Performance characteristics of a quantitative, standardised varicella zoster IgG time resolved fluorescence immunoassay (VZV TRFIA) for measuring antibody following natural infection

Abstract

Infection by Varicella Zoster virus (VZV) during pregnancy has been associated with adverse foetal development and more severe disease in the mother. Accurate determination of VZV immunity in pregnant women exposed to VZV, with no history of chickenpox, guides therapeutic interventions. The accepted gold standard assay for the determination of immunity/protection against Varicella Zoster virus was for many years the fluorescent antibody to membrane antigen (FAMA) assay which is labour intensive and subjective. A validated alternative is the Merck glycoprotein EIA (Merck Sharp & Dohme Research Laboratories, West Point, PA, USA) which reports VZV IgG levels in enzyme units per ml (EU/ml) because an internal, non-international reference serum is used as calibrator. Comparison of different VZV IgG detection assays is hampered by a lack of an agreed cut-off in standardised units. A time resolved fluorescence immunoassay (TRFIA) for VZV IgG using British Standard VZV antibody has been developed and standardised. The limit of detection of VZV IgG by this assay was of the order 39–78 mIU/ml. Following comparison with the Merck glycoprotein EIA and the application of the USA Advisory Committee on Immunization Practices recommended 5.0 EU/ml cut-off the following standardised cut-offs in mIU/ml are proposed. A VZV TRFIA IgG cut-off of less than 100 mIU/ml VZV IgG equates with susceptibility and an equivocal range of 100 mIU/ml to less than 150 mIU/ml is proposed. VZV IgG levels of 150 mIU/ml, or greater, are indicative of natural infection at some time and the ability to mount a protective immune response is inferred.