IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Mucosal Immunization with Recombinant Adenovirus Encoding Soluble Globular Head of Hemagglutinin Protects Mice Against Lethal Influenza Virus Infection

  • Kim, Joo Young (Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Choi, Youngjoo (Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Nguyen, Huan H. (Laboratory Science Division, International Vaccine Institute) ;
  • Song, Man Ki (Laboratory Science Division, International Vaccine Institute) ;
  • Chang, Jun (Graduate School of Pharmaceutical Sciences, Ewha Womans University)
  • Received : 2013.12.03
  • Accepted : 2013.12.06
  • Published : 2013.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Influenza virus is one of the major sources of respiratory tract infection. Due to antigenic drift in surface glycoproteins the virus causes annual epidemics with severe morbidity and mortality. Although hemagglutinin (HA) is one of the highly variable surface glycoproteins of the influenza virus, it remains the most attractive target for vaccine development against seasonal influenza infection because antibodies generated against HA provide virus neutralization and subsequent protection against the virus infection. Combination of recombinant adenovirus (rAd) vector-based vaccine and mucosal administration is a promising regimen for safe and effective vaccination against influenza. In this study, we constructed rAd encoding the globular head region of HA from A/Puerto Rico/8/34 virus as vaccine candidate. The rAd vaccine was engineered to express high level of the protein in secreted form. Intranasal or sublingual immunization of mice with the rAd-based vaccine candidates induced significant levels of sustained HA-specific mucosal IgA and IgG. When challenged with lethal dose of homologous virus, the vaccinated mice were completely protected from the infection. The results demonstrate that intranasal or sublingual vaccination with HA-encoding rAd elicits protective immunity against infection with homologous influenza virus. This finding underlines the potential of our recombinant adenovirus-based influenza vaccine candidate for both efficacy and rapid production.

Keywords

References

  1. Collin, N. and X. de Radigues. 2009. Vaccine production capacity for seasonal and pandemic (H1N1) 2009 influenza. Vaccine 27: 5184-5186. https://doi.org/10.1016/j.vaccine.2009.06.034
  2. Shirakawa, T. 2009. Clinical trial design for adenoviral gene therapy products. Drug News Perspect. 22: 140-145. https://doi.org/10.1358/dnp.2009.22.3.1354090
  3. Muruve, D. A. 2004. The innate immune response to adenovirus vectors. Hum. Gene Ther. 15: 1157-1166. https://doi.org/10.1089/hum.2004.15.1157
  4. Zhu, J., X. Huang, and Y. Yang. 2007. Innate immune response to adenoviral vectors is mediated by both Toll-like receptor- dependent and -independent pathways. J. Virol. 81: 3170-3180. https://doi.org/10.1128/JVI.02192-06
  5. Nociari, M., O. Ocheretina, J. W. Schoggins, and E. Falck- Pedersen. 2007. Sensing infection by adenovirus: Toll-like receptor- independent viral DNA recognition signals activation of the interferon regulatory factor 3 master regulator. J. Virol. 81: 4145-4157. https://doi.org/10.1128/JVI.02685-06
  6. Brandtzaeg, P. and R. Pabst. 2004. Let's go mucosal: communication on slippery ground. Trends Immunol. 25: 570- 577. https://doi.org/10.1016/j.it.2004.09.005
  7. Suzuki, K. and S. Fagarasan. 2008. How host-bacterial interactions lead to IgA synthesis in the gut. Trends Immunol. 29: 523-531. https://doi.org/10.1016/j.it.2008.08.001
  8. Ichinohe, T., A. Iwasaki, and H. Hasegawa. 2008. Innate sensors of influenza virus: clues to developing better intranasal vaccines. Expert Rev. Vaccines 7: 1435-1445. https://doi.org/10.1586/14760584.7.9.1435
  9. Yuki, Y. and H. Kiyono. 2003. New generation of mucosal adjuvants for the induction of protective immunity. Rev. Med. Virol. 13: 293-310. https://doi.org/10.1002/rmv.398
  10. Kunkel, E. J. and E. C. Butcher. 2003. Plasma-cell homing. Nat. Rev. Immunol. 3: 822-829. https://doi.org/10.1038/nri1203
  11. van Ginkel, F. W., R. J. Jackson, Y. Yuki, and J. R. McGhee. 2000. Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J. Immunol. 165: 4778-4782. https://doi.org/10.4049/jimmunol.165.9.4778
  12. Mutsch, M., W. Zhou, P. Rhodes, M. Bopp, R. T. Chen, T. Linder, C. Spyr, and R. Steffen. 2004. Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland. N. Engl. J. Med. 350: 896-903. https://doi.org/10.1056/NEJMoa030595
  13. Cuburu, N., M. N. Kweon, J. H. Song, C. Hervouet, C. Luci, J. B. Sun, P. Hofman, J. Holmgren, F. Anjuere, and C. Czerkinsky. 2007. Sublingual immunization induces broadbased systemic and mucosal immune responses in mice. Vaccine 25: 8598-8610. https://doi.org/10.1016/j.vaccine.2007.09.073
  14. Song, J. H., H. H. Nguyen, N. Cuburu, T. Horimoto, S. Y. Ko, S. H. Park, C. Czerkinsky, and M. N. Kweon. 2008. Sublingual vaccination with influenza virus protects mice against lethal viral infection. Proc. Natl. Acad. Sci. U. S. A. 105: 1644-1649. https://doi.org/10.1073/pnas.0708684105
  15. Kweon, M. N. 2011. Sublingual mucosa: A new vaccination route for systemic and mucosal immunity. Cytokine 54: 1-5. https://doi.org/10.1016/j.cyto.2010.12.014
  16. Shim, B. S., Y. K. Choi, C. H. Yun, E. G. Lee, Y. S. Jeon, S. M. Park, I. S. Cheon, D. H. Joo, C. H. Cho, M. S. Song, S. U. Seo, Y. H. Byun, H. J. Park, H. Poo, B. L. Seong, J. O. Kim, H. H. Nguyen, K. Stadler, D. W. Kim, K. J. Hong, C. Czerkinsky, and M. K. Song. 2011. Sublingual immunization with M2-based vaccine induces broad protective immunity against influenza. PLoS One 6: e27953. https://doi.org/10.1371/journal.pone.0027953
  17. He, T. C., S. Zhou, L. T. da Costa, J. Yu, K. W. Kinzler, and B. Vogelstein. 1998. A simplified system for generating recombinant adenoviruses. Proc. Natl. Acad. Sci. U. S. A. 95: 2509-2514. https://doi.org/10.1073/pnas.95.5.2509
  18. Wilson, I. A. and N. J. Cox. 1990. Structural basis of immune recognition of influenza virus hemagglutinin. Annu. Rev. Immunol. 8: 737-771. https://doi.org/10.1146/annurev.iy.08.040190.003513
  19. Brandtzaeg, P. 2003. Role of secretory antibodies in the defence against infections. Int. J. Med. Microbiol. 293: 3-15. https://doi.org/10.1078/1438-4221-00241
  20. Gao, W., A. C. Soloff, X. Lu, A. Montecalvo, D. C. Nguyen, Y. Matsuoka, P. D. Robbins, D. E. Swayne, R. O. Donis, J. M. Katz, S. M. Barratt-Boyes, and A. Gambotto. 2006. Protection of mice and poultry from lethal H5N1 avian influenza virus through adenovirus-based immunization. J. Virol. 80: 1959-1964. https://doi.org/10.1128/JVI.80.4.1959-1964.2006
  21. Hoelscher, M. A., S. Garg, D. S. Bangari, J. A. Belser, X. Lu, I. Stephenson, R. A. Bright, J. M. Katz, S. K. Mittal, and S. Sambhara. 2006. Development of adenoviral-vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice. Lancet 367: 475-481. https://doi.org/10.1016/S0140-6736(06)68076-8
  22. Van Kampen, K. R., Z. Shi, P. Gao, J. Zhang, K. W. Foster, D. T. Chen, D. Marks, C. A. Elmets, and D. C. Tang. 2005. Safety and immunogenicity of adenovirus-vectored nasal and epicutaneous influenza vaccines in humans. Vaccine 23: 1029-1036. https://doi.org/10.1016/j.vaccine.2004.07.043
  23. Vemula, S. V. and S. K. Mittal. 2010. Production of adenovirus vectors and their use as a delivery system for influenza vaccines. Expert Opin. Biol. Ther. 10: 1469-1487. https://doi.org/10.1517/14712598.2010.519332
  24. Yu, J. R., S. Kim, J. B. Lee, and J. Chang. 2008. Single intranasal immunization with recombinant adenovirus-based vaccine induces protective immunity against respiratory syncytial virus infection. J. Virol. 82: 2350-2357. https://doi.org/10.1128/JVI.02372-07
  25. Croyle, M. A., A. Patel, K. N. Tran, M. Gray, Y. Zhang, J. E. Strong, H. Feldmann, and G. P. Kobinger. 2008. Nasal delivery of an adenovirus-based vaccine bypasses pre-existing immunity to the vaccine carrier and improves the immune response in mice. PLoS One 3: e3548. https://doi.org/10.1371/journal.pone.0003548
  26. Domm, W., L. Brooks, H. L. Chung, C. Feng, W. J. Bowers, G. Watson, J. L. McGrath, and S. Dewhurst. 2011. Robust antigen-specific humoral immune responses to sublingually delivered adenoviral vectors encoding HIV-1 Env: association with mucoadhesion and efficient penetration of the sublingual barrier. Vaccine 29: 7080-7089. https://doi.org/10.1016/j.vaccine.2011.07.008
  27. Appledorn, D. M., Y. A. Aldhamen, S. Godbehere, S. S. Seregin, and A. Amalfitano. 2011. Sublingual administration of an adenovirus serotype 5 (Ad5)-based vaccine confirms Toll-like receptor agonist activity in the oral cavity and elicits improved mucosal and systemic cell-mediated responses against HIV antigens despite preexisting Ad5 immunity. Clin. Vaccine Immunol. 18: 150-160. https://doi.org/10.1128/CVI.00341-10

Cited by

  1. Viral vector-based influenza vaccines vol.12, pp.11, 2013, https://doi.org/10.1080/21645515.2016.1210729
  2. Baculovirus Displaying Hemagglutinin Elicits Broad Cross-Protection against Influenza in Mice vol.11, pp.3, 2013, https://doi.org/10.1371/journal.pone.0152485
  3. The Next Generation of Influenza Vaccines: Towards a Universal Solution vol.9, pp.1, 2013, https://doi.org/10.3390/vaccines9010026