Immune Control and Vaccination against the Epstein-Barr Virus in Humanized Mice

Mice with reconstituted human immune system components (humanized mice) offer the unique opportunity to test vaccines preclinically in the context of vaccine adjuvant sensing by human antigen presenting cells and priming of human cytotoxic lymphocyte populations. These features are particularly attractive for immune control of the Epstein-Barr virus (EBV), which represents the most potent growth-transforming pathogen in man and exclusively relies on cytotoxic lymphocytes for its asymptomatic persistence in the vast majority of healthy virus carriers. This immune control is particularly impressive because EBV infects more than 95% of the human adult population and persists without pathology for more than 50 years in most of them. This review will discuss the pathologies that EBV elicits in humanized mice, which immune responses control it in this model, as well as which passive and active vaccination schemes with adoptive T cell transfer and with virus-like particles or individual antigens, respectively, have been explored in this model so far. EBV-specific CD8⁺ T cell priming in humanized mice could provide crucial insights into how cytotoxic lymphocytes against other viruses and tumors might be elicited by vaccination in humans.