Genetically engineered attenuated herpes simplex viruses

Area of Science:

• Virology
• Vaccinology
• Immunology

Background:

• Herpes simplex virus (HSV) infections are a global health concern.
• Current treatments are palliative, highlighting the need for effective vaccines.
• Recombinant viral vectors offer a promising strategy for vaccine development.

Purpose of the Study:

• To construct and evaluate novel recombinant herpes simplex viruses (HSVs) as potential vaccines.
• To assess the genetic stability, latency, and protective efficacy of these recombinants.
• To determine the safety and behavior of a lead candidate (R7020) in a non-human primate model.

Main Methods:

• Construction of two recombinant HSV-1 vectors (R7020 and R7017) with deletions and duplicated glycoprotein genes (gD, gG, gE).
• Evaluation of genetic stability, latency, and protection against HSV disease in rodent models.
• Assessment of R7020 replication, dissemination, reactivation, and lesion development in Aotus monkeys, including under immunosuppression.

Main Results:

• Both R7020 and R7017 demonstrated genetic stability and ability to establish latency in rodents.
• The recombinant viruses provided significant protection against severe herpetic disease and prevented latency establishment.
• In Aotus monkeys, R7020 replicated locally, did not disseminate, and reactivated without causing lesions, even when immunosuppressed.

Conclusions:

• Recombinant HSV vectors R7020 and R7017 are genetically stable and demonstrate potent protective efficacy against HSV disease and latency in preclinical models.
• R7020 exhibits a favorable safety profile in Aotus monkeys, with controlled replication and asymptomatic reactivation.
• These findings support the further development of these recombinant HSV vectors as potential vaccines against herpes simplex virus infections.