Gammaherpesviruses are oncogenic pathogens that establish lifelong infections. There are no FDA-approved vaccines against Epstein-Barr virus or Kaposi sarcoma herpesvirus. Murine gammaherpesvirus-68 (MHV68) infection of mice provides a system for investigating of gammaherpesvirus pathogenesis and testing vaccine strategies. Prime-boost vaccination with a replication-dead virus (RDV) that does not express the essential replication and transactivator protein (RTA) encoded by RDV-50.stop) protected against WT virus replication and reduce latency in C57BL/6 mice and prevented lethal disease in mice. To further improve the RDV vaccine and more closely model KSHV vaccine design, we generated an RDV lacking the unique M1-M4 genes and the non-coding tRNA-miRNA-encoded RNAs (TMERs) 6, 7, and 8 that collectively promote latency of MHV68 . Prime-boost vaccination of mice with RDV-50.stopΔM1-M4 elicited neutralizing antibodies and virus-specific CD8 T-cell responses in lungs and spleens, the respective sites of acute replication and latency, that were comparable to RDV-50.stop vaccination. When challenged with WT MHV68, vaccinated mice exhibited a near-complete block of lytic replication and a reduction in latency and reactivation. We conclude that major determinants of MHV68 pathogenesis are not required components for eliciting a protective immune response.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722263 | PMC |
http://dx.doi.org/10.1101/2024.11.20.624603 | DOI Listing |
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