Development of three KSHV vaccine platforms and chimeric MHV68-K-G for in vivo mouse infection study

Abstract Kaposi's sarcoma-associated herpesvirus (KSHV) is a prevalent virus that establishes a lifelong persistent infection in humans and is associated with Kaposi's sarcoma (KS) and primary effusion lymphomas (PELs). Despite the reduction in complications associated with HIV infection due to combination antiretroviral therapy, KS still occurs in individuals with well-controlled HIV infection, in older men without HIV infection (classic KS), in sub-Saharan Africa (endemic KS), and in transplant recipients (iatrogenic KS). Despite being a pressing human health problem, very little research has been conducted to date on potential vaccine development against KSHV infection and its associated diseases. This is primarily due to the lack of significant interest as well as the absence of an effective animal model that supports in vivo studies on KSHV infection. For this reason, recombinant Murine Herpesvirus 68 (MHV68) has been used as the murine counterpart of KSHV in a small, manageable mouse model. The goal of this U01 application is twofold: firstly, to test three different novel vaccine platforms against KSHV infection, and secondly, to develop chimeric MHV68 carrying the replacement of KSHV glycoprotein (MHV68-K-G) as a surrogate challenge virus for testing the efficacy of KSHV vaccines in an in vivo mouse model.