ABVIC: an improved serological test to resolve indeterminate diagnoses for herpes simplex virus 2 (HSV-2)

Abstract

Abstract Approximately 50 million Americans are infected with herpes simplex virus type 2 (HSV-2) and may, at any time, transmit infectious virus to sexual partners. Current HSV-2 serological antibody tests are imperfect; 5–6% of those who initiate HSV-2 ELISA IgG screening receive low-positive results, known to include about 50% false-positives compared to HSV Western Blot, the current gold standard test. Even when low-positive samples are run by Western, ~20% obtain indeterminate results. We report a new, flow-cytometry-based method that measures serum antibody-binding to virus-infected cells (ABVIC). Unlike the glycoprotein G-based HerpeSelect assay, ABVIC tests for antibodies to ~30 HSV-2 antigens and appears to be ~100-fold more sensitive than the gG-2-based antibody capture ELISA. We report that when serum was collected from n=17 patients who had previously received “HSV-2 indeterminate” results by Western Blot, the ABVIC test offered a clear answer in every case. Sixteen of 17 were HSV-2 seronegative by ABVIC and only 1 of 17 was weakly HSV-2 seropositive. Most of the “Indeterminate” serum samples exhibited high background, which produces weak reactivity in the HerpeSelect and Western blot assays, but which does not confound the internally controlled ABVIC assay. We conclude that the highly quantitative, flow cytometry-based ABVIC test may be used to resolve the vast majority of “HSV-2 Indeterminate” results that have misled thousands of patients to the erroneous conclusion that they carry HSV-2 and pose a transmission risk to others.