A HSV1 mutant leads to an attenuated phenotype and induces immunity with a protective effect.

Author summary Herpes simplex virus type 1 (HSV1) may lead to various herpes infections and can establish latent infection in neurons, which shows a high infectivity rate in populations. There is currently no effective therapeutic and prophylactic vaccine against HSV1. Previous studies have indicated that attenuated or deficient HSV1 vaccines are capable of safely eliciting a comprehensive protective immune response. With the advances in genomic modification technologies and accumulated knowledge of viral-encoded proteins, various predictable vaccine candidates can be reliably designed. In this work, a mutant M6 containing mutations in theUL7,UL41,LAT,Us3,Us11andUs12genes was established. Furthermore, the proliferation characteristics, virulence phenotype and immunogenicity of the mutant were analyzed in different cells and in mice and rhesus macaques. Herpes simplex virus type 1 (HSV1) is a complicated structural agent with a sophisticated transcription process and a high infection rate. A vaccine against HSV1 is urgently needed. As multiple viral-encoded proteins, including structural and nonstructural proteins, contribute to immune response stimulation, an attenuated or deficient HSV1 vaccine may be relatively reliable. Advances in genomic modification technologies provide reliable means of constructing various HSV vaccine candidates. Based on our previous work, an M6 mutant with mutations in theUL7,UL41,LAT,Us3,Us11andUs12genes was established. The mutant exhibited low proliferation in cells and an attenuated phenotype in an animal model. Furthermore, in mice and rhesus monkeys, the mutant can induce remarkable serum neutralizing antibody titers and T cell activation and protect against HSV1 challenge by impeding viral replication, dissemination and pathogenesis.