Preinfection Prophylaxis with Herpes Simplex Virus Glycoprotein Immunogens: Factors Influencing Efficacy

Abstract

SUMMARYUsing a guinea-pig model of genital herpes simplex virus (HSV) infection we explored the protection afforded by preinfection immunization with HSV glycoproteins. Glycoprotein immunogens prepared by recombinant DNA technology were found to be as effective as immunogens purified from HSV-infected cell cultures. Immunized animals developed less severe primary disease and also experienced less frequent recurrent infections. Protection was influenced by both adjuvant and route of administration. These studies suggest that recombinant HSV glycoproteins may be effective immunogens for human clinical trials, but that the development of an effective vaccine will require identification of new potent adjuvants that are safe for human use.

Mice Genetic Immunization with Plasmid DNA Encoding a Secreted Form of HSV-1 gB Induces a Protective Immune Response against Herpes simplex Virus Type 1 Infection

“…Nevertheless, a vaccine against HSV is still awaited. Most vaccine strategies for HSV have focused on the development of subunit vaccines consisting of one or more HSV glycoproteins [1][2][3][4][5][6]. However, to date, clinical trials with glycoprotein D (gD) seem to indicate that these vaccines may be less than ideal for either prevention or therapy against HSV infection in humans [7].…”

Immunization with DNA vaccines encoding glycoprotein D or glycoprotein B, alone or in combination, induces protective immunity in animal models of herpes simplex virus-2 disease.

“…It has been shown with protein subunit vaccines (5,6) and recently with high-dose DNA immunization (24) that significant reduction in primary genital disease also resulted in reduced latent infection and decreased recurrence. The extent of protection against primary disease found in the study presented here suggests that prophylactic immunization with a low-dose combination of gD and AgB-2 DNA would be effective against recurrence; experiments to evaluate this are ongoing.…”

“…Having established that low doses of DNA were effective in the mouse model, we then tested the prophylactic effect of a low-dosage combination of these DNAs in the guinea pig vaginal-infection model. Genital disease in guinea pigs closely resembles that in humans (38,39), and the model has been widely used to test potential vaccines (5,6) (36,37). Escherichia coli DH5a (GIBCO/ BRL) was transformed according to the manufacturer's specifications.…”

Expression of the herpes simplex virus type 1 glycoprotein E in human cells and in Escherichia coli: protection studies against lethal viral infection in mice

“…Mice vaccinated with hgE-ls developed high serum titres of HSV-l-neutralizing antibodies and were significantly protected from intraperitoneal lethal HSV-1 challenge, whereas mice vaccinated with bgE-lt exhibited only moderate levels of protective immunity. These results demonstrate that the expression ofgE-1 in human cells has a strong impact on its protective efficacy and that most importantly the hgE-1 s protein could be of value as a component of an HSV multi-subunit vaccine.Herpes simplex virus (HSV) glycoproteins appear to be promising candidates for subunit vaccine development against HSV infection (Burke, 1993;Stanberry et al, 1989). Of the eleven known glycoproteins, gD, gB and gC were the first antigens to be expressed in various expression systems and to be shown to provide encouraging results in animal models of HSV disease (Laurence et al…”

“…Herpes simplex virus (HSV) glycoproteins appear to be promising candidates for subunit vaccine development against HSV infection (Burke, 1993;Stanberry et al, 1989). Of the eleven known glycoproteins, gD, gB and gC were the first antigens to be expressed in various expression systems and to be shown to provide encouraging results in animal models of HSV disease (Laurence et al, 1984;Pachl et al, 1987;Krishna et al, 1989;Weir et al, 1989;Kino, 1990;Manservigi et al, 1990;Burke, 1991 ;Ghiasi etal., 1991Ghiasi etal., , 1992a.…”