CD4+ T Cells Are Not Required for Suppression of Hepatitis B Virus Replication in the Liver of Vaccinated Chimpanzees.
Humans vaccinated with hepatitis B virus (HBV) surface antigen (HBsAg) sometimes develop humoral and cellular immunity to HBV proteins such as core and polymerase that are not vaccine components, providing indirect evidence that vaccine-induced immunity is not sterilizing. We previously described CD4(+) T-cell immunity against HBsAg and polymerase in chimpanzees after vaccination and HBV challenge. Here, vaccinated chimpanzees with protective levels of anti-HBsAg antibodies were rechallenged with HBV after antibody-mediated CD4(+) T-cell depletion. HBV DNA was detected in liver for at least 3 months after rechallenge, but virus replication was suppressed, as revealed by the absence of HBV DNA and HBsAg in serum. These observations provide direct virological evidence for nonsterilizing immunity in individuals with anti-HBsAg antibodies and are consistent with translation of HBV proteins to prime immune responses. They also indicate that CD4(+) T cells were not required for suppression of HBV replication in previously vaccinated individuals.
Department of Pathology, Medical University of Warsaw, Poland Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Jolanta
J
Rybczynska
Center for Vaccines and Immunity, Nationwide Children's Hospital.
Katherine
K
Campbell
Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Saleem
S
Kamili
Victorian Infectious Disease Reference Laboratory, North Melbourne, Australia.
Stephen
S
Locarnini
Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia.
Krzysztof
K
Krawczynski
Center for Vaccines and Immunity, Nationwide Children's Hospital Department of Pediatrics, College of Medicine, The Ohio State University, Columbus.
Christopher M
CM
Walker
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015684:Gene Products, pol / Q000235:genetics / Q000276:immunology; D006509:Hepatitis B / Q000276:immunology* / Q000517:prevention & control; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000821:virology*; D002679:Pan troglodytes; D014779:Virus Replication / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D015684:Gene Products, pol; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C066027:P protein, Hepatitis B virus
CD4+ T cell; class II epitope; hepatitis B virus; persistence; sterilizing immunity; vaccine