1887

Abstract

Although potential neutralization epitopes on the fiber knob of adenovirus (AdV) serotype 2 (Ad2) and Ad5 have been revealed, few studies have been carried out to identify neutralization epitopes on the knob from a broader panel of AdV serotypes. In this study, based on sequence and structural analysis of knobs from Ad1, Ad2, Ad5 and Ad6 (all from species C), several trimeric chimeric knob proteins were expressed in to identify the locations of neutralization epitopes on the knobs by analysing their reactivity with mouse and rabbit polyclonal sera raised against AdVs and human sera with natural AdV infection. The dominant neutralization epitopes were located mainly in the N-terminal part of knobs from Ad1, Ad2 and Ad5, but they seemed to be located in the C-terminal part of the Ad6 knob, with some individual differences in rabbit and human populations. Our study adds to our understanding of humoral immune responses to AdVs and will facilitate the construction of more desirable capsid-modified recombinant Ad5 vectors.

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2016-04-01
2024-03-29
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References

  1. Arnberg N. 2012; Adenovirus receptors: implications for targeting of viral vectors. Trends Pharmacol Sci 33:442–448 [View Article][PubMed]
    [Google Scholar]
  2. Bradley R. R., Lynch D. M., Iampietro M. J., Borducchi E. N., Barouch D. H. 2012; Adenovirus serotype 5 neutralizing antibodies target both hexon and fiber following vaccination and natural infection. J Virol 86:625–629 [View Article][PubMed]
    [Google Scholar]
  3. Cheng C., Gall J. G., Nason M., King C. R., Koup R. A., Roederer M., McElrath M. J., Morgan C. A., Churchyard G., other authors. 2010; Differential specificity and immunogenicity of adenovirus type 5 neutralizing antibodies elicited by natural infection or immunization. J Virol 84:630–638 [View Article][PubMed]
    [Google Scholar]
  4. Coughlan L., Alba R., Parker A. L., Bradshaw A. C., McNeish I. A., Nicklin S. A., Baker A. H. 2010; Tropism-modification strategies for targeted gene delivery using adenoviral vectors. Viruses 2:2290–2355 [View Article][PubMed]
    [Google Scholar]
  5. Fender P., Kidd A. H., Brebant R., Oberg M., Drouet E., Chroboczek J. 1995; Antigenic sites on the receptor-binding domain of human adenovirus type 2 fiber. Virology 214:110–117 [View Article][PubMed]
    [Google Scholar]
  6. Gahéry-Ségard H., Farace F., Godfrin D., Gaston J., Lengagne R., Tursz T., Boulanger P., Guillet J. G. 1998; Immune response to recombinant capsid proteins of adenovirus in humans: antifiber and anti-penton base antibodies have a synergistic effect on neutralizing activity. J Virol 72:2388–2397[PubMed]
    [Google Scholar]
  7. Kirby I., Davison E., Beavil A. J., Soh C. P., Wickham T. J., Roelvink P. W., Kovesdi I., Sutton B. J., Santis G. 2000; Identification of contact residues and definition of the CAR-binding site of adenovirus type 5 fiber protein. J Virol 74:2804–2813 [View Article][PubMed]
    [Google Scholar]
  8. Liebermann H., Mentel R., Bauer U., Pring-Akerblom P., Dölling R., Modrow S., Seidel W. 1998; Receptor binding sites and antigenic epitopes on the fiber knob of human adenovirus serotype 3. J Virol 72:9121–9130[PubMed]
    [Google Scholar]
  9. Liebermann H., Lotz K., Mentel R., Bauer U., Seidel W. 2001; Mapping of linear epitopes on fibre knob of human adenovirus serotype 5. Virus Res 73:145–151 [View Article][PubMed]
    [Google Scholar]
  10. Liebermann H., Lotz K., Seidel W. 2002; Mapping of epitopes on the fiber knobs of human adenovirus serotypes 8 and 15. Intervirology 45:59–66 [View Article][PubMed]
    [Google Scholar]
  11. Majhen D., Calderon H., Chandra N., Fajardo C. A., Rajan A., Alemany R., Custers J. 2014; Adenovirus-based vaccines for fighting infectious diseases and cancer: progress in the field. Hum Gene Ther 25:301–317 [View Article][PubMed]
    [Google Scholar]
  12. 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]
  13. Ng P., Parks R. J., Cummings D. T., Evelegh C. M., Graham F. L. 2000; An enhanced system for construction of adenoviral vectors by the two-plasmid rescue method. Hum Gene Ther 11:693–699 [View Article][PubMed]
    [Google Scholar]
  14. Roelvink P. W., Mi Lee G., Einfeld D. A., Kovesdi I., Wickham T. J. 1999; Identification of a conserved receptor-binding site on the fiber proteins of CAR-recognizing Adenoviridae . Science 286:1568–1571 [View Article][PubMed]
    [Google Scholar]
  15. Seiradake E., Lortat-Jacob H., Billet O., Kremer E. J., Cusack S. 2006; Structural and mutational analysis of human Ad37 and canine adenovirus 2 fiber heads in complex with the D1 domain of coxsackie and adenovirus receptor. J Biol Chem 281:33704–33716 [View Article][PubMed]
    [Google Scholar]
  16. Sharma A., Tandon M., Ahi Y. S., Bangari D. S., Vemulapalli R., Mittal S. K. 2010; Evaluation of cross-reactive cell-mediated immune responses among human, bovine and porcine adenoviruses. Gene Ther 17:634–642 [View Article][PubMed]
    [Google Scholar]
  17. van Raaij M. J., Louis N., Chroboczek J., Cusack S. 1999a; Structure of the human adenovirus serotype 2 fiber head domain at 1.5 Å resolution. Virology 262:333–343 [View Article][PubMed]
    [Google Scholar]
  18. van Raaij M. J., Mitraki A., Lavigne G., Cusack S. 1999b; A triple β-spiral in the adenovirus fibre shaft reveals a new structural motif for a fibrous protein. Nature 401:935–938 [View Article][PubMed]
    [Google Scholar]
  19. Xia D., Henry L. J., Gerard R. D., Deisenhofer J. 1994; Crystal structure of the receptor-binding domain of adenovirus type 5 fiber protein at 1.7 Å resolution. Structure 2:1259–1270 [View Article][PubMed]
    [Google Scholar]
  20. Yeh H. Y., Pieniazek N., Pieniazek D., Gelderblom H., Luftig R. B. 1994; Human adenovirus type 41 contains two fibers. Virus Res 33:179–198 [View Article][PubMed]
    [Google Scholar]
  21. Yu B., Dong J., Wang C., Zhan Y., Zhang H., Wu J., Kong W., Yu X. 2013; Characteristics of neutralizing antibodies to adenovirus capsid proteins in human and animal sera. Virology 437:118–123 [View Article][PubMed]
    [Google Scholar]
  22. Yu B., Dong J., Wang C., Wang Z., Gao L., Zhang H., Wu J., Kong W., Yu X. 2014; Trimeric knob protein specifically distinguishes neutralizing antibodies to different human adenovirus species: potential application for adenovirus seroepidemiology. J Gen Virol 95:1564–1573 [View Article][PubMed]
    [Google Scholar]
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