Epstein-Barr virus (EBV) is a ubiquitous, worldwide infectious agent that causes
infectious mononucleosis, affecting >90% of the world's population. Currently,
enzyme-linked
immunosorbent assay, mostly with purified preparations of EBV
cell extracts to capture
immunoglobulin M (
IgM)
antibodies in patients' serum, is used for primary diagnosis. Our objective was to determine whether a small set of
peptides could contain sufficient immunogenic information to replace solid-phase
antigens in EBV diagnostics. Using
monoclonal antibodies, we selected four
peptides that mimic different
epitopes of EBV from a phage-displayed
random peptide library. To assess their diagnostic value, we screened a panel of 62 individual EBV
IgM sera for their reactivities with the
peptides alone. For all
peptides, there was a clear distinction between the EBV-positive and the EBV-negative samples, resulting in 100% specificity. The sensitivities were 88%, 85%, 71%, and 54% for
peptides F1, A3, gp125, and A2, respectively. Any combination of
peptides increased the sensitivity, indicating that individual
peptides react with different subsets of
antibodies. Furthermore, when the F1 and the gp125
peptides were coupled to
bovine serum albumin and screened against 216 serum samples, there were dramatic improvements in sensitivities (95% and 92%, respectively) and little cross-reactivity with the other
peptides encountered during acute
viral infections, including
rheumatoid factor. This study shows the potential for the use of
peptide mimotopes as alternatives to the complex
antigens used in current serodiagnostics for
EBV infection.