1887

Abstract

During the development of human adenovirus 35-derived replication-incompetent (rAd35) vaccine vectors for prevention of infectious diseases, we detected mutations in the terminal 8 nt of the inverted terminal repeats (ITRs) of rAd35. The switch from the plasmid-encoded sequence 5′-CATCATCA-3′ to the alternative sequence 5′-CTATCTAT-3′ in the ITRs was found to be a general propagation phenomenon, as shown for several vectors carrying different transgenes or being derived from different adenovirus serotypes. In each tested case, the plasmid-encoded ITR sequence changed to exactly the same alternative ITR sequence, 5′-CTATCTAT-3′. The outgrowth of this alternative ITR version should result from a growth advantage conferred by the alternative ITR sequence. Indeed, replication kinetics studies of rAd35 harbouring either the original or alternative ITR sequence confirmed an increase in replication speed for rAd35 vectors with the alternative ITR sequence. These findings can be applied to generate recombinant adenoviral vectors harbouring the alternative ITR sequence, which will facilitate the generation of genetically homogeneous seed virus batches. Moreover, vector production may be accelerated by taking advantage of the observed improved replication kinetics associated with the alternative ITR sequence.

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2014-07-01
2024-03-29
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References

  1. Abbink P., Lemckert A. A., Ewald B. A., Lynch D. M., Denholtz M., Smits S., Holterman L., Damen I., Vogels R. other authors 2007; Comparative seroprevalence and immunogenicity of six rare serotype recombinant adenovirus vaccine vectors from subgroups B and D. J Virol 81:4654–4663 [View Article][PubMed]
    [Google Scholar]
  2. Aleström P., Stenlund A., Li P., Pettersson U. 1982; A common sequence in the inverted terminal repetitions of human and avian adenoviruses. Gene 18:193–197 [View Article][PubMed]
    [Google Scholar]
  3. 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. other authors 2011; International seroepidemiology of adenovirus serotypes 5, 26, 35, and 48 in pediatric and adult populations. Vaccine 29:5203–5209 [View Article][PubMed]
    [Google Scholar]
  4. 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. 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]
  5. Bernstein J. A., Porter J. M., Challberg M. D. 1986; Template requirements for in vivo replication of adenovirus DNA. Mol Cell Biol 6:2115–2124[PubMed]
    [Google Scholar]
  6. Buchbinder S. P., Mehrotra D. V., Duerr A., Fitzgerald D. W., Mogg R., Li D., Gilbert P. B., Lama J. R., Marmor M. other authors 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 372:1881–1893 [View Article][PubMed]
    [Google Scholar]
  7. Challberg M. D., Rawlins D. R. 1984; Template requirements for the initiation of adenovirus DNA replication. Proc Natl Acad Sci U S A 81:100–104 [View Article][PubMed]
    [Google Scholar]
  8. Dán A., Elö P., Harrach B., Zádori Z., Benkö M. 2001; Four new inverted terminal repeat sequences from bovine adenoviruses reveal striking differences in the length and content of the ITRs. Virus Genes 22:175–179 [View Article][PubMed]
    [Google Scholar]
  9. de Jong R. N., van der Vliet P. C., Brenkman A. B. 2003; Adenovirus DNA replication: protein priming, jumping back and the role of the DNA binding protein DBP. Curr Top Microbiol Immunol 272:187–211[PubMed]
    [Google Scholar]
  10. Dekker J., Kanellopoulos P. N., Loonstra A. K., van Oosterhout J. A., Leonard K., Tucker P. A., van der Vliet P. C. 1997; Multimerization of the adenovirus DNA-binding protein is the driving force for ATP-independent DNA unwinding during strand displacement synthesis. EMBO J 16:1455–1463 [View Article][PubMed]
    [Google Scholar]
  11. Desiderio S. V., Kelly T. J. Jr 1981; Structure of the linkage between adenovirus DNA and the 55,000 molecular weight terminal protein. J Mol Biol 145:319–337 [View Article][PubMed]
    [Google Scholar]
  12. Enomoto T., Lichy J. H., Ikeda J. E., Hurwitz J. 1981; Adenovirus DNA replication in vitro: purification of the terminal protein in a functional form. Proc Natl Acad Sci U S A 78:6779–6783 [View Article][PubMed]
    [Google Scholar]
  13. Fallaux F. J., Bout A., van der Velde I., van den Wollenberg D. J., Hehir K. M., Keegan J., Auger C., Cramer S. J., van Ormondt H. 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 [View Article][PubMed]
    [Google Scholar]
  14. Gao W., Robbins P. D., Gambotto A. 2003; Human adenovirus type 35: nucleotide sequence and vector development. Gene Ther 10:1941–1949 [View Article][PubMed]
    [Google Scholar]
  15. Guggenheimer R. A., Stillman B. W., Nagata K., Tamanoi F., Hurwitz J. 1984; DNA sequences required for the in vitro replication of adenovirus DNA. Proc Natl Acad Sci U S A 81:3069–3073 [View Article][PubMed]
    [Google Scholar]
  16. Harris M. P., Hay R. T. 1988; DNA sequences required for the initiation of adenovirus type 4 DNA replication in vitro. J Mol Biol 201:57–67 [View Article][PubMed]
    [Google Scholar]
  17. Havenga M., Vogels R., Zuijdgeest D., Radosevic K., Mueller S., Sieuwerts M., Weichold F., Damen I., Kaspers J. other authors 2006; Novel replication-incompetent adenoviral B-group vectors: high vector stability and yield in PER.C6 cells. J Gen Virol 87:2135–2143 [View Article][PubMed]
    [Google Scholar]
  18. Hay R. T. 1985; The origin of adenovirus DNA replication: minimal DNA sequence requirement in vivo. EMBO J 4:421–426[PubMed]
    [Google Scholar]
  19. Houng H. S., Clavio S., Graham K., Kuschner R., Sun W., Russell K. L., Binn L. N. 2006; Emergence of a new human adenovirus type 4 (Ad4) genotype: identification of a novel inverted terminal repeated (ITR) sequence from majority of Ad4 isolates from US military recruits. J Clin Virol 35:381–387 [View Article][PubMed]
    [Google Scholar]
  20. Jacobs S. C., Davison A. J., Carr S., Bennett A. M., Phillpotts R., Wilkinson G. W. 2004; Characterization and manipulation of the human adenovirus 4 genome. J Gen Virol 85:3361–3366 [View Article][PubMed]
    [Google Scholar]
  21. King A. J., van der Vliet P. C. 1994; A precursor terminal protein-trinucleotide intermediate during initiation of adenovirus DNA replication: regeneration of molecular ends in vitro by a jumping back mechanism. EMBO J 13:5786–5792[PubMed]
    [Google Scholar]
  22. King A. J., Teertstra W. R., van der Vliet P. C., Blanco L., Salas M. 1997a; Processive proofreading by the adenovirus DNA polymerase. Association with the priming protein reduces exonucleolytic degradation. Nucleic Acids Res 25:1745–1752 [View Article][PubMed]
    [Google Scholar]
  23. King A. J., Teertstra W. R., van der Vliet P. C. 1997b; Dissociation of the protein primer and DNA polymerase after initiation of adenovirus DNA replication. J Biol Chem 272:24617–24623 [View Article][PubMed]
    [Google Scholar]
  24. Liu H., Naismith J. H., Hay R. T. 2003; Adenovirus DNA replication. Curr Top Microbiol Immunol 272:131–164[PubMed]
    [Google Scholar]
  25. McCoy K., Tatsis N., Korioth-Schmitz B., Lasaro M. O., Hensley S. E., Lin S. W., Li Y., Giles-Davis W., Cun A. other authors 2007; Effect of preexisting immunity to adenovirus human serotype 5 antigens on the immune responses of nonhuman primates to vaccine regimens based on human- or chimpanzee-derived adenovirus vectors. J Virol 81:6594–6604 [View Article][PubMed]
    [Google Scholar]
  26. Purkayastha A., Su J., McGraw J., Ditty S. E., Hadfield T. L., Seto J., Russell K. L., Tibbetts C., Seto D. 2005; Genomic and bioinformatics analyses of HAdV-4vac and HAdV-7vac, two human adenovirus (HAdV) strains that constituted original prophylaxis against HAdV-related acute respiratory disease, a reemerging epidemic disease. J Clin Microbiol 43:3083–3094 [View Article][PubMed]
    [Google Scholar]
  27. Rademaker H. J., Fallaux F. J., Van den Wollenberg D. J., De Jong R. N., Van der Vliet P. C., Hoeben R. C. 2006; Relaxed template specificity in fowl adenovirus 1 DNA replication initiation. J Gen Virol 87:553–562 [View Article][PubMed]
    [Google Scholar]
  28. Radosevic K., Wieland C. W., Rodriguez A., Weverling G. J., Mintardjo R., Gillissen G., Vogels R., Skeiky Y. A., Hone D. M. other authors 2007; Protective immune responses to a recombinant adenovirus type 35 tuberculosis vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of gamma interferon. Infect Immun 75:4105–4115 [View Article][PubMed]
    [Google Scholar]
  29. Schwarz E., Reinke C., Yamamoto N., zur Hausen H. 1982; Terminal rearrangements in the genome of adenovirus type 12 mutants adapted to growth in two human tumor cell lines. Virology 116:284–296 [View Article][PubMed]
    [Google Scholar]
  30. Shinagawa M., Padmanabhan R. 1980; Comparative sequence analysis of the inverted terminal repetitions from different adenoviruses. Proc Natl Acad Sci U S A 77:3831–3835 [View Article][PubMed]
    [Google Scholar]
  31. Shinagawa M., Ishiyama T., Padmanabhan R., Fujinaga K., Kamada M., Sato G. 1983; Comparative sequence analysis of the inverted terminal repetition in the genomes of animal and avian adenoviruses. Virology 125:491–495 [View Article][PubMed]
    [Google Scholar]
  32. Shinagawa M., Iida Y., Matsuda A., Tsukiyama T., Sato G. 1987; Phylogenetic relationships between adenoviruses as inferred from nucleotide sequences of inverted terminal repeats. Gene 55:85–93 [View Article][PubMed]
    [Google Scholar]
  33. Smart J. E., Stillman B. W. 1982; Adenovirus terminal protein precursor. Partial amino acid sequence and the site of covalent linkage to virus DNA. J Biol Chem 257:13499–13506[PubMed]
    [Google Scholar]
  34. Tokunaga O., Shinagawa M., Padmanabhan R. 1982; Physical mapping of the genome and sequence analysis at the inverted terminal repetition of adenovirus type 4 DNA. Gene 18:329–334 [View Article][PubMed]
    [Google Scholar]
  35. van Bergen B. G., van der Ley P. A., van Driel W., van Mansfeld A. D., van der Vliet P. C. 1983; Replication of origin containing adenovirus DNA fragments that do not carry the terminal protein. Nucleic Acids Res 11:1975–1989 [View Article][PubMed]
    [Google Scholar]
  36. Vogels R., Zuijdgeest D., van Rijnsoever R., Hartkoorn E., Damen I., de Béthune M. P., Kostense S., Penders G., Helmus N. 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 [View Article][PubMed]
    [Google Scholar]
  37. Wang K., Pearson G. D. 1985; Adenovirus sequences required for replication in vivo. Nucleic Acids Res 13:5173–5187 [View Article][PubMed]
    [Google Scholar]
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