Evaluation of a prototype biplex VIDAS immunoassay for type-specific detection of HSV-1 and HSV-2 IgG antibodies

Type-specific serologic detection of IgG antibodies to herpes simplex virus (HSV)-1 and HSV-2 provides important diagnostic and epidemiological information. Novel assays are under development and require rigorous evaluation before routine clinical implementation. We compared the VIDAS HSV 1&2 IgG prototype assay (bioMérieux) with the widely used LIAISON HSV-1 and HSV-2 IgG assays (DiaSorin). Western blot (WB) analysis was used as the reference method to resolve discrepant results. A total of 501 serum samples from 348 patients were analyzed, including 259 patients with PCR-confirmed HSV-1 or HSV-2 infection. WB was performed on the 89 discordant samples between the two assays. For HSV-1 IgG detection, the VIDAS prototype assay showed a sensitivity of 95.4% and a specificity of 98.6%, compared with 98.9% and 94.9%, respectively, for the LIAISON HSV-1 IgG assay. For HSV-2 IgG, the VIDAS assay demonstrated a sensitivity of 100% but a lower specificity of 90.7%, whereas the LIAISON HSV-2 IgG assay showed a lower sensitivity of 88.2% and a higher specificity of 99.4%. Approximately 30% of the samples with high HSV-1 IgG index values yielded false-positive HSV-2 IgG results with the VIDAS assay. The receiver operating characteristic curve analysis indicated that increasing the VIDAS HSV-2 positivity threshold from 0.063 to 0.137 improved specificity to 98.9% while maintaining a sensitivity of 95.4%. For HSV-1 IgG detection, the VIDAS prototype assay showed performance comparable to that of the LIAISON assay. For HSV-2 IgG, optimization of the positivity threshold may substantially improve specificity, an important consideration in low-prevalence populations.

IMPORTANCE

Type-specific serology is an important complement to molecular diagnosis of herpes simplex virus (HSV) infections, helping distinguish primary, recurrent, and non-primary infections; assess neonatal transmission risk; and support patient counseling. Because western blot, the reference method, is not routinely available, the clinical value of HSV serology relies on the performance of automated immunoassays. We evaluated a novel VIDAS HSV 1&2 IgG biplex prototype assay and compared it with a widely used commercial assay. The VIDAS assay showed performance comparable to the LIAISON assay for HSV-1 IgG detection while offering simultaneous detection of HSV-1 and HSV-2 antibodies in a single test. For HSV-2 IgG, however, false-positive results were observed, particularly in samples with high HSV-1 antibody levels. Importantly, optimizing the HSV-2 positivity threshold improved specificity while maintaining high sensitivity. These findings provide data for assay optimization before commercialization and highlight the need to balance sensitivity and specificity for accurate clinical interpretation.