Protectivity of herpes simplex virus antigens: Studies in mice on the adjuvant effect of PICLC and on the dependence of protection on T cell competence

Abstract

The efficacy of a herpes simplex virus type 1 (HSV-1) envelope antigen (EAG) preparation against HSV infection was studied in T cell competent and T cell deficient mice. Immuno-competent mice were successfully protected against herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2) infection when immunized 2 weeks prior to this infection with a heat-inactivated whole virus preparation or a HSV-1 envelope antigen (HSV-1 EAG) preparation. Since HSV-1 EAG was considerably less effective than the whole virus preparation, a poly.riboinosinic-poly.ribocytidylic acid complex with poly-L-lysine and carboxymethylcellulose (PICLC) was used as adjuvant. Immunization with HSV-1 EAG plus PICLC resulted in a pronounced increase of this protection rate as compared with that obtained after immunization solely with HSV-1 EAG. PICLC alone, however, offered no protection when given 2 weeks before challenge. In T cell deficient nu/nu mice no protection was achieved with HSV-1 EAG while their T cell competent, heterozygous littermates were protected. From these results it may be concluded that T cell competence is a prerequisite for establishing a protective immunity against HSV infection after immunization with HSV-1 EAG.

Escherichia coli-derived envelope protein gD but not gC antigens of herpes simplex virus protect mice against a lethal challenge with HSV-1 and HSV-2

“…The enzyme-linked immunosorbent assay (ELISA) method used for measuring anti-HSV antibodies has been described by Moser et al (1981) and the measurement of neutralizing antibody titers by Hilfenhaus et al (1981).…”

“…As a positive control we used an HSV-1 envelope preparation (EAG), published in detail by Hilfenhaus et al (1981) As a negative control, mice were mock immunized with phosphate buffered saline (PBS), containing the pMF2-encoded cI::]3gal fusion protein (Amann et al 1984b) including the adjuvant to be tested. Each immunization dose is given in ~tg of total fusion protein.…”

“…The challenge experiments were done according to Hilfenhaus et al (1981). Hairless immuno-competent mice were obtained from Bomholtgard (Ry, Denmark).…”

“…Experiments were only evaluated when the survival rate in the control group (100 Ixg pMF2 encoded cI::13gal fusion protein per immunization; in PBS with adjuvant) did not exceed 3/10 or 4/15, respectively. HSV-1 strain Wal (Kirchner 1977) and HSV-2 strain ER (Dundarov and Falke 1972) were prepared as described by Hilfenhaus et al (1981).…”

“…A subunit vaccine consisting of HSV glycoproteins, which is free from viral DNA seems to be an appropiate form for a HSV vaccine. In recent years, several workers have obtained subunit preparations for possible use as vaccines from HSV virions using various detergents (Kitces et al 1977;Hilfenhaus et al 1981;Skinner et al 1978;Scriba 1982;Muklis et al 1986). …”