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Differences in the Epstein-Barr virus gp350 IgA antibody response are associated with increased risk for co-infection with a second strain of EBV

Smith, NA;Baresel, PC;Jackson, CL;Ogolla, S;Toko, EN;Heit, S;Piriou, E;Sumba, OP;Middeldorp, JM;Colborn, KL;Rochford, R;

The 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 two unique EBV strains (EBV-1 and EBV-2) present in areas of high incidence of the EBV associated cancer, Burkitt’s lymphoma. 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 five EBV antigens, gp350 (IgG and IgA), VCA (IgG), EBNA-1 (IgG), EAd (IgG), and Zta (IgG). We observed a high frequency of co-infection with both EBV types over time, with the only observable defect in the antibody response in infants co-infected being a significantly lower level of anti-gp350 IgA at peak response. Gp350 IgA levels were also significantly lower in co-infected infants 2.5 months post-infection and at the time of co-infection. 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’s lymphoma.