Genetically Engineered Attenuated Herpes Simplex Viruses

Abstract

Two recombinant herpes simplex viruses, of type 1 background, were constructed with two large deletions and duplicate sets (type 1 and type 2) of the genes coding for glycoproteins D, G, and E. One recombinant (R7020) is thymidine kinase-positive, and the other (R7017) is thymidine kinase-negative. Evaluation in rodents indicated that these viruses are genetically stable, capable of establishing latency, protective against severe herpetic diseases, and protective against the establishment of latency. In Aotus monkeys, R7020 replicates at the site of inoculation but does not disseminate in the body. It can reactivate from the latent state but without causing recurrent lesions, even in immunosuppressed monkeys.