Kinetics of Epstein-Barr Virus (EBV) Neutralizing and Virus-Specific Antibodies after Primary Infection with EBV

Abstract

Prospective studies of antibodies to multiple Epstein-Barr virus (EBV) proteins and EBV neutralizing antibodies in the same individuals before, during, and after primary EBV infection have not been reported. We studied antibody responses to EBV in college students who acquired primary EBV infection during prospective surveillance and correlated the kinetics of antibody response with the severity of disease. Neutralizing antibodies and enzyme-linked immunosorbent assay (ELISA) antibodies to gp350, the major target of neutralizing antibody, reached peak levels at medians of 179 and 333 days after the onset of symptoms of infectious mononucleosis, respectively. No clear correlation was found between the severity of the symptoms of infectious mononucleosis and the peak levels of antibody to individual viral proteins or to neutralizing antibody. In summary, we found that titers of neutralizing antibody and antibodies to multiple EBV proteins increase over many months after primary infection with EBV.

High Epstein-Barr Virus Load and Genomic Diversity Are Associated with Generation of gp350-Specific Neutralizing Antibodies following Acute Infectious Mononucleosis

“…gp350-binding antibodies were detected in the majority of individuals with AIM at symptom onset (Fig. 1A) and increased in titer from AIM through CONV, with the levels during CONV being similar to those in healthy, agematched EBV-seropositive donors; these findings are compatible with those of recently reported studies (20,29).…”

“…The lack of detectable EBV-specific neutralizing activity in Raji cell assays from samples collected during AIM is consistent with previously reported data from studies using either a similar assay (20) or a B-cell transformation assay (29). However, using a more sensitive PCR-based assay with primary B cells, we detected neutralizing antibody activity in the plasma of the majority (83%) of AIM patients.…”

“…The EBV enhanced green fluorescent protein (eGFP)-tagged Raji cell neutralization assay performs comparably to a previously used transformation assay (19,20). Using this assay, IgG neutralizing activity was not detected in any AIM patients (Fig.…”

“…A flow cytometry-based assay was used to measure the neutralization of infection of Raji cells with the eGFP-tagged Akata isolate (Akata-eGFP); this method has been adopted as a suitable substitute for the traditional primary B-cell transformation assay (19,20,48). Briefly, plasma IgG (10 l of a 1-mg/ml stock) was mixed with a known titer of virus and incubated for 1 h at 37°C.…”

Lethal Hemorrhagic Disease and Clinical Illness Associated with Elephant Endotheliotropic Herpesvirus 1 Are Caused by Primary Infection: Implications for the Detection of Diagnostic Proteins

“…Antibody responses were assessed with the luciferase immunoprecipitation system (LIPS) assay (10). This assay has been used successfully in studies of human herpesviruses and other pathogens (11)(12)(13)(14)(15)(16) and does not require species-specific detection reagents, making it an excellent candidate for assessing Asian elephant antibody responses.…”