Healthcare & Immunology

Biography

Biography: Lbachir BenMohamed

Abstract

ABSTRACT

Herpes simplex virus type 1 (HSV-1) is a prevalent human pathogen that infects over 3.72 billion individuals worldwide and can cause potentially blinding recurrent corneal herpetic disease. HSV-1 establishes latency within sensory neurons of trigeminal ganglia (TG) and TG-resident CD8⁺ T cells play a critical role in preventing its reactivation. The repertoire, phenotype and function of protective CD8⁺ T cells are unknown. Bolstering the apparent feeble numbers of CD8⁺ T cells in TG remains a challenge for immunotherapeutic strategies. In this study, a comprehensive panel of 467 HLA-A*0201-restricted CD8⁺ T cell epitopes were predicted from the entire HSV-1 genome. CD8⁺ T cell responses to these genome-wide epitopes were compared in HSV-1 seropositive symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent herpetic disease) vs. asymptomatic (ASYMP) individuals (who are infected but never experienced any recurrent herpetic disease). Frequent polyfunctional HSV-specific effector memory IFN-g⁺CD107^a/b+CD44^highCD62L^lowCD8⁺ T_EM cells were detected in ASYMP individuals and were mainly directed against three “ASYMP” epitopes. In contrast, SYMP individuals have more mono-functional central memory CD44^highCD62L^highCD8⁺ T_CM cells. Furthermore, therapeutic immunization with an innovative prime/pull vaccine, based on priming with multiple “ASYMP” epitopes (prime) and neurotropic TG delivery of the T-cell attracting chemokine CXCL-10 (pull), boosted the number and function of CD44^highCD62L^lowCD8⁺ T_EM and tissue-resident CD103^highCD8⁺ T_RM cells in TG of latently infected HLA-A*0201 Tg mice and reduced recurrent ocular herpes following UV-B induced reactivation. These findings have profound implications in the development of T-cell-based immunotherapeutic strategies to treat blinding recurrent herpes infection and disease.