Anti-Varicella Zoster Virus chimeric monoclonal antibody, clone E40C4E2

PURPOSE. While VZV DNA and antigen have been detected in acute and chronic VZV keratitis, it is unclear whether productive infection of corneal cells is ongoing or whether residual, noninfectious VZV antigens elicit inflammation. Herein, we examined VZV-infected primary human corneal epithelial cells (HCECs) and keratocytes (HKs) to elucidate the pathogenesis of VZV keratitis. METHODS. HCECs and HKs were mock-or VZV infected. Seven days later, cells were examined for morphology, proinflammatory cytokine and matrix metalloproteinase (MMP) release, ability to recruit peripheral blood mononuclear cells (PBMCs) and neutrophils, and MMP substrate cleavage. RESULTS. Both cell types synthesized infectious virus. VZV-infected HCECs proliferated, whereas VZV-infected HKs died. Compared to mock-infected cells, VZV-infected HCECs secreted significantly more IL-6, IL-8, IL-10, and IL-12p70 that were confirmed at the transcript level, and MMP-1 and MMP-9; conditioned supernatant attracted PBMCs and neutrophils and cleaved MMP substrates. In contrast, VZV-infected HKs suppressed cytokine secretion except for IL-8, which attracted neutrophils, and suppressed MMP release and substrate cleavage. CONCLUSIONS. Overall, VZV-infected HCECs recapitulate findings of VZV keratitis with respect to epithelial cell proliferation, pseudodendrite formation and creation of a proinflammatory environment, providing an in vitro model for VZV infection of corneal epithelial cells. Furthermore, the proliferation and persistence of VZV-infected HCECs suggest that these cells may serve as viral reservoirs if immune clearance is incomplete. Finally, the finding that VZV-infected HKs die and suppress most proinflammatory cytokines and MMPs may explain the widespread death of these cells with unchecked viral spread due to ineffective recruitment of PBMCs.

Introduction: Antibody tests for detecting varicella-zoster virus include the fluorescent-antibody-to-membrane-antigen (FAMA) assay, immune adherence hemagglutination assay (IAHA), enzyme immunoassay (EIA), and the glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). Although FAMA and gpELISA are highly sensitive, FAMA is not available commercially. Therefore, this study was performed to compare potential high-sensitivity tests with commercially available tests. Methods: Four antibody tests, FAMA, gpELISA, EIA, and IAHA, were performed using sera collected from 32 children aged 7 months-10 years. Using FAMA as a reference, the sensitivity and specificity of gpELISA, EIA, and IAHA were assessed. Subsequently, using gpELISA as a reference, the positive agreement rate of EIA and IAHA was assessed. Results: On a reference scale with FAMA set at 100%, the sensitivity and specificity of the antibody tests were as follows: gpELISA, 67% and 100%; EIA, 67% and 100%; and IAHA, 47% and 100%, respectively. The positive agreement rates of EIA and IAHA relative to gpELISA were 86% and 64%, respectively. Conclusions: gpELISA had a lower positive rate than did FAMA, and showed comparable sensitivity to that of EIA. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.