Apr 14, 2020

Deletion of immune evasion genes provides an effective vaccine design for tumor-associated herpesviruses

BioRxiv : the Preprint Server for Biology
G. BrarTing-Ting Wu

Abstract

Vaccines based on live attenuated viruses often induce broad, multifaceted immune responses. However, they also usually sacrifice immunogenicity for attenuation. It is particularly difficult to elicit an effective vaccine for herpesviruses due to an armament of immune evasion genes and a latent phase. Here, to overcome the limitation of attenuation, we developed a rational herpesvirus vaccine in which viral immune evasion genes were deleted to enhance immunogenicity while also attaining safety. To test this vaccine strategy, we utilized murine gammaherpesvirus-68 (MHV-68) as a proof-of-concept model for the cancer-associated human {gamma}-herpesviruses, Epstein-Barr virus and Kaposi sarcoma-associated herpesvirus. We engineered a recombinant MHV-68 virus by targeted inactivation of viral antagonists of type I interferon (IFN-I) pathway and deletion of the latency locus responsible for persistent infection. This recombinant virus is highly attenuated with no measurable capacity for replication, latency, or persistence in immunocompetent hosts. It stimulates robust innate immunity, differentiates virus-specific memory T cells, and elicits neutralizing antibodies. A single vaccination affords durable protection that blocks the est...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Diabetes Mellitus, Non-Insulin-Dependent
Dysequilibrium Syndrome
Differential Diagnosis
Familial Primary Pulmonary Hypertension
Structure
Pierre Robin Syndrome
Simulation
Analysis
Lasso-O Measuring Tape

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