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Improved Immune Response to Recombinant Influenza Nucleoprotein Formulated with ISCOMATRIX

  • Cargnelutti, Diego E. (Institute of Experimental Medicine and Biology of Cuyo (IMBECU- CONICET)) ;
  • Sanchez, Maria V. (Institute of Experimental Medicine and Biology of Cuyo (IMBECU- CONICET)) ;
  • Alvarez, Paula (Animal Virology Center, Institute of Science and Technology Dr. Cesar Milstein, CONICET) ;
  • Boado, Lorena (Animal Virology Center, Institute of Science and Technology Dr. Cesar Milstein, CONICET) ;
  • Glikmann, Graciela (Virology Laboratory, Department of Science and Technology, National University of Quilmes) ;
  • Mattion, Nora (Animal Virology Center, Institute of Science and Technology Dr. Cesar Milstein, CONICET) ;
  • Scodeller, Eduardo A. (Institute of Experimental Medicine and Biology of Cuyo (IMBECU- CONICET))
  • Received : 2011.06.10
  • Accepted : 2011.11.02
  • Published : 2012.03.28

Abstract

Current influenza vaccines elicit antibodies effective against homologous strains, but new strategies are urgently needed for protection against emerging epidemic or pandemic strains. Although influenza vaccine candidates based on the viral nucleoprotein (NP) or matrix protein do not elicit sterilizing immunity, they have the advantage of inducing immunity that may cover a larger number of viral strains. In this study, recombinant NP produced in Escherichia coli was purified and formulated in combination with the adjuvant ISCOMATRIX. This formulation increased a NP-specific immunity in mice, with a Th1 profile, and may constitute a promising low-cost influenza vaccine candidate, with ability to stimulate humoral and cellular immune responses.

Keywords

References

  1. Berthoud, T. K., M. Hamill, P. J. Lillie, L. Hwenda, K. A. Collins, K. J. Ewer, et al. 2011. Potent CD8+ T-cell immunogenicity in humans of a novel heterosubtypic influenza A vaccine, MVANP+M1. Clin. Infect. Dis. 52: 1-7. https://doi.org/10.1093/cid/ciq015
  2. Coffman, R. L., B. W. Seymour, D. A Lebman, D. D Hiraki, J. A Christiansen, B. Shrader, et al. 1998. The role of helper T cell products in mouse B cell differentiation and isotype regulation. Immunol. Rev. 102: 5-28.
  3. Dormitzer, P. R., G. Galli, F. Castellino, H. Golding, S. Khurana, G. Del Giudice, and R. Rappuoli. 2011. Influenza vaccine immunology. Immunol. Rev. 239: 167-177. https://doi.org/10.1111/j.1600-065X.2010.00974.x
  4. Durando, P., R. Iudici, C. Alicino, M. Alberti, D. D. Florentiis, F. Ansaldi, and G. Icardi. 2011. Adjuvants and alternative routes of administration towards the development of the ideal influenza vaccine. Hum. Vaccin. 7: 1-2.
  5. Ebrahimi, S. M., M. Tebianian, K. Aghaiypour, H. Nili, and A. Mirjalili. 2010. Prokaryotic expression and characterization of avian influenza A virus M2 gene as a candidate for universal recombinant vaccine against influenza A subtypes; specially H5N1 and H9N2. Mol. Biol. Rep. 37: 2909-2914. https://doi.org/10.1007/s11033-009-9851-5
  6. Furuya, Y., M. Regner, M. Lobigs, A. Koskinen, A. Mullbacher, and M. Alsharifi. 2010. Effect of inactivation method on the cross-protective immunity induced by whole 'killed' influenza A viruses and commercial vaccine preparations. J. Gen. Virol. 91: 1450-1460. https://doi.org/10.1099/vir.0.018168-0
  7. Guo, L., M. Zheng, Y. Ding, D. Li, Z. Yang, H. Wang, et al. 2010. Protection against multiple influenza A virus subtypes by intranasal administration of recombinant nucleoprotein. Arch. Virol. 155: 1765-1775. https://doi.org/10.1007/s00705-010-0756-3
  8. Hessel, A., M. Schwendinger, D. Fritz, S. Coulibaly, G. W. Holzer, N. Sabarth, et al. 2010. A pandemic influenza H1N1 live vaccine based on modified vaccinia Ankara is highly immunogenic and protects mice in active and passive immunizations. PLoS One 5: e12217. https://doi.org/10.1371/journal.pone.0012217
  9. Hurwitz, J. L., C. J. Hackett, E. C. McAndrew, and W. Gerhard. 1985. Murine TH response to influenza virus: Recognition of hemagglutinin, neuraminidase, matrix, and nucleoproteins. J. Immunol. 134: 1994-1998.
  10. Jelinek, I., J. N. Leonard, G. E. Price, K. N. Brown, A. Meyer-Manlapat, P. K Goldsmith, et al. 2011. TLR3-specific doublestranded RNA oligonucleotide adjuvants induce dendritic cell cross-presentation, CTL responses, and antiviral protection. J. Immunol. 186: 2422-2429. https://doi.org/10.4049/jimmunol.1002845
  11. Khurana, S., W. Chearwae, F. Castellino, J. Manischewitz, L. R. King, A. Honorkiewicz, et al. 2010. Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus. Sci. Transl. Med. 2: 15ra5. https://doi.org/10.1126/scitranslmed.3000624
  12. Kistner, O., B. A. Crowe, W. Wodal, A. Kerschbaum, H. Savidis-Dacho, N. Sabarth, et al. 2010. A whole virus pandemic influenza H1N1 vaccine is highly immunogenic and protective in active immunization and passive protection mouse models. PLoS One 5: e9349. https://doi.org/10.1371/journal.pone.0009349
  13. Kreijtz, J. H., Y. Suzer, R. Bodewes, A. Schwantes, G. van Amerongen, R. J. Verburgh, et al. 2010. Evaluation of a modified vaccinia virus Ankara (MVA)-based candidate pandemic influenza A/H1N1 vaccine in the ferret model. J. Gen. Virol. 91: 2745-2752. https://doi.org/10.1099/vir.0.024885-0
  14. Laddy, D. J., J. Yan, A. S. Khan, H. Andersen, A. Cohn, J. Greenhouse, et al. 2009. Electroporation of synthetic DNA antigens offers protection in nonhuman primates challenged with highly pathogenic avian influenza virus. J. Virol. 83: 4624-4630. https://doi.org/10.1128/JVI.02335-08
  15. LaMere, M. W., H. T. Lam, A. Moquin, L. Haynes, F. E. Lund, T. D. Randall, and D. A. Kaminski. 2011. Contributions of antinucleoprotein IgG to heterosubtypic immunity against influenza virus. J. Immunol. 186: 4331-4339. https://doi.org/10.4049/jimmunol.1003057
  16. LaMere, M. W., A. Moquin, F. E. Lee, R. S. Misra, P. J. Blair, L. Haynes, et al. 2011. Regulation of antinucleoprotein IgG by systemic vaccination and its effect on influenza virus clearance. J. Virol. 85: 5027-5035. https://doi.org/10.1128/JVI.00150-11
  17. Leroux-Roels, I., F. Roman, S. Forgus, C. Maes, F. De Boever, M. Dramé, et al. 2010. Priming with AS03 A-adjuvanted H5N1 influenza vaccine improves the kinetics, magnitude and durability of the immune response after a heterologous booster vaccination: An open non-randomised extension of a doubleblind randomised primary study. Vaccine 28: 849-857. https://doi.org/10.1016/j.vaccine.2009.10.017
  18. Loudon, P. T., E. J. Yager, D. T. Lynch, A. Narendran, C. Stagnar, A. M. Franchini, et al. 2010. GM-CSF increases mucosal and systemic immunogenicity of an H1N1 influenza DNA vaccine administered into the epidermis of non-human primates. PLoS One 5: e11021. https://doi.org/10.1371/journal.pone.0011021
  19. McKenzie, A., M. Watt, and C. Gittleson. 2010. ISCOMATRIX(R) vaccines: Safety in human clinical studies. Hum. Vaccin 30: 6(3).
  20. Pearse, M. J. and D. Drane. 2005. ISCOMATRIX(R) adjuvant for antigen delivery. Adv. Drug Deliv. Rev. 57: 465-474. https://doi.org/10.1016/j.addr.2004.09.006
  21. Pertmer, T. M., M. D. Eisenbraun, D. McCabe, S. K Prayaga, D. H. Fuller, and J. R. Haynes. 1995. Gene gun-based nucleic acid immunization: Elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine 13: 1427-1430. https://doi.org/10.1016/0264-410X(95)00069-D
  22. Prabakaran, M., S. Madhan, N. Prabhu, J. Qiang, and J. Kwang. 2010. Gastrointestinal delivery of baculovirus displaying influenza virus hemagglutinin protects mice against heterologous H5N1 infection. J. Virol. 84: 3201-3209. https://doi.org/10.1128/JVI.02175-09
  23. Price, G. E., M. R. Soboleski, C. Y. Lo, J. A. Misplon, M. R. Quirion, K. V. Houser, et al. 2010. Single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent H5N1, H3N2 and H1N1 viruses. PLoS One 5: e13162. https://doi.org/10.1371/journal.pone.0013162
  24. Quan, F. S., R. W. Compans, H. H. Nguyen, and S. M. Kang. 2008. Induction of heterosubtypic immunity to influenza virus by intranasal immunization. J. Virol. 82: 1350-1359. https://doi.org/10.1128/JVI.01615-07
  25. Rao, S. S., W. P. Kong, C. J. Wei, N. Van Hoeven, J. P. Gorres, M. Nason, et al. 2010. Comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene-based vaccination against H5N1 influenza in mouse and ferret. PLoS One 5: e9812. https://doi.org/10.1371/journal.pone.0009812
  26. Scheepers, K. and H. Becht. 1994. Protection of mice against an influenza virus infection by oral vaccination with viral nucleoprotein incorporated into immunostimulating complexes. Med. Microbiol. Immunol. 183: 265-278. https://doi.org/10.1007/BF00198460
  27. Schwartz, J. A., L. Buonocore, A. Suguitan Jr, M. Hunter, P. A. Marx, K. Subbarao, et al. 2010. Potent vesicular stomatitis virus-based avian influenza vaccines provide long-term sterilizing immunity against heterologous challenge. J. Virol. 84: 4611-4618. https://doi.org/10.1128/JVI.02637-09
  28. Steitz, J., P. G. Barlow, J. Hossain, E. Kim, K. Okada, T. Kenniston, et al. 2010. A candidate H1N1 pandemic influenza vaccine elicits protective immunity in mice. PLoS One 5: e10492. https://doi.org/10.1371/journal.pone.0010492
  29. Tamura, S. 2010. Studies on the usefulness of intranasal inactivated influenza vaccines. Vaccine 28: 6393-6397. https://doi.org/10.1016/j.vaccine.2010.05.019
  30. Thueng-in, K., S. Maneewatch, P. Srimanote, T. Songserm, P. Tapchaisri, N. Sookrung, et al. 2010. Heterosubtypic immunity to influenza mediated by liposome adjuvanted H5N1 recombinant protein vaccines. Vaccine 28: 6765-6777. https://doi.org/10.1016/j.vaccine.2010.07.065
  31. Tite, J. P., S. M. Russell, G. Dougan, D. O'Callaghan, I. Jones, G. Brownlee, and F. Y. Liew. 1998. Antiviral immunity induced by recombinant nucleoprotein of influenza A virus. I. Characteristics and cross-reactivity of T cell responses. J. Immunol. 141: 3980-3987.
  32. Tite, J. P., C. Hughes-Jenkins, D. O'Callaghan, G. Dougan, S. M. Russell, X. M. Gao, and F. Y. Liew. 1990. Anti-viral immunity induced by recombinant nucleoprotein of influenza A virus. II. Protection from influenza infection and mechanism of protection. Immunology 71: 202-207.
  33. Ulmer, J. B., J. J. Donnelly, S. E. Parker, G. H. Rhodes, P. L. Felgner, V. J. Dwarki, et al. 1993. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science 259: 1745-1749. https://doi.org/10.1126/science.8456302
  34. Windon, R. G., P. J. Chaplin, P. McWaters, M. Tavarnesi, M. Tzatzaris, W. G. Kimpton, et al. 2001. Local immune responses to influenza antigen are synergistically enhanced by the adjuvant ISCOMATRIX. Vaccine 20: 490-497. https://doi.org/10.1016/S0264-410X(01)00332-2
  35. Wraith, D. C. and B. A. Askonas. 1985. Induction of influenza A virus cross-reactive cytotoxic T cells by a nucleoprotein/haemagglutinin preparation. J. Gen. Virol. 66: 1327-1331. https://doi.org/10.1099/0022-1317-66-6-1327
  36. Wraith, D. C., A. E. Vessey, and B. A Askonas. 1987. Purified influenza virus nucleoprotein protects mice from lethal infection. J. Gen. Virol. 68: 433-440. https://doi.org/10.1099/0022-1317-68-2-433
  37. Yewdell, J. W., J. R. Bennink, G. L Smith, and B. Moss. 1985. Influenza A virus nucleoprotein is a major target antigen for cross-reactive anti-influenza A virus cytotoxic T lymphocytes. Proc. Natl. Acad. Sci. USA 82: 1785-1789. https://doi.org/10.1073/pnas.82.6.1785
  38. Zhou, D., T. L. Wu, M. O. Lasaro, B. P. Latimer, E. M. Parzych, A. Bian, et al. 2010. A universal influenza A vaccine based on adenovirus expressing matrix-2 ectodomain and nucleoprotein protects mice from lethal challenge. Mol. Ther. 18: 2182-2189. https://doi.org/10.1038/mt.2010.202

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