Limits in reliability of glycoprotein G-based type-specific serologic assays for herpes simplex virus types 1 and 2

Type-specific serologic assays for herpes simplex virus (HSV) types 1 and 2 based on glycoprotein G-1 (gG-1) (HSV-1) and gG-2 (HSV-2) discriminate bet ween antibodies against HSV-1 and HSV-2, We previously developed a Western blot assay using gG-1 and gG-2 expressed in baculovirus, performed extensiv e validation studies, and determined that it was both sensitive and specifi c for type-specific detection of HSV antibody. Here we report that, among a cohort of Thai military recruits, the serostatus of some individuals chang ed from positive to negative over time (6.6% among those ever positive for HSV-1, and 14.9% among those ever positive fur NSV-2). We tested a subset o f these specimens in three other gG-based assays: an enzyme-linked immunoso rbent assay, an immunoblot strip assay, and a Western blot assay. positive- to-negative shifts occurred in every assay; the frequency of the shifts ran ged from 6.1% to 21.2% of the specimen sets tested. There was only limited agreement among the assays concerning which individuals lost reactivity, Th is inaccuracy, exhibited by all of the assay protocols, was not predicted b y validation studies employing specimens from cross-sectional studies and w as most pronounced in HSV-2 testing. This argues for the inclusion of seria l blood specimens in serologic assay validation procedures.