title: A Longitudinal Hepatitis B Vaccine Cohort Demonstrates Long-lasting Hepatitis B Virus (HBV) Cellular Immunity Despite Loss of Antibody Against HBV Surface Antigen.
abstract: Long-lasting protection resulting from hepatitis B vaccine, despite loss of antibody against hepatitis B virus (HBV) surface antigen (anti-HBs), is undetermined.
  
  
  
  We recruited persons from a cohort vaccinated with plasma-derived hepatitis B vaccine in 1981 who have been followed periodically since. We performed serological testing for anti-HBs and microRNA-155 and assessed HBV-specific T-cell responses by enzyme-linked immunospot and cytometric bead array. Study subgroups were defined 32 years after vaccination as having an anti-HBs level of either ≥10 mIU/mL (group 1; n = 13) or <10 mIU/mL (group 2; n = 31).
  
  
  
  All 44 participants, regardless of anti-HBs level, tested positive for tumor necrosis factor α, interleukin 10, or interleukin 6 production by HBV surface antigen-specific T cells. The frequency of natural killer T cells correlated with the level of anti-HBs (P = .008). The proportion of participants who demonstrated T-cell responses to HBV core antigen varied among the cytokines measured, suggesting some natural exposure to HBV in the study group. No participant had evidence of breakthrough HBV infection.
  
  
  
  Evidence of long-lasting cellular immunity, regardless of anti-HBs level, suggests that protection afforded by primary immunization with plasma-derived hepatitis B vaccine during childhood and adulthood lasts at least 32 years.
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC) WWAMI School of Medical Education, College of Health, University of Alaska Anchorage.
authors.forename: Brenna C
authors.initials: BC
authors.lastname: Simons
authors.affiliation: Division of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, Georgia.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Spradling
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC).
authors.forename: Dana J T
authors.initials: DJ
authors.lastname: Bruden
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC).
authors.forename: Carolyn
authors.initials: C
authors.lastname: Zanis
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC).
authors.forename: Samantha
authors.initials: S
authors.lastname: Case
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium.
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Choromanski
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle.
authors.forename: Minjun
authors.initials: M
authors.lastname: Apodaca
authors.affiliation: WWAMI School of Medical Education, College of Health, University of Alaska Anchorage.
authors.forename: Hazel D
authors.initials: HD
authors.lastname: Brogdon
authors.affiliation: WWAMI School of Medical Education, College of Health, University of Alaska Anchorage.
authors.forename: Gaelen
authors.initials: G
authors.lastname: Dwyer
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium.
authors.forename: Mary
authors.initials: M
authors.lastname: Snowball
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium.
authors.forename: Susan
authors.initials: S
authors.lastname: Negus
authors.affiliation: Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC).
authors.forename: Michael G
authors.initials: MG
authors.lastname: Bruce
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.affiliation: WWAMI School of Medical Education, College of Health, University of Alaska Anchorage.
authors.forename: Cindy
authors.initials: C
authors.lastname: Knall
authors.affiliation: Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium Arctic Investigations Program, Division of Preparedness and Emerging Infections, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention (CDC).
authors.forename: Brian J
authors.initials: BJ
authors.lastname: McMahon
mesh_terms: D000328:Adult; D003584:Cytological Techniques; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008137:Longitudinal Studies; D008297:Male; D035683:MicroRNAs / Q000032:analysis; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: antibody against hepatitis B surface antigen; booster vaccination; cellular immunity; hepatitis B virus; plasma-derived vaccine; vaccine