CD154 expression is associated with neutralizing antibody titer levels postinfluenza vaccination in stem cell transplant patients and healthy adults.
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.
Seidel
Aprille
A
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.
Smith
David
D
Yung
Edward
E
Aquino
Lia
L
Srivastava
Tumul
T
Pullarkat
Vinod
V
Spielberger
Ricardo
R
Forman
Stephen J
SJ
Diamond
Don J
DJ
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
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D007371:Interferon-gamma
Vaccine. 2009 Apr 21;27(18):2469-74
19368788
Rev Infect Dis. 1983 Jul-Aug;5(4):723-36
6353529
J Med Virol. 2000 May;61(1):85-93
10745238
J Virol. 2007 Aug;81(16):8468-76
17553885
Vaccine. 2009 Jan 7;27(2):319-27
18977404
Bone Marrow Transplant. 2005 Apr;35(8):793-801
15750607
PLoS One. 2008 Aug 20;3(8):e2975
18714352
Bone Marrow Transplant. 1993 Oct;12(4):387-98
8275039
BMC Infect Dis. 2010 Mar 17;10:71
20236548
Eur Respir J. 2001 Dec;18(6):971-6
11829104
J Immunol. 2004 Mar 1;172(5):3305-18
14978139
Transplantation. 2008 Jul 27;86(2):257-63
18645488
J Exp Med. 2004 Dec 20;200(12):1613-22
15611289
J Immunol. 2004 Jul 1;173(1):673-81
15210831
Bone Marrow Transplant. 2005 Nov;36(10):897-900
16170332
J Virol. 2008 Mar;82(5):2565-9
18094159
Biol Blood Marrow Transplant. 2004 Jul;10(7):433-47
15205665
MMWR Recomm Rep. 2000 Oct;49(RR-10):1-125, CE1-7
11718124
Cancer Immunol Immunother. 2009 Dec;58(12):1949-57
19444444
N Engl J Med. 2009 Sep 24;361(13):1260-7
19776407
Vaccine. 2006 Jul 7;24(27-28):5546-51
16720062
Lancet. 2005 Feb 26-Mar 4;365(9461):773-80
15733718
Bone Marrow Transplant. 2008 Nov;42(10):637-41
18724396
Blood. 1996 Sep 1;88(5):1733-40
8781429
PLoS One. 2008 Jul 02;3(7):e2574
18596908
Immunol Rev. 2006 Jun;211:8-22
16824113
Bone Marrow Transplant. 2001 Oct;28(8):775-81
11781630
J Virol. 1991 Nov;65(11):6071-6
1920626
Br J Haematol. 2004 Nov;127(3):322-5
15491293
Blood. 1999 Dec 15;94(12):4029-35
10590046
Biol Blood Marrow Transplant. 2002;8(5):281-9
12064366
Clin Drug Investig. 1998;15(1):1-12
18370460
Nat Med. 2005 Oct;11(10):1113-7
16186817
Bone Marrow Transplant. 2008 Oct;42(7):483-7
18695668
Bone Marrow Transplant. 2005 Sep;36(5):411-5
15980884
Liver Transpl. 2001 Apr;7(4):311-3
11303290
Clin Infect Dis. 2005 Jul 15;41(2):273-4
15983934
Immunol Rev. 1997 Jun;157:73-8
9255623
J Immunol. 2005 Nov 1;175(9):5827-38
16237075
Vaccine. 2008 Aug 5;26(33):4210-7
18597900
J Immunol. 2006 Sep 1;177(5):2888-98
16920924
Bone Marrow Transplant. 1993 Jan;11(1):1-5
8431706
J Exp Med. 2007 Feb 19;204(2):299-309
17261633
Blood. 1994 Jul 15;84(2):657-63
8025290