Immune recognition of gene transfer vectors: Focus on adenovirus as a paradigm

Frontiers in Immunology

Volumn 2, Issue SEP, 2011, Pages

  Aldhamen, Yasser Ali ^a   Seregin, Sergey ^a   Amalfitano, Andrea ^a,b  

^a Michigan State University ^*  (United States)

^b MICHIGAN STATE UNIVERSITY   (United States)

Author keywords

Adaptive immunity; Adenovirus; Cellular responses; Humoral responses; Innate immunity; Vaccines

Indexed keywords

EID: 84868585547     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2011.00040     Document Type: Review

References (153)

1. Abbink, P., Lemckert, A. A., Ewald, B. A., Lynch, D. M., Denholtz, M., Smits, S., Holterman, L., Damen, I., Vogels, R., Thorner, A. R., O'Brien, K. L., Carville, A., Mansfield, K. G., Goudsmit, J., Havenga, M. J., and Barouch, D. H. (2007). Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D. J. Virol. 81, 4654-4663.
2. Aldhamen, Y. A., Appledorn, D. M., Seregin, S. S., Liu, C. J., Schuldt, N. J., Godbehere, S., and Amalfitano, A. (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, 722-732.
3. Amalfitano, A. (2004). Utilization of adenovirus vectors for multiple gene transfer applications. Methods 33, 173-178.
4. Amalfitano, A., Hauser, M. A., Hu, H., Serra, D., Begy, C. R., and Chamberlain, J. S. (1998). Production and characterization of improved adenovirus vectors with the E1, E2b, and E3 genes deleted. J. Virol. 72, 926-933.
5. Amalfitano, A., and Parks, R. J. (2002). Separating fact from fiction: assessing the potential of modified adenovirus vectors for use in human gene therapy. Curr. Gene Ther. 2, 111-133.
6. Appledorn, D. M., Aldhamen, Y. A., Depas, W., Seregin, S. S., Liu, C. J., Schuldt, N., Quach, D., Quiroga, D., Godbehere, S., Zlatkin, I., Kim, S., McCormick, J. J., and Amalfitano, A. (2010). A new adenovirus based vaccine vector expressing an Eimeria tenella derived TLR agonist improves cellular immune responses to an antigenic target. PLoS ONE 5, e9579. doi: 10.1371/journal.pone. 0009579.
7. Appledorn, D. M., Aldhamen, Y. A., Godbehere, S., Seregin, S. S., and Amalfitano, A. (2011). Sublingual administration of an adenovirus serotype 5 (Ad5)based vaccine confirms toll-like receptor agonist activity in the oral cavity and elicits improved mucosal and systemic cell-mediated responses against HIV antigens despite preexisting Ad5 immunity. Clin. Vaccine Immunol. 18, 150-160.
8. Appledorn, D. M., Kiang, A., McBride, A., Jiang, H., Seregin, S., Scott, J. M., Stringer, R., Kousa, Y., Hoban, M., Frank, M. M., and Amalfitano, A. (2008a). Wild-type adenoviruses from groups A-F evoke unique innate immune responses, of which HAd3 and SAd23 are partially complement dependent. Gene Ther. 5, 885-901.
9. Appledorn, D. M., McBride, A., Seregin, S., Scott, J. M., Schuldt, N., Kiang, A., Godbehere, S., and Amalfitano, A. (2008b). Complex interactions with several arms of the complement system dictate innate and humoral immunity to adenoviral vectors. Gene Ther. 15, 1606-1617.
10. Appledorn, D. M., Patial, S., McBride, A., Godbehere, S., Van Rooijen, N., Parameswaran, N., and Amalfitano, A. (2008c). Adenovirus vectorinduced innate inflammatory mediators, MAPK signaling, as well as adaptive immune responses are dependent upon both TLR2 and TLR9 in vivo. J. Immunol. 181, 2134-2144.
11. Appledorn, D. M., Patial, S., Godbehere, S., Parameswaran, N., and Amalfitano, A. (2009). TRIF, and TRIF-interacting TLRs differentially modulate several adenovirus vectorinduced immune responses. J. Innate Immun. 1, 376-388.
12. Atencio, I. A., Grace, M., Bordens, R., Fritz, M., Horowitz, J. A., Hutchins, B., Indelicato, S., Jacobs, S., Kolz, K., Maneval, D., Musco, M. L., Shinoda, J., Venook, A., Wen, S., and Warren, R. (2006). Biological activities of a recombinant adenovirus p53 (SCH 58500) administered by hepatic arterial infusion in a Phase 1 colorectal cancer trial. Cancer Gene Ther. 13, 169-181.
13. Barlan, A. U., Griffin, T. M., McGuire, K. A., and Wiethoff, C. M. (2011). Adenovirus membrane penetration activates the NLRP3 inflammasome. J. Virol. 85, 146-155.
14. Barouch, D. H. (2008). Challenges in the development of an HIV-1 vaccine. Nature 455, 613-619.
15. Barouch, D. H. (2010). Novel adenovirus vector-based vaccines for HIV-1. Curr. Opin. HIV AIDS 5, 386-390.
16. Barouch, D. H., Kik, S. V., Weverling, G. J., Dilan, R., King, S. L., Maxfield, L. F., Clark, S., Ng'ang'a, D., Brandariz, K. L., Abbink, P., Sinangil, F., de Bruyn, G., Gray, G. E., Roux, S., Bekker, L. G., Dilraj, A., Kibuuka, H., Robb, M. L., Michael, N. L., Anzala, O., Amornkul, P. N., Gilmour, J., Hural, J., Buchbinder, S. P., Seaman, M. S., Dolin, R., Baden, L. R., Carville A. Mansfield K. G. Pau M. G., and Goudsmit, J. (2011). International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine 29, 5203-5209.
17. Barouch, D. H., Pau, M. G., Custers, J. H., Koudstaal, W., Kostense, S., Havenga, M. J., Truitt, D. M., Sumida, S. M., Kishko, M. G., Arthur, J. C., Korioth-Schmitz, B., Newberg, M. H., Gorgone, D. A., Lifton, M. A., Panicali, D. L., Nabel, G. J., Letvin, N. L., and Goudsmit, J. (2004). Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity. J. Immunol. 172, 6290-6297.
18. Basner-Tschakarjan, E., Gaffal, E., O'Keeffe, M., Tormo, D., Limmer, A., Wagner, H., Hochrein, H., and Tüting, T. (2006). Adenovirus efficiently transduces plasmacytoid dendritic cells resulting in TLR9-dependent maturation and IFN-alpha production. J. Gene Med. 8, 1300-1306.
19. Bergelson, J. M., Cunningham, J. A., Droguett, G., Kurt-Jones, E. A., Krithivas, A., Hong, J. S., Horwitz, M. S., Crowell, R. L., and Finberg, R. W. (1997). Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275, 1320-1323.
20. Blom, A. M., and Ram, S. (2008). Contribution of interactions between complement inhibitor C4b-binding protein and pathogens to their ability to establish infection with particular emphasis on Neisseria gonorrhoeae. Vaccine 26(Suppl. 8), I49-I55.
21. Bristol, J. A., Shirley, P., Idamakanti, N., Kaleko, M., and Connelly, S. (2000). In vivo dose threshold effect of adenovirus-mediated factor VIII gene therapy in hemophiliac mice. Mol. Ther. 2, 223-232.
22. Brunetti-Pierri, N., and Ng, P. (2009). Progress towards liver and lungdirected gene therapy with helperdependent adenoviral vectors. Curr. Gene Ther. 9, 329-340.
23. Brunetti-Pierri, N., Palmer, D. J., Beaudet, A. L., Carey, K. D., Finegold, M., and Ng, P. (2004). Acute toxicity after high-dose systemic injection of helper-dependent adenoviral vectors into nonhuman primates. Hum. Gene Ther. 15, 35-46.
24. Buchbinder, S. P., Mehrotra, D. V., Duerr, A., Fitzgerald, D. W., Mogg, R., Li, D., Gilbert, P. B., Lama, J. R., Marmor, M., Del Rio, C., McElrath, M. J., Casimiro, D. R., Gottesdiener, K. M., Chodakewitz, J. A., Corey, L., Robertson, M. N., and Step Study Protocol Team. (2008). Efficacy assessment of a cellmediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372, 1881-1893.
25. Burckstummer, T., Baumann, C., Blüml, S., Dixit, E., Dürnberger, G., Jahn, H., Planyavsky, M., Bilban, M., Colinge, J., Bennett, K. L., and SupertiFurga, G. (2009). An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome. Nat. Immunol. 10, 266-272.
26. Cerullo, V., Seiler, M. P., Mane, V., Brunetti-Pierri, N., Clarke, C., Bertin, T. K., Rodgers, J. R., and Lee, B. (2007). Toll-like receptor 9 triggers an innate immune response to helper-dependent adenoviral vectors. Mol. Ther. 15, 378-385.
27. Choi, I. K., Lee, J. S., Zhang, S. N., Park, J., Lee, K. M., Sonn, C. H., and Yun, C. O. (2011). Oncolytic adenovirus co-expressing IL-12 and IL18 improves tumor-specific immunity via differentiation of T cells expressing IL-12Rß2 or IL-18Ra. Gene Ther. doi: 10.1038/gt.2011.37. [Epub ahead of print].
28. Clarke, J. M., Morse, M. A., Lyerly, H. K., Clay, T., and Osada, T. (2010). Adenovirus vaccine immunotherapy targeting WT1-expressing tumors. Expert Opin. Biol. Ther. 10, 875-883.
29. Di Paolo, N. C., Miao, E. A., Iwakura, Y., Murali-Krishna, K., Aderem, A., Flavell, R. A., Papayannopoulou, T., and Shayakhmetov, D. M. (2009). Virus binding to a plasma membrane receptor triggers interleukin1 alpha-mediated proinflammatory macrophage response in vivo. Immunity 31, 110-121.
30. Ding, E. Y., Hodges, B. L., Hu, H., McVie-Wylie, A. J., Serra, D., Migone, F. K., Pressley, D., Chen, Y. T., and Amalfitano, A. (2001). Longterm efficacy after [E1-, polymerase] adenovirus-mediated transfer of human acid-alpha-glucosidase gene into glycogen storage disease type II knockout mice. Hum. Gene Ther. 12, 955-965.
31. Engelhardt, J. F., Ye, X., Doranz, B., and Wilson, J. M. (1994). Ablation of E2A in recombinant adenoviruses improves transgene persistence and decreases inflammatory response in mouse liver. Proc. Natl. Acad. Sci. U.S.A. 91, 6196-6200.
32. Everett, R. S., Hodges, B. L., Ding, E. Y., Xu, F., Serra, D., and Amalfitano, A. (2003). Liver toxicities typically induced by first-generation adenoviral vectors can be reduced by use of E1, E2b-deleted adenoviral vectors. Hum. Gene Ther. 14, 1715-1726.
33. Fernandes-Alnemri, T., Yu, J. W., Datta, P., Wu, J., and Alnemri, E. S. (2009). AIM2 activates the inflammasome and cell death in response to cytoplasmic DNA. Nature 458, 509-513.
34. Gabitzsch, E. S., Xu, Y., Balcaitis, S., Balint, J. P. Jr., and Jones, F. R. (2011). An Ad5[E1-, E2b-]HER2/neu vector induces immune responses and inhibits HER2/neu expressing tumor progression inAd5 immune mice. Cancer Gene Ther. 18, 326-335.
35. Gabitzsch, E. S., Xu, Y., Balint, J. P. Jr., Hartman, Z. C., Lyerly, H. K., and Jones, F. R. (2010). Anti-tumor immunotherapy despite immunity to adenovirus using a novel adenoviral vector Ad5 [E1-, E2b-]-CEA. Cancer Immunol. Immunother. 59, 1131-1135.
36. Gabitzsch, E. S., Xu, Y., Yoshida, L. H., Balint, J., Amalfitano, A., and Jones, F. R. (2009). Novel Adenovirus type 5 vaccine platform induces cellular immunity against HIV-1 Gag, Pol, Nef despite the presence of Ad5 immunity. Vaccine 27, 6394-6398.
37. Gabitzsch, E. S., Xu, Y., Yoshida, L. H., Balint, J., Gayle, R. B., Amalfitano, A., and Jones, F. R. (2009b). A preliminary and comparative evaluation of a novel Ad5 [E1-, E2b-] recombinant-based vaccine used to induce cell mediated immune responses. Immunol. Lett. 122, 44-51.
38. Gall, J. G., Crystal, R. G., and FalckPedersen, E. (1998). Construction and characterization of hexonchimeric adenoviruses: specification of adenovirus serotype. J. Virol. 72, 10260-10264.
39. Geisbert, T. W., Bailey, M., Hensley, L., Asiedu, C., Geisbert, J., Stanley, D., Honko, A., Johnson, J., Mulangu, S., Pau, M. G., Custers, J., Vellinga, J., Hendriks, J., Jahrling, P., Roederer, M., Goudsmit, J., Koup, R., and Sullivan, N. J. (2011). Recombinant adenovirus serotype 26 (Ad26) and Ad35 vaccine vectors bypass immunity to Ad5 and protect nonhuman primates against ebolavirus challenge. J. Virol. 85, 4222-4233.
40. Girardin, S. E., Sansonetti, P. J., and Philpott, D. J. (2002). Intracellular vs extracellular recognition of pathogens - common concepts in mammals and flies. Trends Microbiol. 10, 193-199.
41. Hacein-Bey-Abina, S., Von Kalle, C., Schmidt, M., McCormack, M. P., Wulffraat, N., Leboulch, P., Lim, A., Osborne, C. S., Pawliuk, R., Morillon, E., Sorensen, R., Forster, A., Fraser, P., Cohen, J. I., de Saint Basile, G., Alexander, I., Wintergerst, U., Frebourg, T., Aurias, A., Stoppa-Lyonnet, D., Romana, S., Radford-Weiss, I., Gross, F., Valensi, F., Delabesse, E., Macintyre, E., Sigaux, F., Soulier, J., Leiva, L. E., Wissler, M., Prinz, C., Rabbitts, T. H., Le Deist, F., Fischer, A., and Cavazzana-Calvo, M. (2003). LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302, 415-419.
42. Hartman, Z. C., Appledorn, D. M., and Amalfitano, A. (2008). Adenovirus vector induced innate immune responses: impact upon efficacy and toxicity in gene therapy and vaccine applications. Virus Res. 132, 1-14.
43. Hartman, Z. C., Kiang, A., Everett, R. S., Serra, D., Yang, X. Y., Clay, T. M., and Amalfitano, A. (2007). Adenovirus infection triggers a rapid, MyD88regulated transcriptome response critical to acute-phase and adaptive immune responses in vivo. J. Virol. 81, 1796-1812.
44. Hartman, Z. C., Osada, T., Glass, O., Yang, X. Y., Lei, G. J., Lyerly, H. K., and Clay, T. M. (2010). Ligand-independent toll-like receptor signals generated by ectopic overexpression of MyD88 generate local and systemic antitumor immunity. Cancer Res. 70, 7209-7220.
45. Haut, L. H., Ratcliffe, S., Pinto, A. R., and Ertl, H. (2011). Effect of preexisting immunity to adenovirus on transgene product-specific genital T cell responses on vaccination of mice with a homologous vector. J. Infect. Dis. 203, 1073-1081.
46. Heemskerk, B., Veltrop-Duits, L. A., van Vreeswijk, T., ten Dam, M. M., Heidt, S., Toes, R. E., van Tol, M. J., and Schilham, M. W. (2003). Extensive cross-reactivity of CD4+ adenovirus-specific T cells: implications for immunotherapy and gene therapy. J. Virol. 77, 6562-6566.
47. Hensley, S. E., Giles-Davis, W., McCoy, K. C., Weninger, W., and Ertl, H. C. (2005). Dendritic cell maturation, but not CD8+ T cell induction, isdependentontypeIIFN signaling during vaccination with adenovirus vectors. J. Immunol. 175, 6032-6041.
48. Hoffmann, J. A., Kafatos, F. C., Janeway, C. A., and Ezekowitz, R. A. (1999). Phylogenetic perspectives in innate immunity. Science 284, 1313-1318.
49. Hornung, V., Ablasser, A., CharrelDennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E., and Fitzgerald, K. A. (2009). AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514-518.
50. Howe, S. J., Mansour, M. R., Schwarzwaelder, K., Bartholomae, C., Hubank, M., Kempski, H., Brugman, M. H., Pike-Overzet, K., Chatters, S. J., de Ridder, D., Gilmour, K. C., Adams, S., Thornhill, S. I., Parsley, K. L., Staal, F. J., Gale, R. E., Linch, D. C., Bayford, J., Brown, L., Quaye, M., Kinnon, C., Ancliff, P., Webb, D. K., Schmidt, M., von Kalle, C., Gaspar, H. B., and Thrasher, A. J. (2008). Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCIDX1 patients. J. Clin. Invest. 118, 3143-3150.
51. Huang P. I., Chang J. F., Kirn D. H., and Liu, T. C. (2009). Targeted genetic and viral therapy for advanced head and neck cancers. Drug Discov. Today 14, 570-578.
52. Huang, S., Kamata, T., Takada, Y., Ruggeri, Z. M., and Nemerow, G. R. (1996). Adenovirus interaction with distinct integrins mediates separate events in cell entry and gene deliverytohematopoieticcells.J. Virol. 70, 4502-4508.
53. Huarte, E., Larrea, E., HernándezAlcoceba, R., Alfaro, C., Murillo, O., Arina, A., Tirapu, I., Azpilicueta, A., Hervás-Stubbs, S., Bortolanza, S., Pérez-Gracia, J. L., Civeira, M. P., Prieto, J., Riezu-Boj, J. I., and Melero, I. (2006). Recombinant adenoviral vectors turn on the type I interferon system without inhibition of transgene expression and viral replication. Mol. Ther. 14, 129-138.
54. Hutnick, N. A., Carnathan, D., Demers, K., Makedonas, G., Ertl, H. C., and Betts, M. R. (2010). Adenovirusspecific human T cells are pervasive, polyfunctional, and cross-reactive. Vaccine 28, 1932-1941.
55. Ishii, K. J., and Akira, S. (2006). Innate immune recognition of, and regulation by, DNA. Trends Immunol. 27, 525-532.
56. Ishii, K. J., Kawagoe, T., Koyama, S., Matsui, K., Kumar, H., Kawai, T., Uematsu, S., Takeuchi, O., Takeshita, F., Coban, C., and Akira, S. (2008). TANK-binding kinase1 delineates innate and adaptive immune responses to DNA vaccines. Nature 451, 725-729.
57. Jiang, H., Wang, Z., Serra, D., Frank, M. M., and Amalfitano, A. (2004). Recombinant adenovirus vectors activate the alternative complement pathway, leading to the binding of human complement protein C3 independent of anti-ad antibodies. Mol. Ther. 10, 1140-1142.
58. Johansson, C., Jonsson, M., Marttila, M., Persson, D., Fan, X. L., Skog, J., Frängsmyr, L., Wadell, G., and Arnberg, N. (2007). Adenoviruses use lactoferrin as a bridge for CARindependent binding to and infection of epithelial cells. J. Virol. 81, 954-963.
59. Joshi, A., Tang, J., Kuzma, M., Wagner, J., Mookerjee, B., Filicko, J., Carabasi, M., Flomenberg, N., and Flomenberg, P. (2009). Adenovirus DNA polymerase is recognized by human CD8+ T cells. J. Gen. Virol. 90(Pt 1), 84-94.
60. Kanneganti, T. D. (2010). Central roles of NLRs and inflammasomes in viral infection. Nat. Rev. Immunol. 10, 688-698.
61. Kawai, T., and Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat. Immunol. 11, 373-384.
62. Kiang, A., Hartman, Z. C., Everett, R. S., Serra, D., Jiang, H., Frank, M. M., and Amalfitano, A. (2006a). Multiple innate inflammatory responses induced after systemic adenovirus vector delivery depend on a functional complement system. Mol. Ther. 14, 588-598.
63. Kiang, A., Hartman, Z. C., Liao, S., Xu, F., Serra, D., Palmer, D. J., Ng, P., and Amalfitano, A. (2006b). Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice. Mol. Ther. 13, 127-134.
64. Krause, A., Joh, J. H., Hackett, N. R., Roelvink, P. W., Bruder, J. T., Wickham, T. J., Kovesdi, I., Crystal, R. G., and Worgall, S. (2006). Epitopes expressed in different adenovirus capsid proteins induce different levels of epitope-specific immunity. J. Virol. 80, 5523-5530.
65. Lasaro, M. O., and Ertl, H. C. (2009). New insights on adenovirus as vaccine vectors. Mol. Ther. 17, 1333-1339.
66. Lee, S. G., Yoon, S. J., Kim, C. D., Kim, K., Lim, D. S., Yeom, Y. I., Sung, M. W., Heo, D. S., Kim, N. K. (2000). Enhancement of adenoviral transduction with polycationic liposomes in vivo. Cancer Gene Ther. 7, 1329-1335.
67. Leen, A. M., Sili, U., Vanin, E. F., Jewell, A. M., Xie, W., Vignali, D., Piedra, P. A., Brenner, M. K., and Rooney, C. M. (2004). Conserved CTL epitopes on the adenovirus hexon protein expand subgroup cross-reactive and subgroup-specific CD8+ T cells. Blood 104, 2432-2440.
68. Li, E., Stupack, D., Klemke, R., Cheresh, D. A., and Nemerow, G. R. (1998). Adenovirus endocytosis via alpha(v) integrins requires phosphoinositide3-OH kinase. J. Virol. 72, 2055-2061.
69. Lichtenstein, D. L., and Wold, W. S. (2004). Experimental infections of humans with wild-type adenoviruses and with replicationcompetent adenovirus vectors: replication, safety, and transmission. Cancer Gene Ther. 11, 819-829.
70. Lieber, A., He, C. Y., Meuse, L., Schowalter, D., Kirillova, I., Winther, B., and Kay, M. A. (1997). The role of Kupffer cell activation and viral gene expression in early liver toxicity after infusion of recombinant adenovirus vectors. J. Virol. 71, 8798-8807.
71. Lindsay, R. W., Darrah, P. A., Quinn, K. M., Wille-Reece, U., Mattei, L. M., Iwasaki, A., Kasturi, S. P., Pulendran, B., Gall, J. G., Spies, A. G., and Seder, R. A. (2010). CD8+ T cell responses following replication-defective adenovirus serotype 5 immunization are dependent on CD11c+ dendritic cells but show redundancy in their requirement of TLR and nucleotide-binding oligomerization domain-like receptor signaling. J. Immunol. 185, 1513-1521.
72. Liu, J., Ewald, B. A., Lynch, D. M., Denholtz, M., Abbink, P., Lemckert, A.
73. A., Carville, A., Mansfield, K. G., Havenga, M. J., Goudsmit, J., and Barouch, D. H. (2008). Magnitude and phenotype of cellular immune responses elicited by recombinant adenovirus vectors and heterologous prime-boost regimens in rhesus monkeys. J. Virol. 82, 4844-4852.
74. Liu, J., O'Brien, K. L., Lynch, D. M., Simmons, N. L., La Porte, A., Riggs, A. M., Abbink, P., Coffey, R. T., Grandpre, L. E., Seaman, M. S., Landucci, G., Forthal, D. N., Montefiori, D. C., Carville, A., Mansfield, K. G., Havenga, M. J., Pau, M. G., Goudsmit, J., and Barouch, D. H. (2009). Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature 457, 87-91.
75. Liu, M. A. (2010). Immunologic basis of vaccine vectors. Immunity 33, 504-515.
76. Liu, Z. X., Govindarajan, S., Okamoto, S., and Dennert, G. (2000). NK cells cause liver injury and facilitate the induction of T cell-mediated immunity to a viral liver infection. J. Immunol. 164, 6480-6486.
77. Lore, K., Adams, W. C., Havenga, M. J., Precopio, M. L., Holterman, L., Goudsmit, J., and Koup, R. A. (2007). Myeloid and plasmacytoid dendritic cells are susceptible to recombinant adenovirus vectors and stimulate polyfunctional memory T cell responses. J. Immunol. 179, 1721-1729.
78. Lotze, M. T., and Tracey, K. J. (2005). High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat. Rev. Immunol. 5, 331-342.
79. Matsuda, N., and Hattori, Y. (2006). Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy. J. Pharmacol. Sci. 101, 189-198.
80. Matthews, C., Jenkins, G., Hilfinger, J., and Davidson, B. (1999). Poly-l-lysine improves gene transfer with adenovirus formulated in PLGA microspheres. Gene Ther. 6, 1558-1564.
81. McCaffrey, A. P., Fawcett, P., Nakai, H., McCaffrey, R. L., Ehrhardt, A., Pham, T. T., Pandey, K., Xu, H., Feuss, S., Storm, T. A., and Kay, M. A. (2008). The host response to adenovirus, helper-dependent adenovirus, and adeno-associated virus in mouse liver. Mol. Ther. 16, 931-941.
82. McConnell, M. J., Hanna, P. C., and Imperiale, M. J. (2006). Cytokine response and survival of mice immunized with an adenovirus expressing Bacillus anthracis protective antigen domain 4. Infect. Immun. 74, 1009-1015.
83. McCoy, K., Tatsis, N., Korioth-Schmitz, B., Lasaro, M. O., Hensley, S. E., Lin, S. W., Li, Y., Giles-Davis, W., Cun, A., Zhou, D., Xiang, Z., Letvin, N. L., and Ertl, H. C. (2007). Effect of preexisting immunity to adenovirus human serotype 5 antigens on the immune responses of nonhuman primates to vaccine regimens based on humanor chimpanzee-derived adenovirus vectors. J. Virol. 81, 6594-6604.
84. Medzhitov, R. (2007). Recognition of microorganisms and activation of the immune response. Nature 449, 819-826.
85. Minamitani, T., Iwakiri, D., and Takada, K. (2011). Adenovirus virus-associated RNAs induce type I interferon expression through a RIG-I-mediated pathway. J. Virol. 85, 4035-4040.
86. Modlich, U. Kustikova, O. S., Schmidt, M., Rudolph, C., Meyer, J., Li, Z., Kamino, K., von Neuhoff, N., Schlegelberger, B., Kuehlcke, K., Bunting, K. D., Schmidt, S., Deichmann, A., von Kalle, C., Fehse, B., and Baum, C. (2005). Leukemias following retroviral transfer of multidrug resistance 1 (MDR1) are driven by combinatorial insertional mutagenesis. Blood 105, 4235-4246.
87. Molinier-Frenkel, V., Gahery-Segard, H., Mehtali, M., Le Boulaire, C., Ribault, S., Boulanger, P., Tursz, T., Guillet, J. G., and Farace, F. (2000). Immune response to recombinant adenovirus in humans: capsid components from viral input are targets for vector-specific cytotoxic T lymphocytes. J. Virol. 74, 7678-7682.
88. Molinier-Frenkel, V., Lengagne, R., Gaden, F., Hong, S. S., Choppin, J., Gahery-Ségard, H., Boulanger, P., and Guillet, J. G. (2002). Adenovirus hexon protein is a potent adjuvant for activation of a cellular immune response. J. Virol. 76, 127-135.
89. Morral, N., O'Neal, W. K., Rice, K., Leland, M. M., Piedra, P. A., AguilarCórdova, E., Carey, K. D., Beaudet, A. L., and Langston, C. (2002). Lethal toxicity, severe endothelial injury, and a threshold effect with high doses of an adenoviral vector in baboons. Hum. Gene Ther. 13, 143-154.
90. Morral, N., Parks, R. J., Zhou, H., Langston, C., Schiedner, G., Quinones, J., Graham, F. L., Kochanek, S., and Beaudet, A. L. (1998). High doses of a helperdependent adenoviral vector yield supraphysiological levels of alpha1antitrypsin with negligible toxicity. Hum. Gene Ther. 9, 2709-2716.
91. Muruve, D. A., Pétrilli, V., Zaiss, A. K., White, L. R., Clark, S. A., Ross, P. J., Parks, R. J., and Tschopp, J. (2008). The inflammasome recognizes cytosolic microbial and host DNA and triggers an innate immune response. Nature 452, 103-107.
92. Nemerow, G. R., and Stewart, P. L. (1999). Role of alpha(v) integrins in adenovirus cell entry and gene delivery. Microbiol. Mol. Biol. Rev. 63, 725-734.
93. Nociari, M., Ocheretina, O., Schoggins, J. W., and Falck-Pedersen, E. (2007). Sensing infection by adenovirus: toll-like receptor-independent viral DNA recognition signals activation of the interferon regulatory factor 3 master regulator. J. Virol. 81, 4145-4157.
94. O'Neill, L. A., and Bowie, A. G. (2010). Sensing and signaling in antiviral innate immunity. Curr. Biol. 20, R328-R333.
95. O'Riordan, C. R., Lachapelle, A., Delgado, C., Parkes, V., Wadsworth, S. C., Smith, A. E., and Francis, G. E. (1999). PEGylation of adenovirus with retention of infectivity and protection from neutralizing antibody in vitro and in vivo. Hum. Gene Ther. 10, 1349-1358.
96. Osada, T., Yang, X. Y., Hartman, Z. C., Glass, O., Hodges, B. L., Niedzwiecki, D., Morse, M. A., Lyerly, H. K., Amalfitano, A., and Clay, T. M. (2009). Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity. Cancer Gene Ther. 16, 673-682.
97. Otake, K., Ennist, D. L., Harrod, K., and Trapnell, B. C. (1998). Nonspecific inflammation inhibits adenovirusmediated pulmonary gene transfer and expression independent of specific acquired immune responses. Hum. Gene Ther. 9, 2207-2222.
98. Parker, A. L., Waddington, S. N., Buckley, S. M., Custers, J., Havenga, M. J., van Rooijen, N., Goudsmit, J., McVey, J. H., Nicklin, S. A., and Baker, A. H. (2009). Effect of neutralizing sera on factor x-mediated adenovirus serotype 5 gene transfer. J. Virol. 83, 479-483.
99. Parks, R. J. (2005). Adenovirus protein IX: a new look at an old protein. Mol. Ther. 11, 19-25.
100. Parks, R. J., Chen, L., Anton, M., Sankar, U., Rudnicki, M. A., and Graham, F. L. (1996). A helper-dependent adenovirus vector system: removal of helper virus by Cre-mediated excision of the viral packaging signal. Proc. Natl. Acad. Sci. U.S.A. 93, 13565-13570.
101. Peng, Y., Falck-Pedersen, E., and Elkon, K. B. (2001). Variation in adenovirus transgene expression between BALB/c and C57BL/6 mice is associated with differences in interleukin-12 and gamma interferon production and NK cell activation. J. Virol. 75, 4540-4550.
102. Philpott, N. J., Nociari, M., Elkon, K. B., and Falck-Pedersen, E. (2004). Adenovirus-induced maturation of dendritic cells through a PI3 kinase-mediated TNF-alpha induction pathway. Proc. Natl. Acad. Sci. U.S.A. 101, 6200-6205.
103. Pichla-Gollon, S. L., Lin, S. W., Hensley, S. E., Lasaro, M. O., HerkenhoffHaut, L., Drinker, M., Tatsis, N., Gao, G. P., Wilson, J. M., Ertl, H. C., and Bergelson, J. M. (2009). Effect of preexisting immunity on an adenovirus vaccine vector: in vitro neutralization assays fail to predict inhibition by antiviral antibody in vivo. J. Virol. 83, 5567-5573.
104. Priddy, F. H., Brown, D., Kublin, J., Monahan, K., Wright, D. P., Lalezari, J., Santiago, S., Marmor, M., Lally, M., Novak, R. M., Brown, S. J., Kulkarni, P., Dubey, S. A., Kierstead, L. S., Casimiro, D. R., Mogg, R., DiNubile, M. J., Shiver, J.W., Leavitt, R. Y., Robertson, M. N., Mehrotra, D. V., Quirk, E., and Merck V520016 Study Group. (2008). Safety and immunogenicity of a replicationincompetent adenovirus type 5 HIV1 clade B gag/pol/nef vaccine in healthy adults. Clin. Infect. Dis. 46, 1769-1781.
105. Raper, S. E., Chirmule, N., Lee, F. S., Wivel, N. A., Bagg, A., Gao, G. P., Wilson, J. M., and Batshaw, M. L. (2003). Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. Mol. Genet. Metab. 80, 148-158.
106. Raper, S. E., Haskal, Z. J., Ye, X., Pugh, C., Furth, E. E., Gao, G. P., and Wilson, J. M. (1998). Selective gene transfer into the liver of non-human primates with E1deleted, E2A-defective, or E1-E4 deleted recombinant adenoviruses. Hum. Gene Ther. 9, 671-679.
107. Raper, S. E., Yudkoff, M., Chirmule, N., Gao, G. P., Nunes, F., Haskal, Z. J., Furth, E. E., Propert, K. J., Robinson, M. B., Magosin, S., Simoes, H., Speicher, L., Hughes, J., Tazelaar, J., Wivel, N. A., Wilson, J. M., and Batshaw, M. L. (2002). A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum. Gene Ther. 13, 163-175.
108. Rathinam, V. A., Jiang, Z., Waggoner, S. N., Sharma, S., Cole, L. E., Waggoner, L., Vanaja, S. K., Monks, B. G., Ganesan, S., Latz, E., Hornung, V., Vogel, S. N., Szomolanyi-Tsuda, E., and Fitzgerald, K. A. (2010). The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 11, 395-402.
109. Reay, J., Kim, S. H., Lockhart, E., Kolls, J., and Robbins, P. D. (2009). Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response. Cancer Gene Ther. 16, 776-785.
110. Rhee, E. G. Blattman, J. N., Kasturi, S. P., Kelley, R. P., Kaufman, D. R., Lynch, D. M., La Porte, A., Simmons, N. L., Clark, S. L., Pulendran, B., Greenberg, P. D., and Barouch, D. H. (2011). Multiple innate immune pathways contribute to the immunogenicity of recombinant adenovirus vaccine vectors. J. Virol. 85, 315-323.
111. Ritter, T., Lehmann, M., and Volk, H. D. (2002). Improvements in gene therapy: averting the immune response to adenoviral vectors. BioDrugs 16, 3-10.
112. Roy, S., Shirley, P. S., McClelland, A., and Kaleko, M. (1998). Circumvention of immunity to the adenovirus major coat protein hexon. J. Virol. 72, 6875-6879.
113. Russell, W. C. (2009). Adenoviruses: update on structure and function. J. Gen. Virol. 90(Pt 1), 1-20.
114. Rux, J. J., and Burnett, R. M. (2004). Adenovirus structure. Hum. Gene Ther. 15, 1167-1176.
115. Ruzek, M. C., Kavanagh, B. F., Scaria, A., Richards, S. M., and Garman, R. D. (2002). Adenoviral vectors stimulate murine natural killer cell responses and demonstrate antitumor activities in the absence of transgene expression. Mol. Ther. 5, 115-124.
116. Schnell, M. A., Zhang, Y., Tazelaar, J., Gao, G. P., Yu, Q. C., Qian, R., Chen, S. J., Varnavski, A. N., LeClair, C., Raper, S. E., and Wilson, J. M. (2001). Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors. Mol. Ther. 3(Pt 1), 708-722.
117. Schroers, R., Hildebrandt, Y., Hasenkamp, J., Glass, B., Lieber, A., Wulf, G., and Piesche, M. (2004). Gene transfer into human T lymphocytes and natural killer cells by Ad5/F35 chimeric adenoviral vectors. Exp. Hematol. 32, 536-546.
118. Seregin, S. S., Aldhamen, Y. A., Appledorn, D. M., Hartman, Z. C., Schuldt, N. J., Scott, J., Godbehere, S., Jiang, H., Frank, M. M., and Amalfitano, A. (2010a). Adenovirus capsid-display of the retro-oriented human complement inhibitor DAF reduces Ad vector-triggered immune responses in vitro and in vivo. Blood 116, 1669-1677.
119. Seregin, S. S., Hartman, Z. C., Appledorn, D. M., Godbehere, S., Jiang, H., Frank, M. M., and Amalfitano, A. (2010b). Novel adenovirus vectors "capsid-displaying" a human complement inhibitor. J. Innate Immun. 2, 353-359.
120. Seregin, S. S., Aldhamen, Y. A., Appledorn, D. M., Zehnder, J., Voss, T., Godbehere, S., and Amalfitano, A. (2011). UseofDAF-displayingade-ovirusvectorsreducesinduction of transgene-andvector specific adaptiveimmuneresponsesin mice. Hum. GeneTher. doi:10.1089/hum.2010.218.[Epubahead of print].
121. Seregin, S. S., and Amalfitano, A. (2010). Improving Adenovirus based gene transfer: strategies to accomplish immune evasion. Viruses 2, 2013-2036.
122. Seregin, S. S., and Amalfitano, A (2009). Overcoming pre-existing adenovirus immunity by genetic engineering of adenovirus-based vectors. Expert Opin. Biol. Ther. 9, 1521-1531.
123. Seregin, S. S., Appledorn, D. M., McBride, A. J., Schuldt, N. J., Aldhamen, Y. A., Voss, T., Wei, J., Bujold, M., Nance, W., Godbehere, S., and Amalfitano, A. (2009). Transient pretreatment with glucocorticoid ablates innate toxicity of systemically delivered adenoviral vectors without reducing efficacy. Mol. Ther. 17, 685-696.
124. Shayakhmetov, D. M., Di Paolo, N. C., and Mossman, K. L. (2010). Recognition of virus infection and innate host responses to viral gene therapy vectors. Mol. Ther. 18, 1422-1429.
125. Shayakhmetov, D. M., Gaggar, A., Ni, S., Li, Z. Y., and Lieber, A. (2005). Adenovirus binding to blood factors results in liver cell infection and hepatotoxicity. J. Virol. 79, 7478-7491.
126. Shifrin, A. L., Chirmule, N., Zhang, Y., and Raper, S. E. (2005). Macrophage ablation attenuates adenoviral vector-induced pancreatitis. Surgery 137, 545-551.
127. Siddiqui, F., Li, C. Y., Larue, S. M., Poulson, J. M., Avery, P. R., Pruitt, A. F., Zhang, X., Ullrich, R. L., Thrall, D. E., Dewhirst, M. W., and Hauck, M. L. (2007). A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas. Mol. Cancer Ther. 6, 380-389.
128. Smith, J. G., Cassany, A., Gerace, L., Ralston, R., and Nemerow, G. R. (2008). Neutralizing antibody blocks adenovirus infection by arresting microtubule-dependent cytoplasmic transport. J. Virol. 82, 6492-6500.
129. St George, J. A. (2003). Gene therapy progress and prospects: adenoviral vectors. Gene Ther. 10, 1135-1141.
130. Sumida, S. M., Truitt, D. M., Kishko, M. G., Arthur, J. C., Jackson, S. S., Gorgone, D. A., Lifton, M. A., Koudstaal, W., Pau, M. G., Kostense, S., Havenga, M. J., Goudsmit, J., Letvin, N. L., and Barouch, D. H. (2004). Neutralizing antibodies and CD8+ T lymphocytes both contribute to immunity to adenovirus serotype 5 vaccine vectors. J. Virol. 78, 2666-2673.
131. Sumida, S. M., Truitt, D. M., Lemckert, A. A., Vogels, R., Custers, J. H., Addo, M. M., Lockman, S., Peter, T., Peyerl, F. W., Kishko, M. G., Jackson, S. S., Gorgone, D. A., Lifton, M. A., Essex, M., Walker, B. D., Goudsmit, J., Havenga, M. J., and Barouch, D. H. (2005). Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein. J. Immunol. 174,7179-7185.
132. Takaoka, A., Wang, Z., Choi, M. K., Yanai, H., Negishi, H., Ban, T., Lu, Y., Miyagishi, M., Kodama, T., Honda, K., Ohba, Y., and Taniguchi, T. (2007). DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 448, 501-505.
133. Takeuchi, O., and Akira, S. (2010). Pattern recognition receptors and inflammation. Cell 140, 805-820.
134. Tang, J., Lengagne, R., Gaden, F., Hong, S. S., Choppin, J., Gahery-Ségard, H., Boulanger, P., and Guillet, J. G. (2006). Human CD8+ cytotoxic T cell responses to adenovirus capsid proteins. Virology 350, 312-322.
135. Thorner, A. R., Lemckert, A. A., Goudsmit, J., Lynch, D. M., Ewald, B. A., Denholtz, M., Havenga, M. J., and Barouch, D. H. (2006). Immunogenicity of heterologous recombinant adenovirus prime-boost vaccine regimens is enhanced by circumventing vector cross-reactivity. J. Virol. 80, 12009-12016.
136. Tibbles, L. A., Spurrell, J. C., Bowen, G. P., Liu, Q., Lam, M., Zaiss, A. K., Robbins, S. M., Hollenberg, M. D., Wickham, T. J., and Muruve, D. A. (2002). Activation of p38 and ERK signaling during adenovirus vector cell entry lead to expression of the C-X-C chemokine IP-10. J. Virol. 76, 1559-1568.
137. Tripathy, S. K., Black, H. B., Goldwasser, E., and Leiden, J. M. (1996). Immune responses to transgeneencoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat. Med. 2, 545-550.
138. Tripathy, S. K., Goldwasser, E., Lu, M. M., Barr, E., and Leiden, J. M. (1994). Stable delivery of physiologic levels of recombinant erythropoietin to the systemic circulation by intramuscular injection of replication-defective adenovirus. Proc. Natl. Acad. Sci. U.S.A. 91, 11557-11561.
139. Urosevic, M., Fujii, K., Calmels, B., Laine, E., Kobert, N., Acres, B., and Dummer, R. (2007). Type I IFN innate immune response to adenovirus-mediated IFN-gamma gene transfer contributes to the regression of cutaneous lymphomas. J. Clin. Invest. 117, 2834-2846.
140. Vellinga, J., Van der Heijdt, S., and Hoeben, R. C. (2005). The adenovirus capsid: major progress in minor proteins. J. Gen. Virol. 86(Pt 6), 1581-1588.
141. Verdino, P., Witherden, D. A., Havran, W. L., and Wilson, I. A. (2010). The molecular interaction of CAR and JAML recruits the central cell signal transducer PI3K. Science 329, 1210-1214.
142. Waehler, R., Russell, S. J., and Curiel, D. T. (2007). Engineering targeted viral vectors for gene therapy. Nat. Rev. Genet. 8, 573-587.
143. Weaver, E. A., Nehete, P. N., Buchl, S. S., Senac, J. S., Palmer, D., Ng, P., Sastry, K. J., and Barry, M. A. (2009). Comparison of replicationcompetent, first generation, and helper-dependent adenoviral vaccines. PLoS ONE 4, e5059. doi: 10.1371/journal.pone.0005059.
144. Wickham, T. J., Mathias, P., Cheresh, D. A., and Nemerow, G. R. (1993). Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 73, 309-319.
145. Wilderman, M. J., Kim, S., Gillespie, C. T., Sun, J., Kapoor, V., Vachani, A., Sterman, D. H., Kaiser, L. R., Albelda, S. M. (2006). Blockade of TNF-alpha decreases both inflammation and efficacy of intrapulmonary Ad. IFNbeta immunotherapy in an orthotopic model of bronchogenic lung cancer. Mol. Ther. 13, 910-917.
146. Wilson, J. M. (2009). Lessons learned from the gene therapy trial for ornithine transcarbamylase deficiency. Mol. Genet. Metab. 96, 151-157.
147. Worgall, S., Krause, A., Rivara, M., Hee, K. K., Vintayen, E. V., Hackett, N. R., Roelvink, P. W., Bruder, J. T., Wickham, T. J., Kovesdi, I., and Crystal, R. G. (2005). Protection against P. aeruginosa with an adenovirus vector containing an OprF epitope in the capsid. J. Clin. Invest. 115, 1281-1289.
148. Wu, H., Dmitriev, I., Kashentseva, E., Seki, T., Wang, M., and Curiel, D. T. (2002). Construction and characterization of adenovirus serotype 5 packaged by serotype 3 hexon. J. Virol. 76, 12775-12782.
149. Zhang, Y., Chirmule, N., Gao, G. P., Qian, R., Croyle, M., Joshi, B., Tazelaar, J., and Wilson, J. M. (2001). Acute cytokine response to systemic adenoviral vectors in mice is mediated by dendritic cells and macrophages. Mol. Ther. 3(Pt 1), 697-707.
150. Zhu, J., Huang, X., and Yang, Y. (2007). Innate immune response to adenoviral vectors is mediated by both toll-like receptor-dependent and -independent pathways. J. Virol. 81, 3170-3180.
151. Zhu, J., Huang, X., and Yang, Y. (2008). A critical role for type I IFN-dependentNKcellactivationin innate immune elimination of adenoviral vectors in vivo. Mol. Ther. 16, 1300-1307.
152. Zhu, J., Huang, X., and Yang, Y. (2010). NKG2D is required for NK cell activation and function in response to E1-deleted adenovirus. J. Immunol. 185, 7480-7486.
153. Ziegler, R. J., Li, C., Cherry, M., Zhu, Y., Hempel, D., van Rooijen, N., Ioannou, Y. A., Desnick, R. J., Goldberg, M. A., Yew, N. S., and Cheng, S. H. (2002). Correction of the nonlinear dose response improves the viability of adenoviral vectors for gene therapy of Fabry disease. Hum. Gene Ther. 13, 935-945.