title: High Levels of Antibody that Neutralize B-cell Infection of Epstein-Barr Virus and that Bind EBV gp350 Are Associated with a Lower Risk of Nasopharyngeal Carcinoma.
abstract: Elevated IgA antibodies indicative of ongoing exposure to Epstein-Barr virus (EBV) are high-risk biomarkers for nasopharyngeal carcinoma (NPC), an EBV-related epithelial tumor. However, protective biomarkers that limit exposure to the virus have not been defined. We evaluated whether antibodies that can neutralize EBV infection by targeting glycoproteins involved in viral cell entry, including EBV vaccine candidate glycoprotein 350 (gp350), were associated with lower NPC risk.
  
  
  
  In a prospective cohort of 2,557 individuals from 358 high-risk NPC multiplex families in Taiwan, we identified 21 incident NPC cases and 50 disease-free controls. To complement data from high-risk families, we further identified 30 prevalent NPC cases and 50 healthy controls from the general Taiwanese population. We quantified EBV-neutralizing antibody, antibodies against EBV glycoproteins involved in B-cell and epithelial cell entry, and anti-EBNA1 IgA, a high-risk NPC biomarker.
  
  
  
  EBV-neutralizing antibodies blocking B-cell infection and anti-gp350 antibodies were present at significantly higher levels in disease-free controls compared with incident NPC cases (P < 0.03). Family members with both low EBV-neutralizing potential and elevated EBNA1 IgA had a 7-fold increased risk of NPC (95% CI, 1.9-28.7). Neutralizing antibodies against epithelial cell infection did not differ between incident cases and disease-free controls. Anti-glycoprotein antibody levels measured at diagnosis (prevalent NPC) were significantly higher than levels measured prior to diagnosis (P < 0.01).
  
  
  
  Elevated titers of EBV-neutralizing antibody and anti-gp350 antibody were low-risk biomarkers for NPC. These data suggest that a vaccine that induces potent EBV gp350 and B-cell-neutralizing antibodies could reduce the risk of EBV-related cancers such as NPC. Clin Cancer Res; 22(14); 3451-7. ©2016 AACR.
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland. anna.coghill@nih.gov.
authors.forename: Anna E
authors.initials: AE
authors.lastname: Coghill
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Wei
authors.initials: W
authors.lastname: Bu
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Hanh
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Wan-Lun
authors.initials: WL
authors.lastname: Hsu
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland. Division of Cancer Prevention, NCI, Bethesda, Maryland.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Lou
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, Bethesda, Maryland.
authors.forename: Allan
authors.initials: A
authors.lastname: Hildesheim
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Cohen
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology*; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D002277:Carcinoma / Q000097:blood / Q000276:immunology* / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000097:blood / Q000276:immunology* / Q000821:virology; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015415:Biomarkers; D019309:Epstein-Barr Virus Nuclear Antigens; D006023:Glycoproteins; D007070:Immunoglobulin A; C417029:EBV-encoded nuclear antigen 1