Vaccination with Recombinant Herpes Simplex Virus Glycoproteins: Protection Against Initial and Recurrent Genital Herpes

Abstract

The natural history of initial and subsequent recurrent herpes simplex virus (HSV) genital infection was studied in guinea pigs immunized with HSV glycoprotein vaccines before vaginal challenge with HSV-2. The vaccines used included HSV-1 glycoprotein B and HSV-1 glycoprotein D, both prepared by recombinant DNA techniques, and mixtures of HSV-1 or HSV-2 glycoproteins, prepared from infected cell monolayers by lectin chromatography. Immunizing guinea pigs with subunit HSV glycoprotein vaccines favorably altered the clinical and virological course of initial infection and substantially reduced the incidence, frequency, and duration of recurrent herpetic infections. The extent of protection was influenced by the nature of the glycoprotein vaccine, the immunizing dose, and the co-administration of adjuvant.

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

“…The HSV immunogen preparations were similar to those employed in our previous vaccine studies (Pachl et al, 1987;Stanberry et al, 1987;Myers et al, 1988;Sanchez-Pescador et al, 1988). An HSV-2 glycoprotein mixture (gP2) was prepared by detergent lysis of strain 333-infected Veto cells, followed by chromatography of the soluble fraction on lentil lectin-Sepharose (Pachl et al, 1987). As determined by radioimmunoprecipitation followed by SDS-PAGE or ELISA, this mixture contained approximately 15 ~ gB, 5 ~o gD, detectable amounts of glycoproteins gE and gG and many unidentified HSV and Vero cell proteins.…”

“…In initial studies we reported that immunization with a mixture of HSV glycoproteins provided protection against both primary and spontaneous recurrent disease when administered to guinea-pigs prior to intravaginal HSV-2 inoculation (Stanberry et al, 1987). Using this animal model we also showed that the administration of these glycoproteins, after the establishment of a latent infection, reduced both the frequency and severity of recurrent disease, as well as the frequency of cervicovaginal viral shedding (Myers et al, 1988;Stanberry et al, 1988).…”

“…Neither protein is produced as a fusion protein. These proteins were purified from the conditioned medium as described previously for gB (Pachl et al, 1987) and gD (Sanchez-Pescador et al, 1988), and were judged to be > 90~ homogeneous by SDS-PAGE. As a control for the recombinant antigen, dhfr-CHO cells were grown to confluence, lysed with detergent and the soluble extract (control extract) was passed over a lentil lectin-Sepharose column using the same protocol as used for the gP2 preparation.…”

“…Antibody to HSV was measured by ELISA using the gP2 mixture as a coating antigen as described previously (Stanberry et al, 1987(Stanberry et al, , 1988.…”

The Application of a Plasmid DNA Encoding IFN-α1 Postinfection Enhances Cumulative Survival of Herpes Simplex Virus Type 2 Vaginally Infected Mice

“…Vaccines using recombinant HSV-2 glycoproteins including glycoprotein (g)B and gD have been found to provide adequate protection against subsequent vaginal infection with HSV-2 in a guinea pig model (25) but clinical outcomes have not been forthcoming. Using an attenuated virus, another group found promising results measuring survival and clinical scores whether the virus was inoculated s.c. or intranasally (26).…”