Comparison of different forms of herpes simplex replication-defective mutant viruses as vaccines in a mouse model of HSV-2 genital infection

Some subunit vaccines composed of herpes simplex virus (HSV) glycoproteins have been shown to protect guinea pigs against primary and recurrent genita l infection by HSV-2. However, these vaccines were ineffective or only marg inally effective in clinical trials. To attempt to define an animal model t hat would better discriminate the protective capacity of different vaccine formulations, we have examined the requirements for vaccine-induced protect ion against HSV-2 infection and disease in a mouse genital model. Unlike th e guinea pig model where inactivated viral vaccines can protect nearly as w ell as live viral vaccines, inactivated viral vaccine afforded little prote ction in this mouse model. Using replication-defective mutant viruses as a form of live viral vaccine, we found that the extent of protection conferre d by live vaccine was proportional to the amount of replication-defective m utant virus inoculated, over doses from 10(4) to 10(6) PFU. Furthermore, th e mouse genital model showed quantitative differences in the degree of prot ection induced by various viral vaccine constructs. An HSV-2 replication-de fective mutant virus protected better than an HSV-1 replication-defective m utant that expressed HSV-2 glycoprotein D, which in turn protected better t han an HSV-2 replication-defective mutant virus. We conclude that this mous e genital model can rank different vaccine constructs for their capacity to induce protective immunity. Thus, genital infection of the mouse with HSV- 2 may provide a stringent animal model that can predict the relative capaci ty of viral vaccines to stimulate protective immunity against HSV-2. (C) 20 01 Academic Press.