weeks after dose 1. Both HSV-neutralizing antibody and antibody effective in antibody-dependent cell-mediated cytotoxicity were detected in serum samples of 12 of the 13 initially seronegative subjects by week 8. The geometric mean titers of both antibody types decreased between weeks 8 and 22 but increased one week after dose 3. HSV-neutralizing antibody remained detectable in serum samples of seven of the 10 initially seronegative subjects assayed seven months after dose 3. Cell-mediated immunity was detected by lymphocyte transformation responses to HSV-2 after vaccine administration in 12 of the 13 initially seronegative subjects. Unlike humoral antibody, which waned over time, in vitro cell-mediated immune responses remained stable over the seven-month follow-up period after dose 3. This HSV-2-subunit vaccine is well tolerated and elicits both humoral and cell-mediated immune responses to HSV.

Immunity in strain 2 guinea-pigs inoculated with vaccinia virus recombinants expressing varicella-zoster virus glycoproteins I, IV, V or the protein product of the immediate early gene 62

“…Our experiments comparing vac-gpI and vac-IE-62 with the corresponding immunoaffinity-purified proteins indicate that immunity to these proteins produced by recombinant vaccinia virus, which involves de novo protein synthesis and antigen presentation occurring in infected host cells, was equivalent to the humoral and cell-mediated immunity elicited by relatively high concentrations of purified gpI or IE-62. Purified preparations of HSV and cytomegalovirus glycoproteins have also been shown to induce virus-specific antibodies and T lymphocyte proliferation (Mertz et aL, 1984;Berman et al, 1985;G6ncz61 et al, 1986;Meignier et al, 1987, Stanberry et al, 1987Bernstein et al, 1988). Nevertheless, the production of purified proteins in sufficient quantity can be difficult and protein vaccines must incorporate adjuvants that are safe for human use.…”

Immunological memory to herpes simplex virus type 1 glycoproteins B and D in mice

“…However, it is certainly the most protective HSV protein isolated and tested to date, as shown by using synthetic gD peptides (Eisenberg et al, 1985), purified gD from mammalian cell lines (Berman et al, 1985;Long et al, 1984;Sanchez-Pescador et al, 1988), vaccinia virus recombinants expressing gD (Cremer et al, 1985;Paoletti et al, 1984) or baculovirus recombinants expressing gD (Krishna et al, 1989) in both na'~ve mice and guinea-pigs. However, gD alone has not been used as a vaccine in man although it is a constituent of the DNA-free vaccines which are currently on trial (Ashley et al, 1987;Cappel et al, 1982;Mertz et al, 1984). These mixed protein vaccines will cause seroconversion of seronegatire volunteers but herpes simplex infections may still result with the possibility of ensuing recurrent infections (Ashley et al, 1987).…”

Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research

“…The bound fraction was further inactivated with formalin and compounded with alum. Most seronegative vaccinees developed neutralizing and antibody-dependent cell-mediated cytotoxicity antibodies and lymphoproliferative responses to HSV-2, but HSV-1-seropositive vaccinees had no increase in preexisting responses (177). The HSV-reactive T-cell clones recovered from vaccinated, initially HSV-seronegative donors were mostly CD4 ϩ and CD8 Ϫ ; a subset of these clones had CTL activity (299).…”