Preparation and immunogenicity of vaccine Ac NFU1 (S-) MRC towards the prevention of herpes genitalis.

Abstract

SUMMARY A subunit antigenoid vaccine, Ac NFU, (S-) MRC, was used to prevent primary herpes genitalis in 60 subjects considered to be at risk of this infection. There was no evidence of serious local or general side effects.Neutralising antibody responses were detected in 59% and 90% of subjects receiving the low and high doses of vaccine respectively; immunoprecipitating antibody was detected at a lower frequency, namely in 23/o and 43% of subjects receiving the low and high doses respectively. After a mean follow-up period of 18 months none of the vaccinated subjects contracted herpes genitalis after completing the vaccination course.

Comparative studies of HSV‐1 antigens solubilised from infected cells by using non‐ionic or zwitterionic detergents

“…In addition, vaccinia virus recombinants or mouse cells expressing gB or gD have been reported to induce HSV-specific cytotoxic T lymphocytes (CTL's) and lymphoproliferation [Wachsman et al, 1987;Blacklaws et al, 1987;McLaughlin-Taylor et al, 19881, while monoclonal antibodies reactive with epitopes of gB, gC, or gD have passively protected mice against HSV infection [Kumel et al, 19851. These studies would suggest that to induce a fully and optimally effective response against HSV infections, a candidate vaccine should consist not of a single glycoprotein, no matter how that glycoprotein is presented to the immune system, but rather of several HSV glycoproteins and possibly other HSV proteins as well [Martin et al, 19881. Subunit HSV vaccines consisting of a number of HSV glycoproteins have been shown by several groups to be immunogenic in animals [Kutinova et al, 1980;Hilleman et al, 1981;Skinner et al, 1982;Meignier et al, 1987;Stanberry et a]., 1987; Jennings et al, 19881, and the present studies provide further characteristics of such a vaccine prepared by using a zwitterionic detergent [Mukhlis et al, 1986;Jennings et al, 19881. This zwittergent-solubilised vaccine is compared, for reactivity with monoclonal antibodies (Mabs) against HSV-1, radioimmunoprecipitation (RIP) with polyclonal HSV-1 antiserum and immunogenicity in mice, with a parallel preparation solubilised from HSV-1-infected cells by using the non-ionic detergent, Nonidet P40 (NP40).…”

Zwitterionic detergent solubilisation of HSV-1 surface antigens

“…We have found that Empigen extraction of HSV-1 infected Vero cells does result in the presence, in SDG (and SC) preparations of small amounts (<0.01 gg/100 ~tg protein) of DNA as determined by the method of Burton [4]; however this can be removed using deoxyribunuclease [21,28]. In earlier studies, other workers producing HSV antigen preparations for possible use as vaccines in man and employing NP40 or Triton-X-100 detergents [5,17,24,28,41], have for the most part, not reported which HSV glycoproteins are present in their preparations. The Empigen-extracted SDG preparations described in the present study have been shown to contain four HSV-1 gtycoproteins gB, gC, gD and gE, some of which have been found, as individual glycoproteins, to provide protections in animals against HSV challenge [11,20,25,37,39].…”

“…After incubation at 37 °C for 2448 h, when 90% of cells showed cytopathic effect, the supernatant fluid was discarded, the cells collected, washed twice with phosphate-buffered saline, pH 7.2 (PBS) and resuspended in 4 x their volume of PBS containing either 5% Triton-X-100 [17,38], 1% NP40 [41], or 2.5% Empigen, and left for 30rains in an ice-bath. After sonication for 30 secs using an MSE 150-watt ultrasonic disintegrator at full power, the cell-detergent mixtures were centrifuged at 100,000 g for 2 h. Following dialysis against PBS for 3 to 5 days, resulting crude Empigen-extracted HSV-1 antigen preparations contained < 0.001% of cationic active matter.…”

“…In the U.S.A., a glycoprotein-subunit HSV-2 vaccine prepared by detergent extraction using Triton-X-100 and purified by affinity chromatography, has been shown to induce both humoral and cellular responses in man to HSV-2 glycoproteins B, C, and D [2,28]. A DNAfree subunit HSV vaccine was found to induce antibodies and cell-mediated immunity (CMI) in a volunteer study in Belgium [6], while a vaccine preparation obtained using Nonidet P40 (NP40) elicited neutralising antibody responses in man in a study in the United Kingdom [41]. These results suggest that antigen preparations containing a mixture of purified HSV glycoproteins, will provide both humoral and cellular immunity in man, although their ability to protect against either primary or recurrent infections remains uncertain.…”

“…Amongst a number of different approaches [10,14,16,22], has been the conventional detergent extraction and subsequent purification of viral surface glycoproteins in an immunogenic form from purified whole virus particles [5,18] or from virus-infected cells [21,24,28,41]. In addition, a number of workers have purified individual glycoproteins from HSV strains and demonstrated that such preparations can provide protection in animals [7,11,20,25,37,38].…”