Differences in the Epstein-Barr Virus gp350 IgA Antibody Response Are Associated With Increased Risk for Coinfection With a Second Strain of Epstein-Barr Virus

Abstract

Background. The Epstein-Barr virus (EBV) viral glycoprotein gp350 has been proposed as a candidate antigen for an EBV vaccine. However, the proposed formulations of these vaccines have not taken into account the presence of 2 unique EBV strains (EBV-1 and EBV-2) present in areas of high incidence of the EBV-associated cancer, Burkitt lymphoma. Methods. In this study, we analyze the kinetics of EBV-1 and EBV-2 infection in an asymptomatic infant cohort from Kisumu, Kenya. We also analyzed the kinetics of the antibody response against 5 EBV antigens, gp350 (IgG and IgA), VCA (IgG), EBNA-1 (IgG), EAd (IgG), and Zta (IgG). Results. We observed a high frequency of coinfection with both EBV types over time, with the only observable defect in the antibody response in infants coinfected being a significantly lower level of anti-gp350 IgA at peak response. Gp350 IgA levels were also significantly lower in coinfected infants 2.5 months postinfection and at the time of coinfection. Conclusions. These results suggest that anti-gp350 IgA antibodies may be important for sterilizing immunity against secondary infection. These findings have implications for the development of an efficacious EBV vaccine to prevent both EBV-1 and EBV-2 infection in a population at high risk for Burkitt lymphoma.

Mutual detection of Kaposi's sarcoma‐associated herpesvirus and Epstein–Barr virus in blood and saliva of Cameroonians with and without Kaposi's sarcoma

“…Serum IgG against synthetic peptides covering immunodominant epitopes of the viral capsid antigen P18 (VCA), EBV nuclear antigen 1 (EBNA1), diffuse early antigen complex (EAd) and against the EBV‐encoded recombinant glycoprotein 350/220 (gp350) were measured using a multiplexed bead‐based assay as previously described, at a 1/200 serum dilution. Background‐subtracted median fluorescent intensity levels (MFI) were log10 transformed for subsequent analyses.…”

Epstein-Barr Virus and Systemic Autoimmune Diseases

“…Among the 85 proteins encoded in the EBV genome, several have been used for detection of Abs to EBV including EBNA1, EBNA2, VCAp23, VCAp18, early antigen diffuse (EAD), gP350, BARF1 (Table 1) (15,(94)(95)(96)(97). IM has previously been associated with the presence of so-called heterophile Abs, however, this test has a rather low specificity and it remains unclear, what the test actually measures (2,98).…”

“…While type 1 (B95-8, GD1, and Akata) is the main EBV type prevalent worldwide, type 2 (AG876 and P3HR-1) is as abundant as type 1 in sub-Saharan Africa (13). The EBV variants have different replicative properties and individuals may become superinfected with two or more strains (14)(15)(16).…”

A reliable Epstein-Barr Virus classification based on phylogenomic and population analyses

“…The geographical distribution of EBV types shows that type 1 is the most prevalent in the world, predominantly in Europe, Asia and North and South America. Instead, type 2 is more frequent in Alaska, Papua New Guinea and Central Africa 17 , with far higher frequency in countries like Kenya 18 . In fact, dual infections with these EBV types have also been reported in these locations 18,19 , including intertypic recombinants with type 1 EBNA2 and type 2 EBNA3s 20–22 .…”