Large scale comparison of adjuvant effects on immunogenicity and protection in a herpes simplex virus type 1 vaccination model.

Following primary infection with Herpes Simplex Virus (HSV), the virus persists in episomal form in the local sensory ganglia. Periodic reactivation by various stimuli results in a recrudescent lesion at or near the initial site of infection due to retrograde axonal transport [l]. As yet there is no suitable vaccine for its prevention within the human population p]. We investigated the potential of a large number of commercial and experimental adjuvant preparations to promote a protective immune response using an HSV-1 glycoprotein subunit vaccine. The various formulations induced markedly different degrees of protection and humoral immune responses, with no correlation between these parameters. We are currently assessing the cellular immune responses generated by the same group of adjuvants and will attempt to correlate these with protection. The results emphasise the requirement of adjuvants when using subunit preparations as vaccine formulations and demonstrate that the magnitude and effectiveness of the induced immune response varies greatly with the choice of adjuvant. Subunit antigen was prepared by propagation of HSV-1 (F strain) in Vero cells followed by subsequent detergent extraction as previously described 131. Adjuvant preparations used were MPL i TDM (Sigma, Poole, Dorset), Gerbu and Gerbu MZ (Gerbu Biotechnik GmbH, Germany), 8-Mercaptoguanosine (Sigma), Pofymethyl methacryla te (PMMA) (Aldrich), Neuraminidase Galactose oxidase (NAG01 NA (BDH, UK) and GO (Sigma), Hunters' TiterMaxTM (Sigma), SCOMS, Adjuvant peptide (Sigma), Dehydroisoandrosterone (Sigma), Interferony (Sigma), Vitamin D3 (Sigma), Monophosphoryl Lipid A (MPL, S. minnesota) (Sigma), Peptech GMDP (Peptech, UK; 10 R and 0.2 a dose), Stearyf tyrosine (BioChem Therapeutics Inc., Canada), Freund's complete and incomplete adjuvants (Sigma), Monranide ISA 51 (SEPPIC, France), Alum precipitated subunit vaccine, Liposomes Control vaccine prepararions non adjuvanted subunit vaccine and PBS alone. All animals received 5 pg total protein in conjunction with adjuvant at a recommended dose [4]. Formulations were administered subcutaneously as one 0.2ml injection to groups of 10 Balb/c mice on day 0. Post immunisation sera were taken on day 10. Mice were challenged idraperitoneally with 10 LD50 HSV-1 WAL strain (3 .26~104 pfu/0.2ml dose) on day 23 and post challenge bleeds were performed on day 30. Following the administration of 10 LD50 HSV-1 (WAL), mice were observed for subsequent death over a 21 day period. A broad range of protection levels, ranging from