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Comparison of the immunogenicity of two inactivated recombinant rabies viruses overexpressing the glycoprotein

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Abstract

Two recombinant rabies viruses overexpressing their glycoprotein (G) were compared in this study, with the overexpressed G inserted between P and M genes (named LBNSE-PM-G), and between the G and L genes (named LBNSE-GL-G), respectively. LBNSE-PM-G produced more G protein and induced stronger apoptosis than LBNSE-GL-G in infected cells, while the amount of virion-incorporated G in LBNSE-PM-G was less than in LBNSE-GL-G. Mice immunized with inactivated LBNSE-PM-G produced lower titers of virus-neutralizing antibody, and this recombinant conferred worse protection than LBNSE-GL-G. Our results suggest that over expressed G gene inserted between G and L, but not between P and M, enhanced the immunogenicity when used as an inactivated rabies vaccine.

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References

  1. Hampson K, Coudeville L, Lembo T, Sambo M, Kieffer A, Attlan M, Barrat J, Blanton JD, Briggs DJ, Cleaveland S, Costa P, Freuling CM, Hiby E, Knopf L, Leanes F, Meslin FX, Metlin A, Miranda ME, Muller T, Nel LH, Recuenco S, Rupprecht CE, Schumacher C, Taylor L, Vigilato MA, Zinsstag J, Dushoff J, Alliance Global, for Rabies Control Partners for Rabies Prevention (2015) Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis 9(4):e0003709. doi:10.1371/journal.pntd.0003709

    Article  PubMed  PubMed Central  Google Scholar 

  2. Hu RL, Fooks AR, Zhang SF, Liu Y, Zhang F (2008) Inferior rabies vaccine quality and low immunization coverage in dogs (Canis familiaris) in China. Epidemiol Infect 136(11):1556–1563. doi:10.1017/S0950268807000131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Fitzpatrick MC, Hampson K, Cleaveland S, Mzimbiri I, Lankester F, Lembo T, Meyers LA, Paltiel AD, Galvani AP (2014) Cost-effectiveness of canine vaccination to prevent human rabies in rural Tanzania. Ann Intern Med 160(2):91–100. doi:10.7326/M13-0542

    Article  PubMed  PubMed Central  Google Scholar 

  4. Schnell MJ, McGettigan JP, Wirblich C, Papaneri A (2010) The cell biology of rabies virus: using stealth to reach the brain. Nat Rev Microbiol 8(1):51–61. doi:10.1038/nrmicro2260

    CAS  PubMed  Google Scholar 

  5. Liu X, Yang Y, Sun Z, Chen J, Ai J, Dun C, Fu ZF, Niu X, Guo X (2014) A recombinant rabies virus encoding two copies of the glycoprotein gene confers protection in dogs against a virulent challenge. PLoS One 9(2):e87105. doi:10.1371/journal.pone.0087105

    Article  PubMed  PubMed Central  Google Scholar 

  6. Plotkin SA (2005) Vaccines: past, present and future. Nat Med 11(4 Suppl):S5–11. doi:10.1038/nm1209

    Article  CAS  PubMed  Google Scholar 

  7. Faber M, Pulmanausahakul R, Hodawadekar SS, Spitsin S, McGettigan JP, Schnell MJ, Dietzschold B (2002) Overexpression of the rabies virus glycoprotein results in enhancement of apoptosis and antiviral immune response. J Virol 76(7):3374–3381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schutsky K, Curtis D, Bongiorno EK, Barkhouse DA, Kean RB, Dietzschold B, Hooper DC, Faber M (2013) Intramuscular inoculation of mice with the live-attenuated recombinant rabies virus TriGAS results in a transient infection of the draining lymph nodes and a robust, long-lasting protective immune response against rabies. J Virol 87(3):1834–1841. doi:10.1128/JVI.02589-12

    Article  CAS  PubMed  Google Scholar 

  9. Tao L, Ge J, Wang X, Wen Z, Zhai H, Hua T, Zhao B, Kong D, Yang C, Bu Z (2011) Generation of a recombinant rabies Flury LEP virus carrying an additional G gene creates an improved seed virus for inactivated vaccine production. Virol J 8:454. doi:10.1186/1743-422X-8-454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhao L, Toriumi H, Wang H, Kuang Y, Guo X, Morimoto K, Fu ZF (2010) Expression of MIP-1alpha (CCL3) by a recombinant rabies virus enhances its immunogenicity by inducing innate immunity and recruiting dendritic cells and B cells. J Virol 84(18):9642–9648. doi:10.1128/JVI.00326-10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Pulmanausahakul R, Faber M, Morimoto K, Spitsin S, Weihe E, Hooper DC, Schnell MJ, Dietzschold B (2001) Overexpression of cytochrome C by a recombinant rabies virus attenuates pathogenicity and enhances antiviral immunity. J Virol 75(22):10800–10807. doi:10.1128/JVI.75.22.10800-10807.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wen Y, Wang H, Wu H, Yang F, Tripp RA, Hogan RJ, Fu ZF (2011) Rabies virus expressing dendritic cell-activating molecules enhances the innate and adaptive immune response to vaccination. J Virol 85(4):1634–1644. doi:10.1128/JVI.01552-10

    Article  CAS  PubMed  Google Scholar 

  13. Albertini AA, Ruigrok RW, Blondel D (2011) Rabies virus transcription and replication. Adv Virus Res 79:1–22. doi:10.1016/B978-0-12-387040-7.00001-9

    Article  CAS  PubMed  Google Scholar 

  14. Rasalingam P, Rossiter JP, Mebatsion T, Jackson AC (2005) Comparative pathogenesis of the SAD-L16 strain of rabies virus and a mutant modifying the dynein light chain binding site of the rabies virus phosphoprotein in young mice. Virus Res 111(1):55–60. doi:10.1016/j.virusres.2005.03.010

    Article  CAS  PubMed  Google Scholar 

  15. Conzelmann KK, Cox JH, Schneider LG, Thiel HJ (1990) Molecular cloning and complete nucleotide sequence of the attenuated rabies virus SAD B19. Virology 175(2):485–499

    Article  CAS  PubMed  Google Scholar 

  16. Schnell MJ, Mebatsion T, Conzelmann KK (1994) Infectious rabies viruses from cloned cDNA. EMBO J 13(18):4195–4203

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Tian D, Luo Z, Zhou M, Li M, Yu L, Wang C, Yuan J, Li F, Tian B, Sui B, Chen H, Fu ZF, Zhao L (2015) Critical role of K1685 and K1829 in the large protein of rabies virus in viral pathogenicity and immune evasion. J Virol 90(1):232–244. doi:10.1128/JVI.02050-15

    Article  PubMed  Google Scholar 

  18. Hosokawa-Muto J, Ito N, Yamada K, Shimizu K, Sugiyama M, Minamoto N (2006) Characterization of recombinant rabies virus carrying double glycoprotein genes. Microbiol Immunol 50(3):187–196

    Article  CAS  PubMed  Google Scholar 

  19. Wu X, Rupprecht CE (2008) Glycoprotein gene relocation in rabies virus. Virus Res 131(1):95–99. doi:10.1016/j.virusres.2007.07.018

    Article  CAS  PubMed  Google Scholar 

  20. Xue XH, Zheng XX, Wang HL, Ma JZ, Li L, Gai WW, Wang TC, Yang ST, Xia XZ (2014) An inactivated recombinant rabies CVS-11 virus expressing two copies of the glycoprotein elicits a higher level of neutralizing antibodies and provides better protection in mice. Virus Genes 48(3):411–420. doi:10.1007/s11262-014-1049-9

    Article  CAS  PubMed  Google Scholar 

  21. Sarmento L, Li XQ, Howerth E, Jackson AC, Fu ZF (2005) Glycoprotein-mediated induction of apoptosis limits the spread of attenuated rabies viruses in the central nervous system of mice. J Neurovirol 11(6):571–581. doi:10.1080/13550280500385310

    Article  CAS  PubMed  Google Scholar 

  22. Yan X, Mohankumar PS, Dietzschold B, Schnell MJ, Fu ZF (2002) The rabies virus glycoprotein determines the distribution of different rabies virus strains in the brain. J Neurovirol 8(4):345–352. doi:10.1080/13550280290100707

    Article  CAS  PubMed  Google Scholar 

  23. Finke S, Mueller-Waldeck R, Conzelmann KK (2003) Rabies virus matrix protein regulates the balance of virus transcription and replication. J Gen Virol 84(Pt 6):1613–1621. doi:10.1099/vir.0.19128-0

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported partially by the National Natural Science Foundation of China (31372419) and Huazhong Agricultural University Scientific & Technological Self-Innovation Foundation (2012RC009 and 2014JQ003) for LZ; National Natural Science Foundation of China (31330078) and Ministry of Agriculture of the People’s Republic of China (Special Fund for Agro-Scientific Research in the Public Interest, 201303042) for ZFF.

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Correspondence to Lijun Tang or Ling Zhao.

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The authors declare no conflict of interest.

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All procedures performed in studies involving animals were in accordance with the ethical standards approved by the Scientific Ethics Committee of Huazhong Agricultural University, China (HZAUMO-2015-016).

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M. T. Navid and Y. Li contributed equally to this paper.

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Navid, M.T., Li, Y., Zhou, M. et al. Comparison of the immunogenicity of two inactivated recombinant rabies viruses overexpressing the glycoprotein. Arch Virol 161, 2863–2870 (2016). https://doi.org/10.1007/s00705-016-2967-8

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  • DOI: https://doi.org/10.1007/s00705-016-2967-8

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