Development and Utilization of West Nile Virus Antibody Assays in a Reference Laboratory Setting

Following the introduction of West Nile virus (WNV) into the United States in 1999, our facility responded quickly to develop assays for WNV immunoglobulin M (IgM) and IgG. The first-generation WNV IgM and IgG enzyme-linked immunosorbent assays (ELISAs) were developed in house and were utilized for three seasons (2000 to 2002) as sensitive and specific tools for detecting WNV infections. Second-generation versions of these assays were introduced in kit format beginning in 2003 and have been used effectively since that time by many laboratories, including our own facility. With the recognition that WNV IgM persists in some infected individuals, we and others have sought to identify alternative assays that clearly distinguish recent from past WNV infection. Our studies showed that one potential marker, WNV IgA, was no better than WNV IgM as an indicator of recent infection. In studies of WNV IgG avidity, we found that detection of low-avidity IgG was an excellent marker of recent infection, but for reasons that remain unclear, some WNV-infected persons produce high-avidity IgG very soon after infection. We continue to explore opportunities to characterize the antibody response to WNV, with the goal of identifying markers that improve our ability to diagnose WNV infection and to distinguish recent from past exposure.