Merck Ad5/HIV induces broad innate immune activation that predicts CD8+ T-cell responses but is attenuated by preexisting Ad5 immunity

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 50, 2012, Pages E3503-E3512

  Zak, Daniel E ^a   Andersen Nissen, Erica ^b   Peterson, Eric R ^b   Sato, Alicia ^b   Hamilton, M Kristina ^a   Borgerding, Joleen ^b   Krishnamurty, Akshay T ^b   Chang, Joanne T ^b   Adams, Devin J ^b   Hensley, Tiffany R ^b   Salter, Alexander I ^b   Morgan, Cecilia A ^b,c   Duerr, Ann C ^b,c   De Rosa, Stephen C ^b,c,d   Aderem, Alan ^a,d   McElrath, M Juliana ^b,c,d  

^a SEATTLE BIOMEDICAL RESEARCH INSTITUTE   (United States)

^b Vaccine and Infectious Disease Institute   (United States)

^c Fred Hutchinson Cancer Research Center   (United States)

^d UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Immunogenicity; Immunology; Innate immunity; Systems biology; Systems vaccinology

Indexed keywords

ADENOVIRUS VECTOR; APOLIPOPROTEIN B MESSENGER RNA EDITING ENZYME CATALYTIC POLYPEPTIDE 3F; APOLIPOPROTEIN B MESSENGER RNA EDITING ENZYME CATALYTIC POLYPEPTIDE 3G; CD74 ANTIGEN; CD8 ANTIGEN; CHEMOKINE RECEPTOR CCR5; COMPLEMENT COMPONENT C1QB; CXCL11 CHEMOKINE; G PROTEIN COUPLED RECEPTOR; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GUANOSINE TRIPHOSPHATASE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; INTERFERON; INTERFERON REGULATORY FACTOR 1; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 10; INTERLEUKIN 28A; KILLER CELL IMMUNOGLOBULIN LIKE RECEPTOR 2DL1; KRUPPEL LIKE FACTOR 4; MONOCYTE CHEMOTACTIC PROTEIN 1; MONOCYTE CHEMOTACTIC PROTEIN 2; NEUTRALIZING ANTIBODY; NLRC5 PROTEIN; PLATELET DERIVED GROWTH FACTOR AA; RANTES; RIPK1 PROTEIN; STAT1 PROTEIN; TOLL LIKE RECEPTOR 3; TRANSCRIPTOME; UNCLASSIFIED DRUG; YELLOW FEVER VACCINE; AUTACOID; CHEMOKINE; CYTOKINE; LIVE VACCINE; VIRUS ANTIBODY;

ADULT; ARTICLE; BLOOD ANALYSIS; BONE MARROW CELL; CD8+ T LYMPHOCYTE; CELL ACTIVATION; CELL MIGRATION; CONTROLLED STUDY; CYTOKINE RESPONSE; FEMALE; GENE EXPRESSION; GENE IDENTIFICATION; GENETIC ASSOCIATION; HUMAN; HUMAN ADENOVIRUS 5; HUMAN CELL; HUMAN EXPERIMENT; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOCOMPETENT CELL; IMMUNOPROPHYLAXIS; INFLAMMATION; INNATE IMMUNITY; LYMPHOCYTE; MALE; META ANALYSIS (TOPIC); MONONUCLEAR CELL; MULTICENTER STUDY; NORMAL HUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; SIGNAL TRANSDUCTION; SYSTEM ANALYSIS; VACCINATION; BLOOD; GENE VECTOR; GENETICS; HUMAN ADENOVIRUS; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; MIDDLE AGED; PHYSIOLOGY; SYSTEMS BIOLOGY; VIRUS REPLICATION;

ADENOVIRUSES, HUMAN; ADULT; AIDS VACCINES; ANTIBODIES, NEUTRALIZING; ANTIBODIES, VIRAL; CD8-POSITIVE T-LYMPHOCYTES; CHEMOKINES; CYTOKINES; FEMALE; GENETIC VECTORS; HIV INFECTIONS; HUMANS; IMMUNITY, INNATE; INFLAMMATION MEDIATORS; LYMPHOCYTE ACTIVATION; MALE; MIDDLE AGED; SYSTEMS BIOLOGY; VACCINES, ATTENUATED; VIRUS REPLICATION; YELLOW FEVER VACCINE; YOUNG ADULT;

EID: 84874433635     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1208972109     Document Type: Article

References (68)

1. Rerks-Ngarm S, et al.; MOPH-TAVEG Investigators (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361(23):2209–2220.
2. Pulendran B, Ahmed R (2011) Immunological mechanisms of vaccination. Nat Immunol 12(6):509–517.
3. McElrath MJ, et al.; Step Study Protocol Team (2008) HIV-1 vaccine-induced immunity in the test-of-concept Step Study: A case-cohort analysis. Lancet 372(9653):1894–1905.
4. Buchbinder SP, et al.; Step Study Protocol Team (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): A double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372(9653):1881–1893.
5. Gray GE, et al.; HVTN 503/Phambili study team (2011) Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: A double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis 11 (7):507–515.
6. Rolland M, et al. (2011) Genetic impact of vaccination on breakthrough HIV-1 sequences from the STEP trial. Nat Med 17(3):366–371.
7. Hutnick NA, et al. (2009) Baseline Ad5 serostatus does not predict Ad5 HIV vaccine-induced expansion of adenovirus-specific CD4+ T cells. Nat Med 15(8):876–878.
8. O’Brien KL, et al. (2009) Adenovirus-specific immunity after immunization with an Ad5 HIV-1 vaccine candidate in humans. Nat Med 15(8):873–875.
9. Qureshi H, et al. (2012) Low-dose penile SIVmac251 exposure of rhesus macaques infected with adenovirus type 5 (Ad5) and then immunized with a replication-defective Ad5-based SIV gag/pol/nef vaccine recapitulates the results of the phase IIb step trial of a similar HIV-1 vaccine. J Virol 86(4):2239–2250.
10. Sullivan NJ, et al. (2011) CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nat Med 17(9):1128–1131.
11. Mu J, et al. (2009) Immunization with a bivalent adenovirus-vectored tuberculosis vaccine provides markedly improved protection over its monovalent counterpart against pulmonary tuberculosis. Mol Ther 17(6):1093–1100.
12. Andersen-Nissen E, Heit A, McElrath MJ (2012) Profiling immunity to HIV vaccines with systems biology. Curr Opin HIV AIDS 7(1):32–37.
13. Zak DE, Aderem A (2012) Overcoming limitations in the systems vaccinology approach: A pathway for accelerated HIV vaccine development. Curr Opin HIV AIDS 7 (1):58–63.
14. Gilchrist M, et al. (2006) Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441(7090):173–178.
15. Ramsey SA, et al. (2008) Uncovering a macrophage transcriptional program by integrating evidence from motif scanning and expression dynamics. PLOS Comput Biol 4(3):e1000021.
16. Litvak V, et al. (2009) Function of C/EBPdelta in a regulatory circuit that discriminates between transient and persistent TLR4-induced signals. Nat Immunol 10(4):437–443.
17. Zak DE, et al. (2011) Systems analysis identifies an essential role for SHANK-associated RH domain-interacting protein (SHARPIN) in macrophage Toll-like receptor 2 (TLR2) responses. Proc Natl Acad Sci USA 108(28):11536–11541.
18. Gaucher D, et al. (2008) Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses. J Exp Med 205(13):3119–3131.
19. Querec TD, et al. (2009) Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 10(1):116–125.
20. Nakaya HI, et al. (2011) Systems biology of vaccination for seasonal influenza in humans. Nat Immunol 12(8):786–795.
21. Chaussabel D, et al. (2008) A modular analysis framework for blood genomics studies: Application to systemic lupus erythematosus. Immunity 29(1):150–164.
22. Banchereau R, et al. (2012) Host immune transcriptional profiles reflect the variability in clinical disease manifestations in patients with Staphylococcus aureus infections. PLoS ONE 7(4):e34390.
23. Skinner JA, et al. (2011) P01.06: Whole blood transcriptional monitoring of acute HIV-1 infection reveals differential signatures of host immune activation. AIDS Res Hum Retroviruses 27(10):A1–A148.
24. Sangro B, et al. (2004) Phase I trial of intratumoral injection of an adenovirus encoding interleukin-12 for advanced digestive tumors. J Clin Oncol 22(8):1389–1397.
25. Shi C, Pamer EG (2011) Monocyte recruitment during infection and inflammation. Nat Rev Immunol 11(11):762–774.
26. Wu Z, et al. (2008) Memory T cell RNA rearrangement programmed by heterogeneous nuclear ribonucleoprotein hnRNPLL. Immunity 29(6):863–875.
27. Cline MS, et al. (2007) Integration of biological networks and gene expression data using Cytoscape. Nat Protoc 2(10):2366–2382.
28. Mathew PA, et al. (2004) The LLT1 receptor induces IFN-gamma production by human natural killer cells. Mol Immunol 40(16):1157–1163.
29. Wang N, et al. (2010) Cutting edge: The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-dependent NK cell functions in the C57BL/6 mouse. J Immunol 185(10):5683–5687.
30. Aldhamen YA, et al. (2011) Expression of the SLAM family of receptors adapter EAT-2 as a novel strategy for enhancing beneficial immune responses to vaccine antigens. J Immunol 186(2):722–732.
31. Pulendran B (2009) Learning immunology from the yellow fever vaccine: Innate immunity to systems vaccinology. Nat Rev Immunol 9(10):741–747.
32. Querec T, et al. (2006) Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J Exp Med 203(2): 413–424.
33. Cruz-Munoz ME, Dong Z, Shi X, Zhang S, Veillette A (2009) Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function. Nat Immunol 10(3):297–305.
34. Mellor A (2005) Indoleamine 2,3 dioxygenase and regulation of T cell immunity. Biochem Biophys Res Commun 338(1):20–24.
35. Liao X, et al. (2011) Krüppel-like factor 4 regulates macrophage polarization. J Clin Invest 121(7):2736–2749.
36. Grosse J, et al. (2006) Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease. Blood 107(8):3350–3358.
37. Shi L, Perin JC, Leipzig J, Zhang Z, Sullivan KE (2011) Genome-wide analysis of interferon regulatory factor I binding in primary human monocytes. Gene 487(1): 21–28.
38. Chen X, et al. (2008) Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell 133(6):1106–1117.
39. Liao W, et al. (2008) Priming for T helper type 2 differentiation by interleukin 2-mediated induction of interleukin 4 receptor alpha-chain expression. Nat Immunol 9 (11):1288–1296.
40. Perreau M, Pantaleo G, Kremer EJ (2008) Activation of a dendritic cell-T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells. J Exp Med 205(12):2717–2725.
41. Corey L, McElrath MJ, Kublin JG (2009) Post-step modifications for research on HIV vaccines. AIDS 23(1):3–8.
42. Benlahrech A, et al. (2009) Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1. Proc Natl Acad Sci USA 106(47):19940–19945.
43. Barnabas RV, et al.; NIAID HIV Vaccine Trials Network (2011) Impact of herpes simplex virus type 2 on HIV-1 acquisition and progression in an HIV vaccine trial (the Step study). J Acquir Immune Defic Syndr 57(3):238–244.
44. Curlin ME, et al. (2011) Serological immunity to adenovirus serotype 5 is not associated with risk of HIV infection: A case-control study. AIDS 25(2):153–158.
45. Frahm N, et al. (2012) Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine. J Clin Invest 122(1):359–367.
46. Haegel-Kronenberger H, et al. (2004) Inhibition of costimulation allows for repeated systemic administration of adenoviral vector in rhesus monkeys. Gene Ther 11(3): 241–252.
47. Loetscher P, Seitz M, Clark-Lewis I, Baggiolini M, Moser B (1994) Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes. FASEB J 8(13):1055–1060.
48. Kim JJ, et al. (1998) CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines. J Clin Invest 102(6):1112–1124.
49. Ouyang W, Rutz S, Crellin NK, Valdez PA, Hymowitz SG (2011) Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29:71–109.
50. Jewell NA, et al. (2010) Lambda interferon is the predominant interferon induced by influenza A virus infection in vivo. J Virol 84(21):11515–11522.
51. Kirchner J, Forbush KA, Bevan MJ (2001) Identification and characterization of thymus LIM protein: Targeted disruption reduces thymus cellularity. Mol Cell Biol 21 (24):8592–8604.
52. Fujii R, et al. (2002) Identification of a neuropeptide modified with bromine as an endogenous ligand for GPR7. J Biol Chem 277(37):34010–34016.
53. Sheets RL, et al. (2008) Biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (HIV-1), Ebola, or Marburg are similar despite differing adenovirus serotype vector, manufacturer’s construct, or gene inserts. J Immunotoxicol 5(3):315–335.
54. White LC, et al. (1996) Regulation of LMP2 and TAP1 genes by IRF-1 explains the paucity of CD8+ T cells in IRF-1-/- mice. Immunity 5(4):365–376.
55. Jin HT, Ahmed R, Okazaki T (2011) Role of PD-1 in regulating T-cell immunity. Curr Top Microbiol Immunol 350:17–37.
56. Mellor AL, Munn DH (2004) IDO expression by dendritic cells: Tolerance and tryptophan catabolism. Nat Rev Immunol 4(10):762–774.
57. Bull M, et al. (2007) Defining blood processing parameters for optimal detection of cryopreserved antigen-specific responses for HIV vaccine trials. J Immunol Methods 322(1–2):57–69.
58. Defawe OD, et al. (2012) Optimization and qualification of a multiplex bead array to assess cytokine and chemokine production by vaccine-specific cells. J Immunol Methods 382(1–2):117–128.
59. Hochberg Y (1988) A sharper Bonferroni procedure for multiple tests of significance. Biometrika 75:800–802.
60. Shiver JW, et al. (2002) Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415(6869):331–335.
61. Rice CM, Grakoui A, Galler R, Chambers TJ (1989) Transcription of infectious yellow fever RNA from full-length cDNA templates produced by in vitro ligation. New Biol 1 (3):285–296.
62. Bredenbeek PJ, et al. (2003) A stable full-length yellow fever virus cDNA clone and the role of conserved RNA elements in flavivirus replication. J Gen Virol 84(Pt 5): 1261–1268.
63. Franco D, et al. (2010) Evaluation of yellow fever virus 17D strain as a new vector for HIV-1 vaccine development. Vaccine 28(35):5676–5685.
64. Berry MP, et al. (2010) An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466(7309):973–977.
65. Lynn DJ, et al. (2008) InnateDB: Facilitating systems-level analyses of the mammalian innate immune response. Mol Syst Biol 4:218.
66. Chon SY, Hassanain HH, Pine R, Gupta SL (1995) Involvement of two regulatory elements in interferon-gamma-regulated expression of human indoleamine 2,3-dioxygenase gene. J Interferon Cytokine Res 15(6):517–526.
67. Ramsauer K, et al. (2007) Distinct modes of action applied by transcription factors STAT1 and IRF1 to initiate transcription of the IFN-gamma-inducible gbp2 gene. Proc Natl Acad Sci USA 104(8):2849–2854.
68. Conte E, et al. (2003) Involvement of interferon regulatory factor-1 in monocyte CD95 expression and CD95-mediated apoptosis. Cell Death Differ 10(5):615–617.