1887

Abstract

The vectorization of rare human adenovirus (HAdV) types will widen our knowledge of this family and their interaction with cells, tissues and organs. In this study we focus on HAdV-56, a member of human Ad species D, and create ease-of-use cloning systems to generate recombinant HAdV-56 vectors carrying foreign genes. We present transduction profiles for HAdV-56 in direct comparison to the most commonly used HAdV-5-based vector. characterizations demonstrate that when it is delivered intravenously (i.v.) HAdV-56 mainly targets the spleen and, to a lesser extent, the lungs, whilst largely bypassing liver transduction in mice. HAdV-56 triggered robust inflammatory and cellular immune responses, with higher induction of IFNγ, TNFα, IL5, IL6, IP10, MCP1 and MIG1 compared to HAdV-5 following i.v. administration. We also investigated its potential as a vaccine vector candidate by performing prime immunizations in mice with HAdV-56 encoding luciferase (HAdV-56-Luc). Direct comparisons were made to HAdV-26, a highly potent human vaccine vector currently in phase II clinical trials. HAdV-56-Luc induced luciferase ‘antigen’-specific IFNγ-producing cells and anti-HAdV-56 neutralizing antibodies in Balb/c mice, demonstrating a near identical profile to that of HAdV-26. Taken together, the data presented provides further insight into human Ad receptor/co-receptor usage, and the first report on HAdV-56 vectors and their potential for gene therapy and vaccine applications.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000978
2018-01-01
2019-12-14
Loading full text...

Full text loading...

/deliver/fulltext/jgv/99/1/135.html?itemId=/content/journal/jgv/10.1099/jgv.0.000978&mimeType=html&fmt=ahah

References

  1. Sasaki T, Tazawa H, Hasei J, Osaki S, Kunisada T et al. A simple detection system for adenovirus receptor expression using a telomerase-specific replication-competent adenovirus. Gene Ther 2013;20:112–118 [CrossRef][PubMed]
    [Google Scholar]
  2. Zhang W, Fu J, Liu J, Wang H, Schiwon M et al. An engineered virus library as a resource for the spectrum-wide exploration of virus and vector diversity. Cell Rep 2017;19:1698–1709 [CrossRef][PubMed]
    [Google Scholar]
  3. Belousova N, Mikheeva G, Xiong C, Stagg LJ, Gagea M et al. Native and engineered tropism of vectors derived from a rare species D adenovirus serotype 43. Oncotarget 2016;7:5341453429 [CrossRef][PubMed]
    [Google Scholar]
  4. Weaver EA, Barry MA. Low seroprevalent species D adenovirus vectors as influenza vaccines. PLoS One 2013;8:e73313 [CrossRef][PubMed]
    [Google Scholar]
  5. Kahl CA, Bonnell J, Hiriyanna S, Fultz M, Nyberg-Hoffman C et al. Potent immune responses and in vitro pro-inflammatory cytokine suppression by a novel adenovirus vaccine vector based on rare human serotype 28. Vaccine 2010;28:5691–5702 [CrossRef][PubMed]
    [Google Scholar]
  6. Ruzsics Z, Wagner M, Osterlehner A, Cook J, Koszinowski U et al. Transposon-assisted cloning and traceless mutagenesis of adenoviruses: development of a novel vector based on species D. J Virol 2006;80:8100–8113 [CrossRef][PubMed]
    [Google Scholar]
  7. Alonso-Padilla J, Papp T, Kaján GL, Benkő M, Havenga M et al. Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs. Mol Ther 2016;24:6–16 [CrossRef][PubMed]
    [Google Scholar]
  8. Chen H, Xiang ZQ, Li Y, Kurupati RK, Jia B et al. Adenovirus-based vaccines: comparison of vectors from three species of adenoviridae. J Virol 2010;84:10522–10532 [CrossRef][PubMed]
    [Google Scholar]
  9. Nemerow GR, Stewart PL. Insights into adenovirus uncoating from interactions with integrins and mediators of host immunity. Viruses 2016;8:337 [CrossRef][PubMed]
    [Google Scholar]
  10. Nilsson EC, Storm RJ, Bauer J, Johansson SM, Lookene A et al. The GD1a glycan is a cellular receptor for adenoviruses causing epidemic keratoconjunctivitis. Nat Med 2011;17:105–109 [CrossRef][PubMed]
    [Google Scholar]
  11. Arnberg N, Kidd AH, Edlund K, Olfat F, Wadell G. Initial interactions of subgenus D adenoviruses with A549 cellular receptors: sialic acid versus alpha(v) integrins. J Virol 2000;74:7691–7693 [CrossRef][PubMed]
    [Google Scholar]
  12. Burmeister WP, Guilligay D, Cusack S, Wadell G, Arnberg N. Crystal structure of species D adenovirus fiber knobs and their sialic acid binding sites. J Virol 2004;78:7727–7736 [CrossRef][PubMed]
    [Google Scholar]
  13. Abbink P, Lemckert AA, Ewald BA, Lynch DM, Denholtz M et al. Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D. J Virol 2007;81:4654–4663 [CrossRef][PubMed]
    [Google Scholar]
  14. Robinson CM, Singh G, Henquell C, Walsh MP, Peigue-Lafeuille H et al. Computational analysis and identification of an emergent human adenovirus pathogen implicated in a respiratory fatality. Virology 2011;409:141–147 [CrossRef][PubMed]
    [Google Scholar]
  15. Havenga M, Vogels R, Zuijdgeest D, Radosevic K, Mueller S et al. Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells. J Gen Virol 2006;87:2135–2143 [CrossRef][PubMed]
    [Google Scholar]
  16. Nevels M, Spruss T, Wolf H, Dobner T. The adenovirus E4orf6 protein contributes to malignant transformation by antagonizing E1A-induced accumulation of the tumor suppressor protein p53. Oncogene 1999;18:9–17 [CrossRef][PubMed]
    [Google Scholar]
  17. Enomoto M, Okafuji T, Okafuji T, Chikahira M, Konagaya M et al. Isolation of an intertypic recombinant human adenovirus (candidate type 56) from the pharyngeal swab of a patient with pharyngoconjunctival fever. Jpn J Infect Dis 2012;65:457–459 [CrossRef][PubMed]
    [Google Scholar]
  18. Huang G, Yao W, Yu W, Mao L, Sun H et al. Outbreak of epidemic keratoconjunctivitis caused by human adenovirus type 56, China, 2012. PLoS One 2014;9:e110781 [CrossRef][PubMed]
    [Google Scholar]
  19. Hiroi S, Furubayashi K, Kawahata T, Morikawa S, Kase T. A case of urethritis caused by human adenovirus type 56. Jpn J Infect Dis 2012;65:273–274 [CrossRef][PubMed]
    [Google Scholar]
  20. Singh G, Zhou X, Lee JY, Yousuf MA, Ramke M et al. Recombination of the epsilon determinant and corneal tropism: Human adenovirus species D types 15, 29, 56, and 69. Virology 2015;485:452–459 [CrossRef][PubMed]
    [Google Scholar]
  21. Zhang XP, Puzon-Mclaughlin W, Irie A, Kovach N, Prokopishyn NL et al. α3β1 1 adhesion to laminin-5 and invasin: critical and differential role of integrin residues clustered at the boundary between α 3 N-terminal repeats 2 and 3. Biochemistry 1999;38:14424–14431 [CrossRef][PubMed]
    [Google Scholar]
  22. Eto K, Huet C, Tarui T, Kupriyanov S, Liu HZ et al. Functional classification of ADAMs based on a conserved motif for binding to integrin α9β1: implications for sperm-egg binding and other cell interactions. J Biol Chem 2002;277:17804–17810 [CrossRef][PubMed]
    [Google Scholar]
  23. Lu M, Munger JS, Steadele M, Busald C, Tellier M et al. Integrin α8β1 mediates adhesion to LAP-TGFβ1. Journal of Cell Science 2002;115:4641–4648[Crossref]
    [Google Scholar]
  24. Eto K, Puzon-Mclaughlin W, Sheppard D, Sehara-Fujisawa A, Zhang XP et al. RGD-independent binding of integrin α9β1 to the ADAM-12 and -15 disintegrin domains mediates cell-cell interaction. J Biol Chem 2000;275:34922–34930 [CrossRef][PubMed]
    [Google Scholar]
  25. Mould AP, Askari JA, Humphries MJ. Molecular basis of ligand recognition by integrin α5β1. I. Specificity of ligand binding is determined by amino acid sequences in the second and third NH2-terminal repeats of the α subunit. J Biol Chem 2000;275:20324–20336 [CrossRef][PubMed]
    [Google Scholar]
  26. Isobe T, Hisaoka T, Shimizu A, Okuno M, Aimoto S et al. Propolypeptide of von Willebrand factor is a novel ligand for very late antigen-4 integrin. J Biol Chem 1997;272:8447–8453 [CrossRef][PubMed]
    [Google Scholar]
  27. Irie A, Kamata T, Puzon-Mclaughlin W, Takada Y. Critical amino acid residues for ligand binding are clustered in a predicted beta-turn of the third N-terminal repeat in the integrin alpha 4 and alpha 5 subunits. Embo J 1995;14:5550–5556[PubMed]
    [Google Scholar]
  28. Schreiner CL, Bauer JS, Danilov YN, Hussein S, Sczekan MM et al. Isolation and characterization of Chinese hamster ovary cell variants deficient in the expression of fibronectin receptor. J Cell Biol 1989;109:3157–3167[PubMed][Crossref]
    [Google Scholar]
  29. Flintoff-Dye NL, Welser J, Rooney J, Scowen P, Tamowski S et al. Role for the α7β1 integrin in vascular development and integrity. Dev Dyn 2005;234:11–21 [CrossRef][PubMed]
    [Google Scholar]
  30. Yao CC, Breuss J, Pytela R, Kramer RH. Functional expression of the alpha 7 integrin receptor in differentiated smooth muscle cells. J Cell Sci 1997;110:1477–1487[PubMed]
    [Google Scholar]
  31. Waddington SN, Mcvey JH, Bhella D, Parker AL, Barker K et al. Adenovirus serotype 5 hexon mediates liver gene transfer. Cell 2008;132:397–409 [CrossRef][PubMed]
    [Google Scholar]
  32. Qiu Q, Xu Z, Tian J, Moitra R, Gunti S et al. Impact of natural IgM concentration on gene therapy with adenovirus type 5 vectors. J Virol 2015;89:3412–3416 [CrossRef][PubMed]
    [Google Scholar]
  33. Shayakhmetov DM, Gaggar A, Ni S, Li ZY, Lieber A. Adenovirus binding to blood factors results in liver cell infection and hepatotoxicity. J Virol 2005;79:7478–7491 [CrossRef][PubMed]
    [Google Scholar]
  34. Parker AL, Waddington SN, Nicol CG, Shayakhmetov DM, Buckley SM et al. Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes. Blood 2006;108:2554–2561 [CrossRef][PubMed]
    [Google Scholar]
  35. Coughlan L, Bradshaw AC, Parker AL, Robinson H, White K et al. Ad5:Ad48 hexon hypervariable region substitutions lead to toxicity and increased inflammatory responses following intravenous delivery. Mol Ther 2012;20:2268–2281 [CrossRef][PubMed]
    [Google Scholar]
  36. Bradshaw AC, Coughlan L, Miller AM, Alba R, van Rooijen N et al. Biodistribution and inflammatory profiles of novel penton and hexon double-mutant serotype 5 adenoviruses. J Control Release 2012;164:394–402 [CrossRef][PubMed]
    [Google Scholar]
  37. Milligan ID, Gibani MM, Sewell R, Clutterbuck EA, Campbell D et al. Safety and immunogenicity of novel adenovirus type 26- and modified vaccinia ankara-vectored ebola vaccines: a randomized clinical trial. JAMA 2016;315:1610–1623 [CrossRef][PubMed]
    [Google Scholar]
  38. Baden LR, Karita E, Mutua G, Bekker LG, Gray G et al. Assessment of the safety and immunogenicity of 2 novel vaccine platforms for HIV-1 prevention: a randomized trial. Ann Intern Med 2016;164:313–322 [CrossRef][PubMed]
    [Google Scholar]
  39. Arnberg N. Adenovirus receptors: implications for targeting of viral vectors. Trends Pharmacol Sci 2012;33:442–448 [CrossRef][PubMed]
    [Google Scholar]
  40. Storm RJ, Persson BD, Skalman LN, Frängsmyr L, Lindström M et al. Human adenovirus type 37 uses αVβ1 and α3β1 integrins for infection of human corneal cells. J Virol 2017;91: [CrossRef][PubMed]
    [Google Scholar]
  41. Dakin RS, Parker AL, Delles C, Nicklin SA, Baker AH. Efficient transduction of primary vascular cells by the rare adenovirus serotype 49 vector. Hum Gene Ther 2015;26:312–319 [CrossRef][PubMed]
    [Google Scholar]
  42. Thirion C, Lochmüller H, Ruzsics Z, Boelhauve M, König C et al. Adenovirus vectors based on human adenovirus type 19a have high potential for human muscle-directed gene therapy. Hum Gene Ther 2006;17:193–205 [CrossRef][PubMed]
    [Google Scholar]
  43. Ledgerwood JE, DeZure AD, Stanley DA, Coates EE, Novik L et al. Chimpanzee adenovirus vector ebola vaccine. N Engl J Med 2017;376:928–938 [CrossRef][PubMed]
    [Google Scholar]
  44. Antrobus RD, Coughlan L, Berthoud TK, Dicks MD, Hill AV et al. Clinical assessment of a novel recombinant simian adenovirus ChAdOx1 as a vectored vaccine expressing conserved Influenza A antigens. Mol Ther 2014;22:668–674 [CrossRef][PubMed]
    [Google Scholar]
  45. Barouch DH, Picker LJ. Novel vaccine vectors for HIV-1. Nat Rev Microbiol 2014;12:765–771 [CrossRef]
    [Google Scholar]
  46. Baden LR, Walsh SR, Seaman MS, Tucker RP, Krause KH et al. First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001). J Infect Dis 2013;207:240–247 [CrossRef][PubMed]
    [Google Scholar]
  47. Gibson DG, Young L, Chuang RY, Venter JC, Hutchison CA et al. Enzymatic assembly of DNA molecules up to several hundred kilobases. Nat Methods 2009;6:343–345 [CrossRef][PubMed]
    [Google Scholar]
  48. Nicklin SA, Baker AH. Simple methods for preparing recombinant adenoviruses for high-efficiency transduction of vascular cells. Methods Mol Med 1999;30:271–283 [CrossRef][PubMed]
    [Google Scholar]
  49. Johansson SM, Nilsson EC, Elofsson M, Ahlskog N, Kihlberg J et al. Multivalent sialic acid conjugates inhibit adenovirus type 37 from binding to and infecting human corneal epithelial cells. Antiviral Res 2007;73:92–100 [CrossRef][PubMed]
    [Google Scholar]
  50. Sprangers MC, Lakhai W, Koudstaal W, Verhoeven M, Koel BF et al. Quantifying adenovirus-neutralizing antibodies by luciferase transgene detection: addressing preexisting immunity to vaccine and gene therapy vectors. J Clin Microbiol 2003;41:5046–5052 [CrossRef][PubMed]
    [Google Scholar]
  51. Ma J, Duffy MR, Deng L, Dakin RS, Uil T et al. Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo. PLoS Pathog 2015;11:e1004673 [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000978
Loading
/content/journal/jgv/10.1099/jgv.0.000978
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error