Epstein-Barr virus (EBV) infects at least 90% of the adult population worldwide and is the primary cause of infectious mononucleosis. Symptoms include sore throat, cervical lymphadenopathy, fatigue, upper respiratory tract congestion, headache, fever, and myalgia. In a clinical setting, diagnosis of infectious mononucleosis is typically based on the presence of these symptoms in addition to a detectable heterophile antibody response [1]. Because heterophile antibodies do not specifically recognize EBV antigens, they are not useful for the laboratory study of EBV-specific infection.

Enzyme immunoassays (EIAs) are routinely used to detect EBV-specific antibodies. The presence of IgM antibodies against the viral capsid antigen (VCA) is particularly useful for identifying primary EBV infection because these antibodies are usually found only during the first few months after the onset of symptoms. Conversion from a negative to a positive VCA IgG can also be used as a marker of acute infection, but this method is not preferred because VCA IgG persists for life and therefore cannot be used to distinguish between recent and past infection [1]. Another standard marker for studying the progression of EBV infection is the presence of IgG antibodies against EBV nuclear antigen 1 (EBNA-1). The combination of these three antibody responses can distinguish between acute and past EBV infection [2]. Immunoblotting, in which the antigen(s) of interest is coated on a solid phase, could also be useful for the characterization of antibody responses over time. The stage of infection can be distinguished by testing sera for the presence of different immediate early (IEA), early (EA), and late-developing antibodies [2]. The advantage of using immunoblotting rather than EIA is that several antigens can be interrogated at once, presenting a more comprehensive profile of an individual's antibody response.

Our prospective studies have identified 80 cases of laboratory-documented primary EBV infection among university undergraduates, with the maximum severity of illness (SOI) scores ranging from 0 (completely asymptomatic) to 6 (bedridden) [3], [4], [5]. Understanding host factors responsible for limiting the severity of primary EBV infection is crucial for evaluating prevention and treatment strategies. We recently found that higher titers of IgG antibody against EBV gp350 were associated with less severe infectious mononucleosis, whereas amounts of IgG class antibody against EBV VCA and EBNA-1 were not [4]. We decided to further explore the association of EBV-specific antibodies with SOI scores by investigating IgG antibody responses to 6 EBV proteins using a commercially available line immunoblot assay.