Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital
infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no
vaccines available against
herpes simplex viral infections. However, a number of promising
vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated
viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV
vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV
infection indicating that a similar
vaccine approach may be feasible for HSVs. In this review, we summarize pre-clinical approaches to HSV
vaccine development and current efforts to test certain
vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1
vaccine strain to protect against both HSV-1 and HSV-2
infections.