Rapid antibody responses to Epstein-Barr virus correlate with reduced severity of primary infection

Background: We investigated Epstein-Barr virus (EBV) antibody kinetics in university freshmen who developed laboratory-documented primary EBV infection during prospective studies and correlated these kinetics with disease severity. Methods: EBV-naïve participants had blood collected periodically and sera tested for EBV-specific antibodies with line blot and enzyme immunoassays. The line blot assay contained EBNA-1, p18, p23, BZLF-1, p138, and p54 antigens; the enzyme immunoassay contained viral capsid antigen and EBNA-1. Severity of illness (SOI) was graded 0 (asymptomatic) to 6 (bedridden). Participants with maximum SOI scores 0–2 were compared with those whose maximum SOI scores were 3–6. Time to first antibody response was analyzed using the semi-parametric COX model. Results: A total of 201 sera from 38 college students collected before, during, and after primary EBV infection were tested. Earlier antibody responses correlated with milder symptoms. This was most pronounced for late-developing antibodies. The median time to development of p18 IgG was significantly earlier among low-SOI participants (64 days) than high-SOI patients (119 days; P = 0.0003).). Participants with mild disease developed EBNA-1 antibodies sooner than participants with more severe disease (125 days versus >270 days; P = 0.017). Participants with mild disease also showed more rapid loss of antibodies against IgG EA p138 and p54 ≥12 weeks post-infection (P = 0.012 and P = 0.026, respectively). Conclusions: These data suggest that rapid antibody responses to EBV correlate with reduced severity of primary EBV infection.