Vaccination with a Replication-Dead Murine Gammaherpesvirus Lacking Viral Pathogenesis Genes Inhibits WT Virus...

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Gammaherpesviruses cause lifelong infections and are linked to cancer.
• Current vaccines against Epstein-Barr virus and Kaposi sarcoma herpesvirus are lacking.
• Murine gammaherpesvirus-68 (MHV68) infection in mice serves as a model for studying gammaherpesvirus pathogenesis and vaccine development.

Purpose of the Study:

• To develop an improved replication-dead virus (RDV) vaccine for gammaherpesviruses.
• To assess the immunogenicity and protective efficacy of an RDV lacking specific genes (M1-M4 and TMERs 6, 7, 8).
• To evaluate the vaccine's potential for blocking viral replication, latency, and reactivation.

Main Methods:

• Generation of a modified RDV (RDV-50.stop∆M1-M4) lacking essential genes M1-M4 and TMERs 6, 7, 8.
• Prime-boost vaccination of mice with the modified RDV.
• Assessment of neutralizing antibody and CD8 T-cell responses.
• Challenge with wild-type MHV68 to evaluate protection against lytic replication, latency, and reactivation.

Main Results:

• Prime-boost vaccination with RDV-50.stop∆M1-M4 induced comparable neutralizing antibodies and virus-specific CD8 T-cell responses to the parental RDV-50.stop vaccine.
• Vaccinated mice showed a significant reduction in MHV68 lytic replication.
• Vaccination led to reduced viral latency and reactivation following challenge with wild-type MHV68.

Conclusions:

• The M1-M4 genes and TMERs 6, 7, and 8 are not essential for eliciting protective immunity against MHV68.
• The modified RDV vaccine candidate demonstrates potential for controlling gammaherpesvirus infections.
• This strategy advances the development of vaccines against oncogenic gammaherpesviruses like KSHV.