Replication-dead gammaherpesvirus vaccine protects against acute replication, reactivation from latency, and lethal challenge in mice.

Gammaherpesviruses establish chronic infections that place a host at life-long risk for the development of lymphoproliferative disorders. While these viruses are endemic within the adult human population, there are currently no FDA-approved vaccines available to prevent acute infection or the later onset of lymphoproliferative disorders. We report here the use of a prime-boost vaccination strategy utilizing replication-dead virus strains to protect mice from acute disease following challenge with WT virus. We demonstrate that vaccination with replication-dead viruses is both safe and effective within immunocompetent and immunodeficient mice, and protects from viral replication, reactivation, and onset of severe disease.