Vaccination with an HSV-1 virus containing CD-137L reduces herpetic corneal disease when used both prophylactically and therapeutically.

Corneal infections with herpes simplex type 1 (HSV-1) are a leading cause of blindness in the world. At present the standard of care for corneal disease (herpetic stromal keratitis, HSK) is anti-virals and topical steroids. With the development of anti-viral resistant strains of the virus, it is important to discover new therapies for this disease. We have focused on the development of vaccines that would select for an immune response that controls both virus and corneal disease. As present most vaccines that have been studied tend to be efficacious when used in a prophylactic regimen. However, these vaccines are not effective when treating latently infected individuals when their disease is reactivated resulting in recurrent HSK. We decided to test the concept that if we were to include the co-stimulatory molecule CD137L in our vaccine construct that this would lead to success when used in a therapeutic paradigm. We present data indicating that this vaccine construct is effective in ameliorating both primary and recurrent forms of HSK. At this time, we cannot attribute this observation to specific mechanisms that may be mediating its protective effect, but that is something we wish to address in the future.