Therapeutic immunization with EBNA-1 elicits responses to novel T cell epitopes in latently Lymphocryptovirus infected rhesus macaques (P4323)

Abstract

Abstract Epstein-Barr virus (EBV) is a gamma-Herpesvirus associated with lymphoma or nasopharyngeal carcinoma in immunocompromised patients. Lymphocryptovirus (LCV) infection of rhesus macaques replicates several characteristics of the human EBV infection. EBNA-1 is a nuclear virus protein expressed in all phases of EBV/LCV infections, essential for survival, malignant transformation, tumor progression and escape from host immune response. In spite of its importance for viral replication and survival, EBNA-1 is poorly immunogenic during lytic or latent infection. However, since protection against select experimental infections was achieved after enhancement of antigen immunogenicity through immunization, we hypothesized that eliciting EBNA-1-specific responses during chronic latent infection could increase control of EBV/LCV in vivo. We therefore attempted to enhance and broaden LCV EBNA-1 responses via immunization with an AdC68-LCV-EBNA-1 vector in groups of rhesus macaques that were latently infected with LCV but exhibiting low baseline responses. Following immunization, several CD4+ and CD8+ T cell epitopes were identified through IFN-g ELISPOT assays either as novel or markedly expanded responses. One such novel expanded CD8+ T cell epitope was mapped to a 9-mer peptide restricted by Mamu B*029, and a tetramer was developed for staining of specific CD8+ T cells. The study provides proof of concept that EBNA-1 may be a suitable vaccine target.