A Threshold in Anti–EBNA-1 Antibody Titers Distinguishes Salivary EBV Shedders From Nonshedders

Low anti-Epstein-Barr virus nuclear antigen (EBNA)-1 antibody titers are associated with reduced risk of Epstein-Barr virus (EBV)-related diseases. We hypothesized that individuals with exceptionally low anti-EBNA-1 levels represent a biologically distinct subgroup. Twenty healthy adults were classified by their antibody titers into 17 individuals with typical-range titers and 3 low outliers. Participants provided 204 saliva samples longitudinally. Typical-range participants frequently shed EBV, while low outliers had no detectable shedding (P = .0002). While all participants were confirmed to be EBV positive, nonshedders showed restricted antibody diversity limited to latent and immediate-early antigens. Our findings define a distinct nonshedder phenotype that suppresses viral replication despite harboring latent virus.