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The potential of a novel Adenovirus vector for vaccination

By Stuart Martin

Abstract

Adenoviruses (Ads) have many attractive characteristics for use as agents of genebased\ud vaccines and therapies. The most frequently used Ad vectors in preclinical\ud research are based on Ad5. However, in the clinical setting Ad5 vectors have severe\ud limitations. About 90% of the population have neutralising antibodies against Ad5\ud and infection requires expression of the viral receptor CAR, which is not present on\ud important cell types. Previous data from this laboratory suggested that the species D\ud adenovirus, Ad19a, may overcome some of these limitations. Most relevant for\ud vaccination is its high efficiency of infection of human dendritic cells (DCs), the\ud most important antigen presenting cells. This highly effective DC targeting was\ud retained in Ad19aGFP vectors. To investigate the potential of Ad19a vectors for\ud vaccination further, two transgenes, the nucleocapsid gene from pneumovirus of\ud mice (PVM-N), and a HIV polyprotein cassette (HIVA), were inserted into\ud replication-deficient Ad5 and Ad19a vectors using recombineering. rAd19aPVM and\ud rAd19aHIVA expressed a significantly higher amount of transgene compared with\ud their Ad5 homologues. Encouraging results were obtained when the ability of\ud rAd5PVM and rAd19aPVM to protect mice from lethal PVM challenge was\ud examined using various prime/boost vaccinations. A dose of 106 pfu of rAd19aPVM,\ud but not rAd5PVM, provided protection. rAd5PVM did, however, protect mice at the\ud same dose when combined with rAd19aPVM in a heterologous prime boost\ud schedule. Vaccination-induced IgG responses to PVM-N did not correlate with\ud protection, implicating cell-mediated immune responses in protection. Utilising\ud rAd19aGFP, evidence is also provided that Ad19a may use CD46 and to some extent\ud CAR as a receptor on CHO cells, expanding our knowledge of the basic biology of\ud this virus

Topics: QR355
OAI identifier: oai:wrap.warwick.ac.uk:34601

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Citations

  1. (2006). A
  2. (1992). A block in release of progeny virus and a high particle-to-infectious unit ratio contribute to poor growth of enteric adenovirus types 40 and 41 in cell culture.
  3. (1995). A human immunodeficiency virus 1 (HIV-1) clade A vaccine in clinical trials: stimulation of HIV-specific T-cell responses by DNA and recombinant modified vaccinia virus Ankara (MVA) vaccines in humans.
  4. (2006). A new group B adenovirus receptor is expressed at high levels on human stem and tumor cells.
  5. (1996). A replication-defective human adenovirus recombinant serves as a highly efficacious vaccine carrier.
  6. (2006). Adenoviral keratoconjunctivitis in a tertiary care eye clinic,
  7. (2008). Adenovirus 5 and 35 vectors expressing Plasmodium falciparum circumsporozoite surface protein elicit potent antigenspecific cellular IFN-gamma and antibody responses in mice.
  8. (2010). Adenovirus 5-fiber 35 chimeric vector mediates efficient apical correction of the cystic fibrosis transmembrane conductance regulator defect in cystic fibrosis primary airway epithelia.
  9. (2008). Adenovirus E3/19K promotes evasion of NK cell recognition by intracellular sequestration of the NKG2D ligands major histocompatibility complex class I chain-related proteins A
  10. (2002). Adenovirus fibre disrupts CAR-mediated intercellular adhesion allowing virus escape.
  11. (1953). Adenovirus serotype 5 E1A sensitizes tumor cells to NKG2D-dependent NK cell lysis and tumor rejection.
  12. (2007). Adenovirus type 11 binding alters the conformation of its receptor CD46.
  13. (1997). Adenovirus type 5 fiber knob binds to MHC class I alpha2 domain at the surface of human epithelial and B lymphoblastoid cells.
  14. (2004). Adenovirus type 5 pseudotyped with adenovirus type 37 fibre uses sialic acid as a cellular receptor.
  15. (2002). Adenovirus type37 binds to cell surface sialic acid through a chargedependent interaction. Virology 302, 33–43
  16. (1999). Adenoviruses activate human dendritic cells without polarisation toward a T helper type 1 inducing subset.
  17. (1994). Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis.
  18. (1985). An adenovirus type 2 glycoprotein blocks cell surface expression of human histocompatibility class I antigens.
  19. (2000). An efficient recombination system for chromosome engineering in Escherichia coli PNAS.
  20. (2005). Avian influenza and sialic acid receptors: more than meets the eye? Lancet Infect.
  21. (1999). Basolateral localization of fibre receptors limits adenovirus infection from the apical surface of airway epithelia.
  22. (2003). Binding of adenovirus capsid to dipalmitoylphosphatidylcholine provides a novel pathway for virus entry.
  23. (1967). Biochemical studies on Adenovirus multiplication. XIII. Plaquing efficiencies of purified human adenoviruses.
  24. (2007). Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state.
  25. (2001). by Adenovirus Proteins.
  26. (2002). Characterization of E3/49K, a novel, highly glycosylated E3 protein of the epidemic keratoconjunctivitis-causing adenovirus type 19a.
  27. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
  28. (2009). Coagulation factors IX and X enhance binding and infection of adenovirus types 5 and 31 in human epithelial cells.
  29. (2003). Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene.
  30. (2007). Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups
  31. (2007). Comparison of adenoviruses from species B, C, E, and F after intravenous delivery.
  32. (2010). Conserved amino acids within the adenovirus 2 E3/19K protein differentially affect downregulation of MHC class I and MICA/B
  33. (2001). Construction and characterization of recombinant porcine adenovirus serotype 5 expressing the transmissible gastroenteritis virus spike gene.
  34. (1985). Construction of non-defective adenovirus type 5 bearing a 2.8-kilobase hepatitis B virus DNA near the right end of its genome.
  35. (1997). Contrasting effects of TGF-β and TNF-α on the development of dendritic cells from progenitors in mouse bone marrow.
  36. (2004). Crystal structure of species D adenovirus fibre knobs and their sialic acid binding sites.
  37. (1994). Crystal structure of the receptor-binding domain of adenovirus type 5 fiber protein at 1.7 A resolution.
  38. (1999). Cutting edge: Adenovirus E19 has two mechanisms for affecting class I MHC expression.
  39. (2009). Defining the role of CD46, CD80 and CD86 in mediating adenovirus type 3 fiber interactions with host cells.
  40. (2005). Dendritic cells as therapeutic vaccines against
  41. (2008). Dendritic cells: a critical player in cancer therapy.
  42. (2000). Design and construction of an experimental HIV-1 vaccine for a year-2000 clinical trial in
  43. (2000). Development of a preventive vaccine for Ebola virus infection in primates.
  44. (1989). Downregulation by cytokines and bacterial products.
  45. (2005). Downregulation of natural killer cellactivating ligand CD155 by human cytomegalovirus UL141.
  46. (1995). E3 transcription unit of adenovirus.
  47. (1987). E3/19K" protein of adenovirus type 2 inhibits lysis of cytolytic T lymphocytes by blocking cell surface-expression of histocompatibility class I antigens.
  48. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study). A double-blind, randomised, placebo-controlled, test-of-concept trial.
  49. (1996). Efficient generation of recombinant adenovirus vectors by homologous recombination in Escherichia coli.
  50. (2002). Engineered expression of the coxsackie B and adenovirus receptor (CAR) in human dendritic cells enhances recombinant adenovirusmediated gene transfer.
  51. (2005). Enhanced immunogenicity using an alphavirus replicon DNA vaccine against human immunodeficiency virus type 1.
  52. (1992). Evidence for intracellular down-regulation of the epidermal growth factor (EGF) receptor during adenovirus infection by an EGF-independent mechanism.
  53. (2004). Four viruses, two bacteria, and one receptor: membrane cofactor protein (CD46) as pathogens' magnet.
  54. (1986). Further characterization of 41 isolates of adenovirus types 19/37 by serum neutralization and DNA restriction enzyme analysis.
  55. (1989). Gangliosides influence experimental influenza virus infection in mice.
  56. (2002). Gene-modified dendritic cells for immunotherapy against cancer.
  57. (2006). Generation of a novel replication-incompetent adenoviral vector derived from human adenovirus type 49: manufacture on PER.C6 cells, tropism and immunogenicity
  58. (2006). Generation of an adenoviral vaccine vector based on simian adenovirus 21.
  59. (2009). Harnessing human dendritic cell subsets to design novel vaccines.
  60. (2009). Heterologous prime/boost immunizations of rhesus monkeys using chimpanzee adenovirus vectors.
  61. (2002). Hexon gene switch strategy for the generation of chimeric recombinant adenovirus.
  62. (2002). HIV-1 vaccine-induced immunity in the test-of-concept Step Study: A case-cohort analysis.
  63. (2009). Human adenovirus type 19: genomic and bioinformatics analysis of a keratoconjunctivitis isolate. Virus Res.
  64. (1992). Identification and characterization of membrane cofactor protein of human spermatozoa.
  65. (1999). Identification of a cell protein (FIP-3) as a modulator of NFkappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis.
  66. (1994). Identification of a conserved receptor-binding site on the fibre proteins of CARrecognizing adenoviridae.
  67. (2003). Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein.
  68. (1998). Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankarabased multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice.
  69. (2000). Immunomodulatory Functions Encoded by the E3 Transcription Unit of Adenoviruses.
  70. (2006). Improved gene delivery to intestinal mucosa by adenoviral vectors bearing subgroup B and D fibres.
  71. (1973). In vitro cultivation of human tumors: Establishment of cell lines derived from a series of solid tumors.
  72. (2006). Inhibition of TNF receptor 1 internalisation by adenovirus 14.7K as a novel immnune escape mechanism.
  73. (1997). Innate immune mechanisms dominate elimination of adenoviral vectors following in vivo administration.
  74. (1997). Interaction of an adenovirus 14.7-kilodalton protein inhibitor of tumor necrosis factor alpha cytolysis with a new member of the GTPase superfamily of signal transducers.
  75. (1998). Interaction of an adenovirus E3 14.7-kilodalton protein with a novel tumor necrosis factor alpha-inducible cellular protein containing leucine zipper domains.
  76. (2006). Intradermal delivery of adenoviral type-35 vectors leads to high efficiency transduction of mature, CD8+ T cell-stimulating skin-emigrated Dendritic cells.
  77. (1991). Isoforms differ in protection against the classical pathway of complement.
  78. (1978). Isolation of deletion and substitution mutants of adenovirus type 5.
  79. (2007). Loss of TLR2, TLR4, and TLR5 on Langerhans cells abolishes bacterial recognition.
  80. (2004). Membrane cofactor protein is a receptor for adenoviruses associated with epidemic keratoconjunctivitis.
  81. (2004). Modifying adenoviral vectors for use as gene-based cancer vaccines.
  82. (2007). Multivalent sialic acid conjugates inhibit adenovirus type 37 from binding to and infecting human corneal epithelial cells.
  83. (2007). Myeloid and plasmacytoid dendritic cells are susceptible to recombinant adenovirus vectors and stimulate polyfunctional memory T cell responses.
  84. (2007). New Adenovirus Species Found in a Patient Presenting with Gastroenteritis.
  85. (1998). New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses.
  86. (1997). Novel adenovirus vaccine vectors based on the enteric-tropic serotype 41.
  87. (2004). Novel replication-incompetent vector derived from adenovirus type 11 (Ad11) for vaccination and gene therapy: low seroprevalence and non-crossreactivity with Ad5.
  88. (2005). Overexpression of GD1a ganglioside sensitizes motor nerve terminals to anti-GD1a antibody-mediated injury in a model of acute motor axonal neuropathy.
  89. (1999). Ovine adenovirus vectors overcome preexisting humoral immunity against human adenoviruses in vivo.
  90. (1998). Pathogenesis of pneumovirus infections in mice: detection ofpneumonia virus of mice and human respiratory syncytial virus mRNA in lungs of infected mice by in situ hybridization.
  91. (1999). Plasmacytoid monocytes migrate to inflamed lymph nodes and produce large amounts of type I interferon.
  92. (2010). Prime-boost immunization with adenoviral and modified vaccinia virus Ankara vectors enhances the durability and polyfunctionality of protective malaria CD8+ T-cell responses.
  93. (2000). Proapoptotic functions of cytotoxic lymphocyte granule constituents in vitro and in vivo.
  94. (2010). Progress and prospects: immune responses to viral vectors. Gene Ther.
  95. (2001). Receptor for the group B coxsackieviruses and adenoviruses:
  96. (2002). Recombinant adenovirus encoding the HA gene from swine H3N2 influenza virus partially protects mice from challenge with heterologous virus: A/HK/1/68 (H3N2).
  97. (1954). Recovery of new agent from patients with acute respiratory illness.
  98. (2009). Recpetor usage of a newly emergent adenovirus type 14. Virology 387,
  99. (1998). Regulated RNA processing and RNA transport during adenovirus infection. Seminars in Virology 8,
  100. (2001). Replication-defective vector based on a chimpanzee adenovirus.
  101. (1994). Replicationincompetent adenoviruses as vectors for protective immunization against measles virus infection.
  102. (2006). Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy--a review.
  103. (2000). Respiratory syncytial virus infection in adults.
  104. (1980). Restriction endonucleases in identification of a genome type of adenovirus 19 associated with keratoconjunctivitis.
  105. (2005). Simple and highly efficient BAC recombineering using galK selection. Nucleic Acids Res.
  106. (1981). Specific gangliosides function as host cell receptors for Sendai virus.
  107. (2001). Structural analysis of a fiber-pseudotyped adenovirus with ocular tropism suggests differential modes of cell receptor interactions.
  108. (2007). Structural variations in species B adenovirus fibres impact CD46 association.
  109. (2002). Subversion of host defense mechanisms by adenoviruses.
  110. (1991). The 10,400- and 14,500-Dalton proteins encoded by region E3 of Adenovirus form a complex and function together to down-regulate the epidermal growth factor receptor.
  111. (2001). The coxsackie and adenovirus receptor is a transmembrane component of the tight junction.
  112. (1998). The coxsackie-adenovirus receptor protein can function as a cellular attachment protein from adenovirus serotypes from subgroups
  113. (1995). The CTL’s kiss of death.
  114. (1992). The evolution of mouse and human complement C3-binding proteins: divergence of form but conservation of function.
  115. (2007). The influence of blood on in vivo adenovirus bio-distribution and transduction.
  116. (2002). The novel early region 3 protein E3/49K is specifically expressed by adenoviruses of subgenus D: implications for epidemic keratoconjunctivitis and adenovirus evolution.
  117. (2005). The pneumonia virus of mice infection model for severe respiratory syncytial virus infection: identifying novel targets for therapeutic intervention.
  118. (1984). The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL 2 production reflects events occurring at a pre-translational level.
  119. (1977). The Seattle Virus Watch. VII. Observations of adenovirus infections.
  120. (2006). Transposon-assisted cloning and traceless mutagenesis of Adenoviruses: Development of a novel vector based on species D.
  121. (2009). Update on structure and function.
  122. (2001). Vascular cell adhesion molecule-1 augments adenovirus-mediated gene transfer.
  123. (2001). Viral vectors for dendritic cell based immunotherapy. Trends in Immunol.

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