Anti-VZV monoclonal antibody, clone TG5

Varicella zoster virus (VZV) is a lymphotropic alpha-herpesvirinae subfamily member that produces varicella on primary infection and causes zoster, vascular disease and vision loss upon reactivation from latency. VZV-infected peripheral blood mononuclear cells (PBMCs) disseminate virus to distal organs to produce clinical disease. To assess immune evasion strategies elicited by VZV that may contribute to dissemination of infection, human PBMCs and VZV-specific CD8(+) T cells (V-CD8(+)) were mock- or VZV-infected and analyzed for immunoinhibitory protein PD-1, PD-L1, PD-L2, CTLA-4, LAG-3 and TIM-3 expression using flow cytometry. All VZV-infected PBMCs (monocytes, NK, NKT, B cells, CD4(+) and CD8(+) T cells) and V-CD8(+) showed significant elevations in PD-L1 expression compared to uninfected cells. VZV induced PD-L2 expression in B cells and V-CD8(+). Only VZV-infected CD8(+) T cells, NKT cells and V-CD8+ upregulated PD-1 expression, the immunoinhibitory receptor for PD-L1/PD-L2. VZV induced CTLA-4 expression only in V-CD8(+) and no significant changes in LAG-3 or TIM-3 expression were observed in V-CD8(+) or PBMC T cells. To test whether PD-L1, PD-L2 or CTLA-4 regulates V-CD8(+) effector function, autologous PBMCs were VZV-infected and co-cultured with V-CD8(+) cells in the presence of blocking antibodies against PD-L1, PD-L2 or CTLA-4; ELISAs revealed significant elevations in IFN only upon blocking of PD-L1. Together, these results identified additional immune cells that are permissive to VZV infection (monocytes, B cells and NKT cells); along with a novel mechanism for inhibiting CD8(+) T cell effector function through induction of PD-L1 expression. Author summary The burden of disease produced by VZV is significant, since 90% of the world population harbors latent virus. At least 50% of infected individuals will reactivate by 85 years of age to develop zoster, which is an established risk factor for stroke and myocardial infarction, as well as multisystem diseases with or without rash. VZV-infected PBMCs disseminate virus to distal organs to produce clinical disease. PD-L1 is an immunoinhibitory protein that interacts with PD-1, its receptor, expressed mainly on T cells to prevent their activation and subsequent clearance of virus- or malignantly transformed cells. We show here that all peripheral blood mononuclear cells have a dramatic induction of PD-L1 expression upon infection with VZV, which is combined with the induction of PD-1 expression on CD8(+) T cells, NKT cells and VZV-specific CD8(+) T cells. Blocking PD-L1 during co-culturing of VZV-specific CD8(+) T cells with autologous VZV-infected PBMCs enhanced IFN levels almost 2-fold compared to isotype controls. These results indicate that blocking PD-L1 expression during varicella or zoster may restore CD8(+) T cell effector function, enabling effective clearance of virus-infected cells to reduce viral spread and multisystem disease.

Background: Health care workers (HCWs) and students are at increased risk for blood borne infections and vaccine preventable diseases (VPDs). The aim of this study was to determine the seroprevalence of antibodies against measles, rubella, mumps, varicella zoster virus (VZV), hepatitis A and B viruses among HCWs and students and to determine whether there are differences according to gender and age group. Methods: Information about characteristics of the 1053 participants, history of disease and vaccination status were collected using a structured questionnaire. Serum samples were tested for antibodies by commercial immunoenzymatic assays. Results: Seropositivity rates were 57.1% for measles, 74% for mumps, 96.3% for rubella, 93.7% for VZV, 33.9% for hepatitis A virus and 92.2% for hepatitis B virus. Susceptibility rates among participants 18-26, 27-38 and >38 years of age were statistically significant for measles (46%, 18.6% and 0%; p < 0.001) and mumps (27.1%, 12.9% and 21.4%; p < 0.05), respectively. Conclusion: Low seropositivity rates for measles, mumps and HAV are important findings. For other diseases other than VZV, it is thought that vaccination without pre-screening is more appropriate. Healthcare institutions should have policies for screening and vaccination of their staff and students. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences.