1887

Abstract

Adenoviral vectors based on adenovirus type 35 (rAd35) have the advantage of low natural vector immunity and induce strong, insert-specific T- and B-cell responses, making them prime-candidate vaccine carriers. However, severe vector-genome instability of E1-deleted rAd35 vectors was observed, hampering universal use. The instability of E1-deleted rAd35 vector proved to be caused by low pIX expression induced by removal of the pIX promoter, which was located in the E1B region of B-group viruses. Reinsertion of a minimal pIX promoter resulted in stable vectors able to harbour large DNA inserts (>5 kb). In addition, it is shown that replacement of the E4-Orf6 region of Ad35 by the E4-Orf6 region of Ad5 resulted in successful propagation of an E1-deleted rAd35 vector on existing E1-complementing cell lines, such as PER.C6 cells. The ability to produce these carriers on PER.C6 contributes significantly to the scale of manufacturing of rAd35-based vaccines. Next, a stable rAd35 vaccine was generated carrying antigens Ag85A, Ag85B and TB10.4. The antigens were fused directly, resulting in expression of a single polyprotein. This vaccine induced dose-dependent CD4 and CD8 T-cell responses against multiple antigens in mice. It is concluded that the described improvements to the rAd35 vector contribute significantly to the further development of rAd35 carriers for mass-vaccination programmes for diseases such as tuberculosis, AIDS and malaria.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81956-0
2006-08-01
2021-07-24
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/8/2135.html?itemId=/content/journal/jgv/10.1099/vir.0.81956-0&mimeType=html&fmt=ahah

References

  1. Arribillaga L., de Cerio A. L. D., Sarobe P. & 9 other authors 2002; Vaccination with an adenoviral vector encoding hepatitis C virus (HCV) NS3 protein protects against infection with HCV-recombinant vaccinia virus. Vaccine 21:202–210 [CrossRef]
    [Google Scholar]
  2. Babiss L. E., Vales L. D. 1991; Promoter of the adenovirus polypeptide IX gene: similarity to E1B and inactivation by substitution of the simian virus 40 TATA element. J Virol 65:598–605
    [Google Scholar]
  3. Barouch D. H., Nabel G. J. 2005; Adenovirus vector-based vaccines for human immunodeficiency virus type 1. Hum Gene Ther 16:149–156 [CrossRef]
    [Google Scholar]
  4. Barouch D. H., McKay P. F., Sumida S. M. & 8 other authors 2003; Plasmid chemokines and colony-stimulating factors enhance the immunogenicity of DNA priming-viral vector boosting human immunodeficiency virus type 1 vaccines. J Virol 77:8729–8735 [CrossRef]
    [Google Scholar]
  5. Barouch D. H., Pau M. G., Custers J. H. H. V. & 15 other authors 2004; Immunogenicity of recombinant adenovirus serotype 35 vaccine in the presence of pre-existing anti-Ad5 immunity. J Immunol 172:6290–6297 [CrossRef]
    [Google Scholar]
  6. Bett A. J., Prevec L., Graham F. L. 1993; Packaging capacity and stability of human adenovirus type 5 vectors. J Virol 67:5911–5921
    [Google Scholar]
  7. Caravokyri C., Leppard K. N. 1995; Constitutive episomal expression of polypeptide IX (pIX) in a 293-based cell line complements the deficiency of pIX mutant adenovirus type 5. J Virol 69:6627–6633
    [Google Scholar]
  8. Casimiro D. R., Chen L., Fu T.-M. & 36 other authors 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. J Virol 77:6305–6313 [CrossRef]
    [Google Scholar]
  9. Cohen C. J., Xiang Z. Q., Gao G.-P., Ertl H. C. J., Wilson J. M., Bergelson J. M. 2002; Chimpanzee adenovirus CV-68 adapted as a gene delivery vector interacts with the coxsackievirus and adenovirus receptor. J Gen Virol 83:151–155
    [Google Scholar]
  10. Colby W. W., Shenk T. 1981; Adenovirus type 5 virions can be assembled in vivo in the absence of detectable polypeptide IX. J Virol 39:977–980
    [Google Scholar]
  11. Fallaux F. J., Kranenburg O., Cramer S. J., Houweling A., Van Ormondt H., Hoeben R. C., Van Der Eb A. J. 1996; Characterization of 911: a new helper cell line for the titration and propagation of early region 1-deleted adenoviral vectors. Hum Gene Ther 7:215–222 [CrossRef]
    [Google Scholar]
  12. Fallaux F. J., Bout A., van der Velde I. & 9 other authors 1998; New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses. Hum Gene Ther 9:1909–1917 [CrossRef]
    [Google Scholar]
  13. Ghosh-Choudhury G., Haj-Ahmad Y., Graham F. L. 1987; Protein IX, a minor component of the human adenovirus capsid, is essential for the packaging of full length genomes. EMBO J 6:1733–1739
    [Google Scholar]
  14. Holterman L., Vogels R., van der Vlugt R. & 15 other authors 2004; Novel replication-incompetent vector derived from adenovirus type 11 (Ad11) for vaccination and gene therapy: low seroprevalence and non-cross-reactivity with Ad5. J Virol 78:13207–13215 [CrossRef]
    [Google Scholar]
  15. Jaiswal S., Khanna N., Swaminathan S. 2003; Replication-defective adenoviral vaccine vector for the induction of immune responses to dengue virus type 2. J Virol 77:12907–12913 [CrossRef]
    [Google Scholar]
  16. Jones D., Kroos N., Anema R. & 12 other authors 2003; High-level expression of recombinant IgG in the human cell line PER.C6. Biotechnol Prog 19:163–168 [CrossRef]
    [Google Scholar]
  17. Kostense S., Koudstaal W., Sprangers M. & 8 other authors 2004; Adenovirus types 5 and 35 seroprevalence in AIDS risk groups supports type 35 as a vaccine vector. AIDS 18:1213–1216 [CrossRef]
    [Google Scholar]
  18. Lemckert A. A. C., Sumida S. M., Holterman L. & 10 other authors 2005; Immunogenicity of heterologous prime-boost regimens involving recombinant adenovirus serotype 11 (Ad11) and Ad35 vaccine vectors in the presence of anti-Ad5 immunity. J Virol 79:9694–9701 [CrossRef]
    [Google Scholar]
  19. Liu R.-Y., Wu L.-Z., Huang B.-J. & 9 other authors 2005; Adenoviral expression of a truncated S1 subunit of SARS-CoV spike protein results in specific humoral immune responses against SARS-CoV in rats. Virus Res 112:24–31 [CrossRef]
    [Google Scholar]
  20. Lutz P., Rosa-Calatrava M., Kedinger C. 1997; The product of the adenovirus intermediate gene IX is a transcriptional activator. J Virol 71:5102–5109
    [Google Scholar]
  21. Maizel J. V. Jr, White D. O., Scharff M. D. 1968; The polypeptides of adenovirus. I. Evidence for multiple protein components in the virion and a comparison of types 2, 7A, and 12. Virology 36:115–125 [CrossRef]
    [Google Scholar]
  22. Ophorst O. J. A. E., Radošević K., Havenga M. J. E., Pau M. G., Holterman L., Berkhout B., Goudsmit J., Tsuji M. 2006; Immunogenicity and protection of a recombinant human adenovirus serotype 35-based malaria vaccine against Plasmodium yoelii in mice. Infect Immun 74:313–320 [CrossRef]
    [Google Scholar]
  23. Phillpotts R. J., O'Brien L., Appleton R. E., Carr S., Bennett A. 2005; Intranasal immunisation with defective adenovirus serotype 5 expressing the Venezuelan equine encephalitis virus E2 glycoprotein protects against airborne challenge with virulent virus. Vaccine 23:1615–1623 [CrossRef]
    [Google Scholar]
  24. Pinto A. R., Fitzgerald J. C., Giles-Davis W., Gao G. P., Wilson J. M., Ertl H. C. J. 2003; Induction of CD8+ T cells to an HIV-1 antigen through a prime boost regimen with heterologous E1-deleted adenoviral vaccine carriers. J Immunol 171:6774–6779 [CrossRef]
    [Google Scholar]
  25. Pinto A. R., Fitzgerald J. C., Gao G. P., Wilson J. M., Ertl H. C. J. 2004; Induction of CD8+ T cells to an HIV-1 antigen upon oral immunization of mice with a simian E1-deleted adenoviral vector. Vaccine 22:697–703 [CrossRef]
    [Google Scholar]
  26. Rosa-Calatrava M., Grave L., Puvion-Dutilleul F., Chatton B., Kedinger C. 2001; Functional analysis of adenovirus protein IX identifies domains involved in capsid stability, transcriptional activity, and nuclear reorganization. J Virol 75:7131–7141 [CrossRef]
    [Google Scholar]
  27. Rosa-Calatrava M., Puvion-Dutilleul F., Lutz P., Dreyer D., de Thé H., Chatton B., Kedinger C. 2003; Adenovirus protein IX sequesters host-cell promyelocytic leukaemia protein and contributes to efficient viral proliferation. EMBO Rep 4:969–975 [CrossRef]
    [Google Scholar]
  28. Rubenwolf S., Schütt H., Nevels M., Wolf H., Dobner T. 1997; Structural analysis of the adenovirus type 5 E1B 55-kilodalton–E4orf6 protein complex. J Virol 71:1115–1123
    [Google Scholar]
  29. Sargent K. L., Meulenbroek R. A., Parks R. J. 2004; Activation of adenoviral gene expression by protein IX is not required for efficient virus replication. J Virol 78:5032–5037 [CrossRef]
    [Google Scholar]
  30. Seaman M. S., Xu L., Beaudry K. & 11 other authors 2005; Multiclade human immunodeficiency virus type 1 envelope immunogens elicit broad cellular and humoral immunity in rhesus monkeys. J Virol 79:2956–2963 [CrossRef]
    [Google Scholar]
  31. Shabram P. W., Giroux D. D., Goudreau A. M. & 7 other authors 1997; Analytical anion-exchange HPLC of recombinant type-5 adenoviral particles. Hum Gene Ther 8:453–465 [CrossRef]
    [Google Scholar]
  32. Shanley J. D., Wu C. A. 2003; Mucosal immunization with a replication-deficient adenovirus vector expressing murine cytomegalovirus glycoprotein B induces mucosal and systemic immunity. Vaccine 21:2632–2642 [CrossRef]
    [Google Scholar]
  33. Shiver J. W., Emini E. A. 2004; Recent advances in the development of HIV-1 vaccines using replication-incompetent adenovirus vectors. Annu Rev Med 55:355–372 [CrossRef]
    [Google Scholar]
  34. Shiver J. W., Fu T.-M., Chen L. 49 other authors 2002; Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature 415:331–335 [CrossRef]
    [Google Scholar]
  35. Sullivan N. J., Geisbert T. W., Geisbert J. B., Xu L., Yang Z.-Y., Roederer M., Koup R. A., Jarhling P. B., Nabel G. J. 2003; Accelerated vaccination for Ebola virus haemorrhagic fever in non-human primates. Nature 424:681–684 [CrossRef]
    [Google Scholar]
  36. Sumida S. M., Truitt D. M., Lemckert A. A. C. & 15 other authors 2005; Neutralizing antibodies to adenovirus serotype 5 vaccine vectors are directed primarily against the adenovirus hexon protein. J Immunol 174:7179–7185 [CrossRef]
    [Google Scholar]
  37. Tan Y., Hackett N. R., Boyer J. L., Crystal R. G. 2003; Protective immunity evoked against anthrax lethal toxin after a single intramuscular administration of an adenovirus-based vaccine encoding humanized protective antigen. Hum Gene Ther 14:1673–1682 [CrossRef]
    [Google Scholar]
  38. Vogels R., Zuijdgeest D., van Rijnsoever R. & 20 other authors 2003; Replication-deficient human adenovirus type 35 vectors for gene transfer and vaccination: efficient human cell infection and bypass of preexisting adenovirus immunity. J Virol 77:8263–8271 [CrossRef]
    [Google Scholar]
  39. Weigel S., Dobbelstein M. 2000; The nuclear export signal within the E4orf6 protein of adenovirus type 5 supports virus replication and cytoplasmic accumulation of viral mRNA. J Virol 74:764–772 [CrossRef]
    [Google Scholar]
  40. Wu L., Kong W.-P., Nabel G. J. 2005; Enhanced breadth of CD4 T-cell immunity by DNA prime and adenovirus boost immunization to human immunodeficiency virus Env and Gag immunogens. J Virol 79:8024–8031 [CrossRef]
    [Google Scholar]
  41. Xiang Z., Gao G., Reyes-Sandoval A., Cohen C. J., Li Y., Bergelson J. M., Wilson J. M., Ertl H. C. J. 2002; Novel, chimpanzee serotype 68-based adenoviral vaccine carrier for induction of antibodies to a transgene product. J Virol 76:2667–2675 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81956-0
Loading
/content/journal/jgv/10.1099/vir.0.81956-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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