An R2 non-neuroinvasive herpes simplex virus type 2 vaccine

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PROJECT SUMMARY There is an unmet need for a herpes simplex virus (HSV) vaccine. We propose to develop a live-attenuated HSV-2 vaccine based on our R2 technology platform. R2 vaccines show unprecedented safety and efficacy in animal models, and offer antigenicity superior to subunit/mRNA and single-round vaccine designs. R2 vaccines are also the first live-attenuated alphaherpesvirus vaccines that lack neuroinvasive potential, and thereby are incapable of establishing life-long infections in the nervous system. In phase I of this fast-track STTR application, we propose to: (i) produce a HSV- 2 self-excising infectious clone of a low-passage clinical isolate, (ii) use the clone to produce a HSV-2 R2 recombinant, and (iii) characterize the R2 vaccine in culture side by side with our existing HSV-1 R2 vaccine candidate. In phase II, the HSV-2 R2 vaccine will be tested for safety, immunogenicity, and efficacy in mice and guinea pigs. This work will provide the foundation to advance product development to clinical trials.