Seoul virus (SEOV) is one of the four hantaviruses known to cause haemorrhagic fever with renal syndrome. The medium genome segment encodes the Gn/Gc glycoproteins of SEOV, which form the major structural part of the virus envelope. Gc and/or Gn are the candidate antigens of hantavirus for induction of a highly immunogenic response for hantavirus vaccine. In this study, the immune response induced by a replication-competent recombinant canine adenovirus type 2 expressing the Gc protein of SEOV was evaluated in BALB/c mice. Sera from immunized mice contained neutralizing antibodies that could specifically recognize SEOV and neutralize its infectivity . Moreover, the recombinant virus induced complete protection against an intensive infectious challenge with ∼1000 50 % infective doses for SEOV strain CC-2. Protective-level neutralizing antibodies were maintained for at least 20 weeks. This recombinant virus is therefore a potential alternative to the inactivated vaccine.


Article metrics loading...

Loading full text...

Full text loading...



  1. Araki, K., Yoshimatsu, K., Ogino, M., Ebihara, H., Lundkvist, A., Kariwa, H., Takashima, I. & Arikawa, J.(2001). Truncated hantavirus nucleocapsid proteins for serotyping Hantaan, Seoul, and Dobrava hantavirus infections. J Clin Microbiol 39, 2397–2404.[CrossRef] [Google Scholar]
  2. Asada, H., Balachandra, K., Tamura, M., Kondo, K. & Yamanishi, K.(1989). Cross-reactive immunity among different serotypes of virus causing haemorrhagic fever with renal syndrome. J Gen Virol 70, 819–825.[CrossRef] [Google Scholar]
  3. 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]
  4. Bharadwaj, M., Lyons, C. R., Wortman, I. A. & Hjelle, B.(1999). Intramuscular inoculation of Sin Nombre hantavirus cDNAs induces cellular and humoral immune responses in BALB/c mice. Vaccine 17, 2836–2843.[CrossRef] [Google Scholar]
  5. Bounous, D. I., Campagnoli, R. P. & Brown, J.(1992). Comparison of MTT colorimetric assay and tritiated thymidine uptake for lymphocyte proliferation assays using chicken splenocytes. Avian Dis 36, 1022–1027.[CrossRef] [Google Scholar]
  6. Christensen, J., Alexandersen, S., Bloch, B., Aasted, B. & Uttenthal, A.(1994). Production of mink enteritis parvovirus empty capsids by expression in a baculovirus vector system: a recombinant vaccine for mink enteritis parvovirus in mink. J Gen Virol 75, 149–155.[CrossRef] [Google Scholar]
  7. Elliott, R. M.(1990). Molecular biology of Bunyaviridae. J Gen Virol 71, 501–522.[CrossRef] [Google Scholar]
  8. Fan, Q. S., Xia, X. Z., Gao, Y. W. & Huang, G.(1982). Attenuation SY strain of CAV-2 strain. Chin J Vet 35, 7–9 (in Chinese). [Google Scholar]
  9. Ferreira, T. B., Alves, P. M., Aunins, J. G. & Carrondo, M. J. T.(2005). Use of adenoviral vectors as veterinary vaccines. Gene Ther 12, S73–S83.[CrossRef] [Google Scholar]
  10. Geldmacher, A., Skrastina, D., Petrovskis, I., Borisova, G., Berriman, J. A., Roseman, A. M., Crowther, R. A., Fischer, J., Musema, S. & other authors(2004). An amino-terminal segment of hantavirus nucleocapsid protein presented on hepatitis B virus core particles induces a strong and highly cross-reactive antibody response in mice. Virology 323, 108–119.[CrossRef] [Google Scholar]
  11. Hong, W., Xiao, S., Zhou, R., Fang, L., He, Q., Wu, B., Zhou, F. & Chen, H.(2002). Protection induced by intramuscular immunization with DNA vaccines of pseudorabies in mice, rabbits and piglets. Vaccine 20, 1205–1214.[CrossRef] [Google Scholar]
  12. Hooper, J. W., Kamrud, K. I., Elgh, F., Custer, D. & Schmaljohn, C. S.(1999). DNA vaccine with hantavirus M segment elicits neutralizing antibodies and protects against Seoul virus infection. Virology 255, 269–278.[CrossRef] [Google Scholar]
  13. Hooper, J. W., Custer, D. M., Thompson, E. & Schmaljohn, C. S.(2001). DNA vaccination with the Hantaan virus M gene protects hamsters against three of four HFRS hantaviruses and elicits a high-titer neutralizing antibody response in rhesus monkeys. J Virol 75, 8469–8477.[CrossRef] [Google Scholar]
  14. Hu, R., Zhang, S., Fooks, A. R., Yuan, H., Liu, Y., Li, H., Tu, C., Xia, X. & Xiao, Y.(2006). Prevention of rabies virus infection in dogs by a recombinant canine adenovirus type-2 encoding the rabies virus glycoprotein. Microbes Infect 8, 1090–1097.[CrossRef] [Google Scholar]
  15. Hu, R. L., Liu, Y., Zhang, S. F., Zhang, F. & Fooks, A. R.(2007). Experimental immunization of cats with a recombinant rabies–canine adenovirus vaccine elicits a long-lasting neutralizing antibody response against rabies. Vaccine 25, 5301–5307.[CrossRef] [Google Scholar]
  16. Jonsson, C. B. & Schmaljohn, C. S.(2001). Replication of hantaviruses. Curr Top Microbiol Immunol 256, 15–32. [Google Scholar]
  17. Kariwa, H., Yoshimatsu, K. & Arikawa, J.(2007). Hantavirus infection in East Asia. Comp Immunol Microbiol Infect Dis 30, 341–356.[CrossRef] [Google Scholar]
  18. Langeveld, J. P., Casal, J. I., Cortes, E., van de Wetering, G., Boshuizen, R. S., Schaaper, W. M., Dalsgaard, K. & Meloen, R. H.(1994). Effective induction of neutralizing antibodies with the amino terminus of VP2 of canine parvovirus as a synthetic peptide. Vaccine 12, 1473–1480.[CrossRef] [Google Scholar]
  19. Li, J., Faber, M., Papaneri, A., Faber, M. L., McGettigan, J. P., Schnell, M. J. & Dietzschold, B.(2006). A single immunization with a recombinant canine adenovirus expressing the rabies virus G protein confers protective immunity against rabies in mice. Virology 356, 147–154.[CrossRef] [Google Scholar]
  20. Morrison, M. D., Reid, D., Onions, D., Spibey, N. & Nicolson, L.(2002). Generation of E3-deleted canine adenoviruses expressing canine parvovirus capsid by homologous recombination in bacteria. Virology 293, 26–30.[CrossRef] [Google Scholar]
  21. Randrianarison-Jewtoukoff, V. & Perricaudet, M.(1995). Recombinant adenoviruses as vaccines. Biologicals 23, 145–157.[CrossRef] [Google Scholar]
  22. Reed, L. J. & Münch, R. H.(1938). A simple method of estimating fifty percent endpoints. Am J Hyg 27, 493–497. [Google Scholar]
  23. Reid, S. M., Ferris, N. P., Hutchings, G. H., De Clercq, K., Newman, B. J., Knowl, N. J. & Samuel, A. R.(2001). Diagnosis of foot-and-mouth disease by RT-PCR: use of phylogenetic data to evaluate primers for the typing of viral RNA in clinical samples. Arch Virol 146, 2421–2434.[CrossRef] [Google Scholar]
  24. Schmaljohn, C. & Hjelle, B.(1997). Hantaviruses: a global disease problem. Emerg Infect Dis 3, 95–104.[CrossRef] [Google Scholar]
  25. Schmaljohn, C. S. & Le Duc, J. W.(1998).Bunyaviridae. In Topley and Wilson’s Microbiology and Microbial Infections, 9th edn, pp. 601–628. Edited by L. H. Collier, A. Balows & M. Sussman. London: M. Arnold.
  26. Schmaljohn, C. S., Chu, Y. K., Schmaljohn, A. L. & Dalrymple, J. M.(1990). Antigenic subunits of Hantaan virus expressed by baculovirus and vaccinia virus recombinants. J Virol 64, 3162–3170. [Google Scholar]
  27. Schmidt, N. J., Lennette, E. H. & King, C. J.(1966). Neutralizing, hemagglutination-inhibiting and group complement-fixing antibody responses in human adenovirus infections. J Immunol 97, 64–74. [Google Scholar]
  28. Shenk, T.(1996). Adenoviruses. In Fields Virology, 3rd edn, pp. 2111–2148. Philadelphia, PA: Lippincott-Raven.
  29. Tham, K. M., Horner, G. W. & Hunter, R.(1998). Isolation and identification of canine adenovirus type-2 from the upper respiratory tract of a dog. N Z Vet J 46, 102–105.[CrossRef] [Google Scholar]
  30. Wichmann, D., Grone, H. J., Frese, M., Pavlovic, J., Anheier, B., Haller, O., Klenk, H. D. & Feldmann, H.(2002). Hantaan virus infection causes an acute neurological disease that is fatal in adult laboratory mice. J Virol 76, 8890–8899.[CrossRef] [Google Scholar]
  31. Xia, X. Z., Fang, Q. S. & Huang, G.(2000). Isolation and identification of a canine adenovirus avirulent strain. Chin J Vet Med 34, 1–4 (in Chinese). [Google Scholar]
  32. Xiao, S., Chen, H., Fang, L., Liu, C., Zhang, H., Jiang, Y. & Hong, W.(2004). Comparison of immune responses and protective efficacy of suicidal DNA vaccine and conventional DNA vaccine encoding glycoprotein C of pseudorabies virus in mice. Vaccine 22, 345–351.[CrossRef] [Google Scholar]
  33. Xu, Z. Z., Hyatt, A., Boyle, D. B. & Both, G. W.(1997). Construction of ovine adenovirus recombinants by gene insertion or deletion of related terminal region sequences. Virology 230, 62–71.[CrossRef] [Google Scholar]
  34. Yamamoto, T.(1966). Some physical and growth characteristics of a canine adenovirus isolated from dogs with laryngotracheitis. Can J Microbiol 12, 303–311.[CrossRef] [Google Scholar]
  35. Yuan, Z., Zhang, X., Zhang, S., Xu, H., Wang, X. & Hu, R.(2008). Study on high-level expression of hantavirus S gene in prokaryocyte. Chin J Vector Bio & Control 19, 237–240 (in Chinese). [Google Scholar]
  36. Yuan, Z. G., Li, X. M., Mahmmod, Y. S., Wang, X. H., Xu, H. J. & Zhang, X. X.(2009). A single immunization with a recombinant canine adenovirus type 2 expressing the Seoul virus Gn glycoprotein confers protective immunity against Seoul virus in mice. Vaccine 27, 5247–5251.[CrossRef] [Google Scholar]
  37. Zakhartchouk, A. N., Reddy, P. S., Baxi, M., Baca-Estrada, M. E., Mehtali, M., Babiuk, L. A. & Tikoo, S. K.(1998). Construction and characterization of E3-deleted bovine adenovirus type 3 expressing full length and truncated form of bovine herpesvirus type 1 glycoprotein gD. Virology 250, 220–229.[CrossRef] [Google Scholar]
  38. Zhang, S. F., Hu, R. L., Niu, J. Q. & Xia, X. Z.(2002). Cloning and identification of the full length infectious genome of canine adenovirus type-2. Chin J Vet Sci 22, 533–535 (in Chinese). [Google Scholar]
  39. Zhang, S., Liu, Y., Fooks, A. R., Zhang, F. & Hu, R.(2008). Oral vaccination of dogs (Canis familiaris) with baits containing the recombinant rabies–canine adenovirus type-2 vaccine confers long-lasting immunity against rabies. Vaccine 26, 345–350.[CrossRef] [Google Scholar]

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