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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11722263PMC
http://dx.doi.org/10.1101/2024.11.20.624603DOI Listing

Publication Analysis

Top Keywords

vaccination replication-dead
8
prime-boost vaccination
8
mice
5
vaccination
4
replication-dead murine
4
murine gammaherpesvirus
4
gammaherpesvirus lacking
4
lacking viral
4
viral pathogenesis
4
pathogenesis genes
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!