title: CD154 expression is associated with neutralizing antibody titer levels postinfluenza vaccination in stem cell transplant patients and healthy adults.
abstract: We undertook a prospective longitudinal study to examine humoral and cellular immune responses to influenza vaccination in hematopoietic cell transplant (HCT) patients and healthy adults. Healthy volunteers and HCT patients had blood samples taken prior to influenza vaccination and 30, 90, and 180 days postvaccination. Serum from pre- and postvaccination time points were tested for influenza A IgG and IgM by ELISA as well as tested for neutralizing antibody (NAb) titers via hemagglutination inhibition assay. Polychromatic flow cytometry was used to examine CD4(+) T cells for levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and CD154 (CD40 ligand) expression after stimulation with inactivated flu virus. In healthy subjects, we found a significant increase in Influenza A IgG and IgM levels as well as an increase in NAb titers pre- and post-influenza vaccination. Notably, NAb titers of most HCT patients did not rise to a protective level postvaccination. CD4(+) T cell expression of CD154 and cytokine responses were significantly reduced in HCT recipients compared to healthy adults. A lack of B cell reconstitution and dysfunctional CD4 T cell costimulation (as marked by low CD154 expression) is associated with low NAb levels postvaccination in HCT patients.
authors.affiliation: Division of Translational Vaccine Research, Department of Virology, Beckman Research Institute of the City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA 91010, USA.
authors.forename: Aprille
authors.initials: A
authors.lastname: Seidel
authors.forename: David
authors.initials: D
authors.lastname: Smith
authors.forename: Edward
authors.initials: E
authors.lastname: Yung
authors.forename: Lia
authors.initials: L
authors.lastname: Aquino
authors.forename: Tumul
authors.initials: T
authors.lastname: Srivastava
authors.forename: Vinod
authors.initials: V
authors.lastname: Pullarkat
authors.forename: Ricardo
authors.initials: R
authors.lastname: Spielberger
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Forman
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood* / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007251:Influenza, Human / Q000097:blood* / Q000276:immunology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma
references.citation: Vaccine. 2009 Apr 21;27(18):2469-74
references.pmid: 19368788
references.citation: Rev Infect Dis. 1983 Jul-Aug;5(4):723-36
references.pmid: 6353529
references.citation: J Med Virol. 2000 May;61(1):85-93
references.pmid: 10745238
references.citation: J Virol. 2007 Aug;81(16):8468-76
references.pmid: 17553885
references.citation: Vaccine. 2009 Jan 7;27(2):319-27
references.pmid: 18977404
references.citation: Bone Marrow Transplant. 2005 Apr;35(8):793-801
references.pmid: 15750607
references.citation: PLoS One. 2008 Aug 20;3(8):e2975
references.pmid: 18714352
references.citation: Bone Marrow Transplant. 1993 Oct;12(4):387-98
references.pmid: 8275039
references.citation: BMC Infect Dis. 2010 Mar 17;10:71
references.pmid: 20236548
references.citation: Eur Respir J. 2001 Dec;18(6):971-6
references.pmid: 11829104
references.citation: J Immunol. 2004 Mar 1;172(5):3305-18
references.pmid: 14978139
references.citation: Transplantation. 2008 Jul 27;86(2):257-63
references.pmid: 18645488
references.citation: J Exp Med. 2004 Dec 20;200(12):1613-22
references.pmid: 15611289
references.citation: J Immunol. 2004 Jul 1;173(1):673-81
references.pmid: 15210831
references.citation: Bone Marrow Transplant. 2005 Nov;36(10):897-900
references.pmid: 16170332
references.citation: J Virol. 2008 Mar;82(5):2565-9
references.pmid: 18094159
references.citation: Biol Blood Marrow Transplant. 2004 Jul;10(7):433-47
references.pmid: 15205665
references.citation: MMWR Recomm Rep. 2000 Oct;49(RR-10):1-125, CE1-7
references.pmid: 11718124
references.citation: Cancer Immunol Immunother. 2009 Dec;58(12):1949-57
references.pmid: 19444444
references.citation: N Engl J Med. 2009 Sep 24;361(13):1260-7
references.pmid: 19776407
references.citation: Vaccine. 2006 Jul 7;24(27-28):5546-51
references.pmid: 16720062
references.citation: Lancet. 2005 Feb 26-Mar 4;365(9461):773-80
references.pmid: 15733718
references.citation: Bone Marrow Transplant. 2008 Nov;42(10):637-41
references.pmid: 18724396
references.citation: Blood. 1996 Sep 1;88(5):1733-40
references.pmid: 8781429
references.citation: PLoS One. 2008 Jul 02;3(7):e2574
references.pmid: 18596908
references.citation: Immunol Rev. 2006 Jun;211:8-22
references.pmid: 16824113
references.citation: Bone Marrow Transplant. 2001 Oct;28(8):775-81
references.pmid: 11781630
references.citation: J Virol. 1991 Nov;65(11):6071-6
references.pmid: 1920626
references.citation: Br J Haematol. 2004 Nov;127(3):322-5
references.pmid: 15491293
references.citation: Blood. 1999 Dec 15;94(12):4029-35
references.pmid: 10590046
references.citation: Biol Blood Marrow Transplant. 2002;8(5):281-9
references.pmid: 12064366
references.citation: Clin Drug Investig. 1998;15(1):1-12
references.pmid: 18370460
references.citation: Nat Med. 2005 Oct;11(10):1113-7
references.pmid: 16186817
references.citation: Bone Marrow Transplant. 2008 Oct;42(7):483-7
references.pmid: 18695668
references.citation: Bone Marrow Transplant. 2005 Sep;36(5):411-5
references.pmid: 15980884
references.citation: Liver Transpl. 2001 Apr;7(4):311-3
references.pmid: 11303290
references.citation: Clin Infect Dis. 2005 Jul 15;41(2):273-4
references.pmid: 15983934
references.citation: Immunol Rev. 1997 Jun;157:73-8
references.pmid: 9255623
references.citation: J Immunol. 2005 Nov 1;175(9):5827-38
references.pmid: 16237075
references.citation: Vaccine. 2008 Aug 5;26(33):4210-7
references.pmid: 18597900
references.citation: J Immunol. 2006 Sep 1;177(5):2888-98
references.pmid: 16920924
references.citation: Bone Marrow Transplant. 1993 Jan;11(1):1-5
references.pmid: 8431706
references.citation: J Exp Med. 2007 Feb 19;204(2):299-309
references.pmid: 17261633
references.citation: Blood. 1994 Jul 15;84(2):657-63
references.pmid: 8025290