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While Epstein-Barr virus (EBV) is the major cause of nasopharyngeal carcinoma (NPC), the value of the humoral immune response to EBV glycoproteins and NPC development remains unclear. Correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC requires systematic study. Here, we applied a cytometry-based method and enzyme-linked immunosorbent assay to measure neutralization of infectivity and antibody response to EBV glycoproteins (gH/gL, gB, gp350, and gp42) of plasma samples from 20 NPC cases and 20 high-risk and 20 low-risk healthy controls nested within a screening cohort in Sihui, southern China. We found that NPC cases have similar plasma neutralizing activity in both B cells and epithelial cells and EBV glycoprotein-specific IgA and IgG antibody levels compared with those of healthy controls. Significant correlations were observed between gH/gL IgG and gB IgG and the neutralizing ability against EBV infection of epithelial cells and B cells. These results indicate that a high level of glycoprotein antibodies may favor protection against primary EBV infection, instead of being low-risk biomarkers for NPC in long-term EBV-infected adults. In conclusion, this study provides novel insights into the humoral immune response to EBV infection and NPC development, providing valuable leads for future research that is important for prevention and treatment of EBV-related diseases. IMPORTANCE Epstein-Barr virus (EBV) is a human oncogenic gammaherpesvirus that infects over 90% of humans in the world and is causally associated with a spectrum of epithelial and B-cell malignancies such as nasopharyngeal carcinoma (NPC). A prophylactic vaccine against EBV is called for, but no approved vaccine is available yet. Therefore, EBV remains a major public health concern. To facilitate novel vaccines and therapeutics for NPC, it is of great importance to explore the impact of humoral immune response to EBV glycoproteins before the development of NPC. Therefore, in this study, we systematically assessed the correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC development. These results provide valuable information that will contribute to designing effective prevention and treatment strategies for EBV-related diseases such as NPC.

Association between Antibody Responses to Epstein-Barr Virus Glycoproteins, Neutralization of Infectivity, and the Risk of Nasopharyngeal Carcinoma