title: Immune exhaustion and immune senescence: two distinct pathways for HBV vaccine failure during HCV and/or HIV infection.
abstract: Given the shared risk factors for transmission, co-infection of hepatitis B virus (HBV) with hepatitis C virus (HCV) and/or human immunodeficiency virus (HIV) is quite common, and may lead to increases in morbidity and mortality. As such, HBV vaccine is recommended as the primary means to prevent HBV super-infection in HCV- and/or HIV-infected individuals. However, vaccine response (sero-conversion with a hepatitis B surface antibody titer >10 IU/L) in this setting is often blunted, with poor response rates to standard HBV vaccinations in virally infected individuals when compared with the healthy subjects. This phenomenon also occurs to other vaccines in adults, such as pneumococcal and influenza vaccines, in other immunocompromised hosts who are really at risk for opportunistic infections, such as individuals with hemodialysis, transplant, and malignancy. In this review, we summarize the underlying mechanisms involving vaccine failure in these conditions, focusing on immune exhaustion and immune senescence--two distinct signaling pathways regulating cell function and fate. We raise the possibility that blocking these negative signaling pathways might improve success rates of immunizations in the setting of chronic viral infection.
authors: Department of Veterans Affairs, Hepatitis (HCV/HBV/HIV) Program, James H. Quillen VA Medical Center, Johnson City, TN 37614, USA. yao@etsu.edu
authors: Zhi Q
authors: ZQ
authors: Yao
authors: Jonathan P
authors: JP
authors: Moorman
mesh_terms: D060085:Coinfection; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000401:mortality; D006510:Hepatitis B Antibodies / Q000097:blood; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology / Q000627:therapeutic use*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology* / Q000401:mortality; D006801:Humans; D016867:Immunocompromised Host; D012307:Risk Factors; D015163:Superinfection; D017211:Treatment Failure
chemical_list: D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines
references: J Immunol. 2012 Jul 15;189(2):755-66
references: 22706088
references: Immunogenetics. 1995;41(6):366-74
references: 7759133
references: J Immunol. 2001 Nov 1;167(9):4838-43
references: 11673487
references: PLoS One. 2010 Aug 18;5(8):e12273
references: 20806065
references: Nat Med. 2002 Aug;8(8):793-800
references: 12091876
references: Vaccine. 1996 Dec;14(17-18):1647-50
references: 9032894
references: Annu Rev Biochem. 2004;73:39-85
references: 15189136
references: Immunity. 2004 May;20(5):529-38
references: 15142522
references: Vaccine. 2011 Apr 12;29(17):3169-76
references: 21376795
references: Nature. 2006 Feb 9;439(7077):682-7
references: 16382236
references: J Clin Gastroenterol. 1992 Jan;14(1):27-30
references: 1532609
references: Immunology. 2011 Mar;132(3):421-31
references: 21091911
references: Biologicals. 2012 May;40(3):180-6
references: 22305086
references: J Viral Hepat. 2008 Jul;15(7):538-50
references: 18397223
references: Int Immunol. 2007 Jul;19(7):813-24
references: 17606980
references: Hepatology. 2000 Feb;31(2):521-7
references: 10655280
references: J Infect Dis. 1988 Sep;158(3):666-7
references: 3411157
references: APMIS. 2005 Jul-Aug;113(7-8):526-35
references: 16086823
references: HIV Med. 2007 Jul;8(5):295-9
references: 17561875
references: Vaccine. 2006 Jan 30;24(5):572-7
references: 16171909
references: Hepatology. 2005 Jun;41(6):1383-90
references: 15915462
references: Clin Infect Dis. 2008 Aug 15;47(4):542-53
references: 18627268
references: Lancet. 2002 Dec 14;360(9349):1921-6
references: 12493258
references: Genes Immun. 2001 Nov;2(7):367-72
references: 11704802
references: PLoS One. 2012;7(9):e44611
references: 22957088
references: Vaccine. 2000 Oct 15;19(4-5):437-41
references: 11027806
references: Clin Exp Med. 2007 Jun;7(2):65-71
references: 17609878
references: Viral Immunol. 2010 Oct;23(5):487-95
references: 20883163
references: J Hepatol. 1998 Jan;28(1):27-33
references: 9537860
references: Lancet Infect Dis. 2010 May;10(5):338-49
references: 20417416
references: Trends Immunol. 2001 May;22(5):265-8
references: 11323285
references: Viral Immunol. 2007 Summer;20(2):276-87
references: 17603844
references: J Infect Dis. 2005 May 1;191(9):1442-50
references: 15809902
references: Genes Dev. 2003 Mar 1;17(5):615-28
references: 12629044
references: Liver Transpl. 2007 Mar;13(3):434-42
references: 17318860
references: Vaccine. 2002 Nov 1;20(31-32):3644-9
references: 12399191
references: J Infect Dis. 1991 May;163(5):1138-40
references: 2019762
references: Bioessays. 2012 Dec;34(12):1050-9
references: 23012250
references: Science. 2003 Jun 6;300(5625):1542-8
references: 12791985
references: Nature. 2003 Jan 30;421(6922):499-506
references: 12556884
references: Clin Exp Immunol. 2005 Apr;140(1):126-37
references: 15762884
references: Arch Intern Med. 2006 Aug 14-28;166(15):1632-41
references: 16908797
references: Clin Infect Dis. 2003 Aug 1;37(3):438-47
references: 12884170
references: Virology. 2003 Sep 15;314(1):271-82
references: 14517080
references: J Clin Invest. 2010 Dec;120(12):4546-57
references: 21084749
references: Nat Rev Immunol. 2004 May;4(5):336-47
references: 15122199
references: Nat Rev Immunol. 2003 Jun;3(6):454-62
references: 12776205
references: J Infect Dis. 2003 Aug 15;188(4):571-7
references: 12898445
references: Clin Liver Dis. 2007 Nov;11(4):917-43, ix-x
references: 17981235
references: Virology. 2004 Aug 15;326(1):20-8
references: 15262491
references: Nat Rev Immunol. 2002 Feb;2(2):116-26
references: 11910893
references: Immunol Invest. 2011;40(3):243-64
references: 21291295
references: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5405-10
references: 10792035
references: J Virol. 2007 Apr;81(8):4215-25
references: 17287266
references: J Hepatol. 2002 Sep;37(3):387-92
references: 12175635
references: J Exp Med. 2003 Jul 7;198(1):39-50
references: 12847136
references: J Clin Invest. 2003 Mar;111(6):915-24
references: 12639998
references: J Infect Dis. 1989 Oct;160(4):577-82
references: 2571646
references: Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14733-8
references: 20679213
references: J Immunol. 2007 Aug 1;179(3):1979-87
references: 17641065
references: J Med Virol. 2010 May;82(6):929-33
references: 20419805
references: Immunol Cell Biol. 2011 May;89(4):535-9
references: 20975732
references: Lancet Infect Dis. 2002 Jul;2(7):395-403
references: 12127351
references: Tissue Antigens. 1998 Oct;52(4):374-80
references: 9820601
references: J Exp Med. 2008 Nov 24;205(12):2699-701
references: 19015312
references: Eur J Immunol. 2010 Sep;40(9):2493-505
references: 20623550
references: Immunology. 2009 Oct;128(2):227-35
references: 19740379
references: Clin Infect Dis. 2002 Dec 1;35(11):1368-75
references: 12439800
references: PLoS One. 2011;6(5):e19664
references: 21637332
references: Hepatology. 2004 Jan;39(1):51-7
references: 14752822
references: AIDS. 1992 Jun;6(6):571-4
references: 1388879
references: J Immunol. 1995 Jan 15;154(2):520-9
references: 7814865
references: Vaccine. 2003 Mar 7;21(11-12):1174-9
references: 12559795
references: Clin Infect Dis. 1994 Mar;18(3):339-47
references: 8011813
references: Vaccine. 2008 Nov 5;26(47):5967-72
references: 18804140
references: N Engl J Med. 2011 Jan 20;364(3):236-47
references: 21247314
references: Curr HIV Res. 2011 Jul;9(5):289-94
references: 21916840
references: Blood. 2005 Sep 1;106(5):1668-75
references: 15899915
references: Exp Gerontol. 2007 May;42(5):432-7
references: 17307327
references: N Engl J Med. 1987 Mar 5;316(10):630-1
references: 3807959
references: AIDS. 1997 Apr;11(5):597-606
references: 9108941
references: Dig Dis Sci. 2009 Sep;54(9):2016-25
references: 19517231
references: Ann N Y Acad Sci. 2012 Jan;1247:69-82
references: 22224726
references: J Med Virol. 2007 Nov;79(11):1679-85
references: 17854026
references: J Virol. 2007 Sep;81(17):9249-58
references: 17567698
references: Am J Med. 2005 Oct;118 Suppl 10A:21S-27S
references: 16271537
references: Immunology. 2008 Oct;125(2):197-207
references: 18397267
references: J Exp Med. 2008 Nov 24;205(12):2763-79
references: 19001139
references: Ann Intern Med. 1988 Jul 15;109(2):101-5
references: 2968064
references: Nat Rev Immunol. 2002 Jun;2(6):410-6
references: 12093007