DOI QR코드

DOI QR Code

Performance of Homologous and Heterologous Prime-Boost Immunization Regimens of Recombinant Adenovirus and Modified Vaccinia Virus Ankara Expressing an Ag85B-TB10.4 Fusion Protein against Mycobacterium tuberculosis

  • Kou, Yiming (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Wan, Mingming (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Shi, Wei (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Liu, Jie (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Zhao, Zhilei (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Xu, Yongqing (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Wei, Wei (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Sun, Bo (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Gao, Feng (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Cai, Linjun (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Jiang, Chunlai (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University)
  • 투고 : 2017.12.28
  • 심사 : 2018.04.03
  • 발행 : 2018.06.28

초록

Tuberculosis (TB) remains a serious health issue around the word. Adenovirus (Ad)-based vaccine and modified vaccinia virus Ankara (MVA)-based vaccine have emerged as two of the most promising immunization candidates over the past few years. However, the performance of the homologous and heterologous prime-boost immunization regimens of these two viral vector-based vaccines remains unclear. In the present study, we constructed recombinant Ad and MVA expressing an Ag85B-TB10.4 fusion protein (AdH4 and MVAH4) and evaluated the impact of their different immunization regimens on the humoral and cellular immune responses. We found that the viral vector-based vaccines could generate significantly higher levels of antigen-specific antibodies, $IFN-{\gamma}$-producing splenocytes, $CD69^+CD8^+$ T cells, and $IFN-{\gamma}$ secretion when compared with bacillus Calmette-$Gu{\acute{e}}rin$ (BCG) in a mouse model. AdH4-containing immunization regimens (AdH4-AdH4, AdH4-MVAH4, and MVAH4-AdH4) induced significantly stronger antibody responses, much more $IFN-{\gamma}$-producing splenocytes and $CD69^+CD8^+$ T cells, and higher levels of $IFN-{\gamma}$ secretion when compared with the MVAH4-MVAH4 immunization regimen. The number of $IFN-{\gamma}$-producing splenocytes sensitive to $CD8^+$ T-cell restricted peptides of Ag85B (9-1p and 9-2p) and Th1-related cytokines ($IFN-{\gamma}$ and $TNF-{\alpha}$) in the AdH4-MVAH4 heterologous prime-boost regimen immunization group was significantly higher than that in the other viral vector-based vaccine- and BCG-immunized groups, respectively. These results indicate that an immunization regimen involving AdH4 may have a higher capacity to induce humoral and cellular immune responses against TB in mice than that by regimens containing BCG or MVAH4 alone, and the AdH4-MVAH4 prime-boost regimen may generate an ideal protective effect.

키워드

참고문헌

  1. WHO. Global tuberculosis report 2017. Available from http://www.who.int/tb/publications/global_report/en/. Accessed March 09, 2018.
  2. Brewer TF. 2000. Preventing tuberculosis with bacillus Calmette-Guerin vaccine: a meta-analysis of the literature. Clin. Infect. Dis. 31: S64-S67. https://doi.org/10.1086/314072
  3. Xie Y, Chakravorty S, Armstrong D, Hall S, Via L, Song T, et al. 2017. Evaluation of a rapid molecular drug-susceptibility test for tuberculosis. N. Engl. J. Med. 377: 1043-1054. https://doi.org/10.1056/NEJMoa1614915
  4. Triccas JA, Counoupas C. 2016. Novel vaccination approaches to prevent tuberculosis in children. Pneumonia (Nathan) 8: 18. https://doi.org/10.1186/s41479-016-0020-z
  5. Bo M, Zotti CM. 2016. European policies on tuberculosis prevention in healthcare workers: which role for BCG? A systematic review. Hum. Vaccin. Immunother. 12: 2753-2764. https://doi.org/10.1080/21645515.2016.1200776
  6. Mendez-Samperio P. 2016. Global efforts in the development of vaccines for tuberculosis: requirements for improved vaccines against Mycobacterium tuberculosis. Scand. J. Immunol. 84: 204-210. https://doi.org/10.1111/sji.12465
  7. You Q, Wu Y, Wu Y, Wei W, Wang C, Jiang D, et al. 2012. Immunogenicity and protective efficacy of heterologous prime-boost regimens with mycobacterial vaccines and recombinant adenovirus- and poxvirus-vectored vaccines against murine tuberculosis. Int. J. Infect. Dis. 16: e816-e825. https://doi.org/10.1016/j.ijid.2012.07.008
  8. Dean G, Clifford D, Gilbert S, McShane H, Hewinson RG, Vordermeier HM, et al. 2014. Effect of dose and route of immunisation on the immune response induced in cattle by heterologous Bacille Calmette-Guerin priming and recombinant adenoviral vector boosting. Vet. Immunol. Immunopathol. 158: 208-213. https://doi.org/10.1016/j.vetimm.2014.01.010
  9. Stylianou E, Griffiths KL, Poyntz HC, Harrington-Kandt R, Dicks MD, Stockdale L, et al. 2015. Improvement of BCG protective efficacy with a novel chimpanzee adenovirus and a modified vaccinia Ankara virus both expressing Ag85A. Vaccine 33: 6800-6808. https://doi.org/10.1016/j.vaccine.2015.10.017
  10. Minhinnick A, Satti I, Harris S, Wilkie M, Sheehan S, Stockdale L, et al. 2016. A first-in-human phase 1 trial to evaluate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-IMX313, administered to BCG-vaccinated adults. Vaccine 34: 1412-1421. https://doi.org/10.1016/j.vaccine.2016.01.062
  11. Nemes E, Hesseling AC, Tameris M, Mauff K, Downing K, Mulenga H, et al. 2018. Safety and immunogenicity of newborn MVA85A vaccination and selective, delayed bacille Calmette-Guerin for infants of human immunodeficiency virus-infected mothers: a phase 2 randomized, controlled trial. Clin. Infect. Dis. 66: 554-563. https://doi.org/10.1093/cid/cix834
  12. Tye GJ, Lew MH, Choong YS, Lim TS, Sarmiento ME, Acosta A, et al. 2015. Vaccines for TB: lessons from the past translating into future potentials. Clin. Dev. Immunol. 2015: 916780.
  13. Billeskov R, Christensen JP, Aagaard C, Andersen P, Dietrich J. 2013. Comparing adjuvanted H28 and modified vaccinia virus Ankara expressing H28 in a mouse and a non-human primate tuberculosis model. PLoS One 8: e72185. https://doi.org/10.1371/journal.pone.0072185
  14. Luabeya AK, Kagina BM, Tameris MD, Geldenhuys H, Hoff ST, Shi Z, et al. 2015. First-in-human trial of the postexposure tuberculosis vaccine H56:IC31 in Mycobacterium tuberculosis infected and non-infected healthy adults. Vaccine 33: 4130-4140. https://doi.org/10.1016/j.vaccine.2015.06.051
  15. Li W, Deng G, Li M, Zeng J, Zhao L, Liu X, et al. 2014. A recombinant adenovirus expressing CFP10, ESAT6, Ag85A and Ag85B of Mycobacterium tuberculosis elicits strong antigen-specific immune responses in mice. Mol. Immunol. 62: 86-95. https://doi.org/10.1016/j.molimm.2014.06.007
  16. Harth G, Lee BY, Wang J, Clemens DL, Horwitz MA. 1996. Novel insights into the genetics, biochemistry, and immunocytochemistry of the 30-kilodalton major extracellular protein of Mycobacterium tuberculosis. Infect. Immun. 64: 3038- 3047.
  17. Karbalaei Zadeh Babaki M, Soleimanpour S, Rezaee SA. 2017. Antigen 85 complex as a powerful Mycobacterium tuberculosis immunogene: biology, immune-pathogenicity, applications in diagnosis, and vaccine design. Microb. Pathog. 112: 20-29. https://doi.org/10.1016/j.micpath.2017.08.040
  18. Lin PL, Dietrich J, Tan E, Abalos RM, Burgos J, Bigbee C, et al. 2012. The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection. J. Clin. Invest. 122: 303-314. https://doi.org/10.1172/JCI46252
  19. Agger EM, Rosenkrands I, Olsen AW, Hatch G, Williams A, Kritsch C, et al. 2006. Protective immunity to tuberculosis with Ag85B-ESAT-6 in a synthetic cationic adjuvant system IC31. Vaccine 24: 5452-5460. https://doi.org/10.1016/j.vaccine.2006.03.072
  20. Ko A, Wui SR, Ryu JI, Lee YJ, Hien DTT, Rhee I, et al. 2018. Potentiation of Th1-type immune responses to Mycobacterium tuberculosis antigens in mice by cationic liposomes combined with de-O-acylated lipooligosaccharide. J. Microbiol. Biotechnol. 28: 136-144.
  21. Dietrich J, Aagaard C, Leah R, Olsen AW, Stryhn A, Doherty TM, et al. 2005. Exchanging ESAT6 with TB10.4 in an Ag85B fusion molecule-based tuberculosis subunit vaccine: efficient protection and ESAT6-based sensitive monitoring of vaccine efficacy. J. Immunol. 174: 6332-6339. https://doi.org/10.4049/jimmunol.174.10.6332
  22. Billeskov R, Elvang TT, Andersen PL, Dietrich J. 2012. The HyVac4 subunit vaccine efficiently boosts BCG-primed antimycobacterial protective immunity. PLoS One 7: e39909. https://doi.org/10.1371/journal.pone.0039909
  23. Skeiky YA, Dietrich J, Lasco TM, Stagliano K, Dheenadhayalan V, Goetz MA, et al. 2010. Non-clinical efficacy and safety of HyVac4:IC31 vaccine administered in a BCG prime-boost regimen. Vaccine 28: 1084-1093. https://doi.org/10.1016/j.vaccine.2009.10.114
  24. Geldenhuys H, Mearns H, Miles DJ, Tameris M, Hokey D, Shi Z, et al. 2015. The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: a randomized controlled trial. Vaccine 33: 3592-3599. https://doi.org/10.1016/j.vaccine.2015.05.036
  25. Kou Y, Xu Y, Zhao Z, Liu J, Wu Y, You Q, et al. 2017. Tissue plasminogen activator (tPA) signal sequence enhances immunogenicity of MVA-based vaccine against tuberculosis. Immunol. Lett. 190: 51-57. https://doi.org/10.1016/j.imlet.2017.07.007
  26. You Q, Jiang C, Wu Y, Yu X, Chen Y, Zhang X, et al. 2012. Subcutaneous administration of modified vaccinia virus Ankara expressing an Ag85B-ESAT6 fusion protein, but not an adenovirus-based vaccine, protects mice against intravenous challenge with Mycobacterium tuberculosis. Scand. J. Immunol. 75: 77-84. https://doi.org/10.1111/j.1365-3083.2011.02629.x
  27. Billeskov R, Grandal MV, Poulsen C, Christensen JP, Winther N, Vingsbo-Lundberg C, et al. 2010. Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis. Eur. J. Immunol. 40: 1342-1354. https://doi.org/10.1002/eji.200939830
  28. Radosevic K, Wieland CW, Rodriguez A, Weverling GJ, Mintardjo R, Gillissen G, et al. 2007. Protective immune responses to a recombinant adenovirus type 35 tuberculosis vaccine in two mouse strains: CD4 and CD8 T-cell epitope mapping and role of gamma interferon. Infect. Immun. 75: 4105-4115. https://doi.org/10.1128/IAI.00004-07
  29. Rollier CS, Hill AVS, Reyes-Sandoval A. 2016. Influence of adenovirus and MVA vaccines on the breadth and hierarchy of T cell responses. Vaccine 34: 4470-4474. https://doi.org/10.1016/j.vaccine.2016.07.050
  30. Zeng G, Zhang G, Chen X. 2018. Th1 cytokines, true functional signatures for protective immunity against TB? Cell. Mol. Immunol. 15: 206-215. https://doi.org/10.1038/cmi.2017.113
  31. Pillai VK, Kannanganat S, Penaloza-Macmaster P, Chennareddi L, Robinson HL, Blackwell J, et al. 2011. Different patterns of expansion, contraction and memory differentiation of HIV-1 Gag-specific CD8 T cells elicited by adenovirus type 5 and modified vaccinia Ankara vaccines. Vaccine 29: 5399-5406. https://doi.org/10.1016/j.vaccine.2011.05.083
  32. Maeda K, West K, Hayasaka D, Ennis FA, Terajima M. 2005. Recombinant adenovirus vector vaccine induces stronger cytotoxic T-cell responses than recombinant vaccinia virus vector, plasmid DNA, or a combination of these. Viral Immunol. 18: 657-667. https://doi.org/10.1089/vim.2005.18.657
  33. Betts G, Poyntz H, Stylianou E, Reyes-Sandoval A, Cottingham M, Hill A, et al. 2012. Optimising immunogenicity with viral vectors: mixing MVA and HAdV-5 expressing the mycobacterial antigen Ag85A in a single injection. PLoS One 7: e50447. https://doi.org/10.1371/journal.pone.0050447