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Vaccine Strategy That Enhances the Protective Efficacy of Systemic Immunization by Establishing Lung-Resident Memory CD8 T Cells Against Influenza Infection

  • Hyun-Jung Kong (Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Youngwon Choi (Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Eun-Ah Kim (Graduate School of Pharmaceutical Sciences, Ewha Womans University) ;
  • Jun Chang (Graduate School of Pharmaceutical Sciences, Ewha Womans University)
  • Received : 2022.12.27
  • Accepted : 2023.07.31
  • Published : 2023.08.31
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Abstract

Most influenza vaccines currently in use target the highly variable hemagglutinin protein to induce neutralizing antibodies and therefore require yearly reformulation. T cell-based universal influenza vaccines focus on eliciting broadly cross-reactive T-cell responses, especially the tissue-resident memory T cell (TRM) population in the respiratory tract, providing superior protection to circulating memory T cells. This study demonstrated that intramuscular (i.m.) administration of the adenovirus-based vaccine expressing influenza virus nucleoprotein (rAd/NP) elicited weak CD8 TRM responses in the lungs and airways, and yielded poor protection against lethal influenza virus challenge. However, a novel "prime-and-deploy" strategy that combines i.m. vaccination of rAd/NP with subsequent intranasal administration of an empty adenovector induced strong NP-specific CD8+ TRM cells and provided complete protection against influenza virus challenge. Overall, our results demonstrate that this "prime-and-deploy" vaccination strategy is potentially applicable to the development of universal influenza vaccines.

Keywords

Acknowledgement

We are grateful to the members of the immunology laboratory for their helpful contributions and technical assistance. The authors also wish to thank all members of the HYEHWA FORUM for their helpful comments and creative motivation. This study was supported by a grant from the National Research Foundation (Grant number: NRF-2022R1A2C1003158) and Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Grant number: HV20C0049).

References

  1. Flerlage T, Boyd DF, Meliopoulos V, Thomas PG, Schultz-Cherry S. Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract. Nat Rev Microbiol 2021;19:425-441.
  2. Episcopio D, Aminov S, Benjamin S, Germain G, Datan E, Landazuri J, Lockshin RA, Zakeri Z. Atorvastatin restricts the ability of influenza virus to generate lipid droplets and severely suppresses the replication of the virus. FASEB J 2019;33:9516-9525.
  3. Krammer F, Smith GJD, Fouchier RAM, Peiris M, Kedzierska K, Doherty PC, Palese P, Shaw ML, Treanor J, Webster RG, et al. Influenza. Nat Rev Dis Primers 2018;4:3.
  4. Zambon MC. Epidemiology and pathogenesis of influenza. J Antimicrob Chemother 1999;44 Suppl B:3-9.
  5. Carrat F, Flahault A. Influenza vaccine: the challenge of antigenic drift. Vaccine 2007;25:6852-6862.
  6. Kim SK, Cornberg M, Wang XZ, Chen HD, Selin LK, Welsh RM. Private specificities of CD8 T cell responses control patterns of heterologous immunity. J Exp Med 2005;201:523-533.
  7. Zheng M, Luo J, Chen Z. Development of universal influenza vaccines based on influenza virus M and NP genes. Infection 2014;42:251-262.
  8. Ulmer JB, Fu TM, Deck RR, Friedman A, Guan L, DeWitt C, Liu X, Wang S, Liu MA, Donnelly JJ, et al. Protective CD4+ and CD8+ T cells against influenza virus induced by vaccination with nucleoprotein DNA. J Virol 1998;72:5648-5653.
  9. Flynn KJ, Belz GT, Altman JD, Ahmed R, Woodland DL, Doherty PC. Virus-specific CD8+ T cells in primary and secondary influenza pneumonia. Immunity 1998;8:683-691.
  10. Townsend AR, Skehel JJ. The influenza A virus nucleoprotein gene controls the induction of both subtype specific and cross-reactive cytotoxic T cells. J Exp Med 1984;160:552-563.
  11. Chang J. Adenovirus vectors: excellent tools for vaccine development. Immune Netw 2021;21:e6.
  12. Tatsis N, Ertl HC. Adenoviruses as vaccine vectors. Mol Ther 2004;10:616-629.
  13. Kim SH, Kim JY, Choi Y, Nguyen HH, Song MK, Chang J. Mucosal vaccination with recombinant adenovirus encoding nucleoprotein provides potent protection against influenza virus infection. PLoS One 2013;8:e75460.
  14. Lambe T, Carey JB, Li Y, Spencer AJ, van Laarhoven A, Mullarkey CE, Vrdoljak A, Moore AC, Gilbert SC. Immunity against heterosubtypic influenza virus induced by adenovirus and MVA expressing nucleoprotein and matrix protein-1. Sci Rep 2013;3:1443.
  15. Price GE, Soboleski MR, Lo CY, Misplon JA, Quirion MR, Houser KV, Pearce MB, Pappas C, Tumpey TM, Epstein SL. Single-dose mucosal immunization with a candidate universal influenza vaccine provides rapid protection from virulent H5N1, H3N2 and H1N1 viruses. PLoS One 2010;5:e13162.
  16. Zhou D, Wu TL, Lasaro MO, Latimer BP, Parzych EM, Bian A, Li Y, Li H, Erikson J, Xiang Z, et al. A universal influenza A vaccine based on adenovirus expressing matrix-2 ectodomain and nucleoprotein protects mice from lethal challenge. Mol Ther 2010;18:2182-2189.
  17. Lund FE, Randall TD. Scent of a vaccine. Science 2021;373:397-399.
  18. Bevan MJ. Memory T cells as an occupying force. Eur J Immunol 2011;41:1192-1195.
  19. Schenkel JM, Masopust D. Tissue-resident memory T cells. Immunity 2014;41:886-897.
  20. Caminschi I, Lahoud MH, Pizzolla A, Wakim LM. Zymosan by-passes the requirement for pulmonary antigen encounter in lung tissue-resident memory CD8+ T cell development. Mucosal Immunol 2019;12:403-412.
  21. Pizzolla A, Nguyen TH, Smith JM, Brooks AG, Kedzieska K, Heath WR, Reading PC, Wakim LM. Resident memory CD8+ T cells in the upper respiratory tract prevent pulmonary influenza virus infection. Sci Immunol 2017;2:eaam6970.
  22. Takamura S, Yagi H, Hakata Y, Motozono C, McMaster SR, Masumoto T, Fujisawa M, Chikaishi T, Komeda J, Itoh J, et al. Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance. J Exp Med 2016;213:3057-3073.
  23. Zens KD, Chen JK, Farber DL. Vaccine-generated lung tissue-resident memory T cells provide heterosubtypic protection to influenza infection. JCI Insight 2016;1:e85832.
  24. Zheng MZ, Wakim LM. Tissue resident memory T cells in the respiratory tract. Mucosal Immunol 2022;15:379-388.
  25. Casey KA, Fraser KA, Schenkel JM, Moran A, Abt MC, Beura LK, Lucas PJ, Artis D, Wherry EJ, Hogquist K, et al. Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues. J Immunol 2012;188:4866-4875.
  26. Wu T, Hu Y, Lee YT, Bouchard KR, Benechet A, Khanna K, Cauley LS. Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection. J Leukoc Biol 2014;95:215-224.
  27. Shin H, Iwasaki A. A vaccine strategy that protects against genital herpes by establishing local memory T cells. Nature 2012;491:463-467.
  28. Chung H, Kim EA, Chang J. "Prime and deploy" strategy for universal influenza vaccine targeting nucleoprotein induces lung-resident memory CD8 T cells. Immune Netw 2021;21:e28.
  29. Gupta N, Chaudhry R, Thakur CK. Determination of cutoff of ELISA and immunofluorescence assay for scrub typhus. J Glob Infect Dis 2016;8:97-99.
  30. Brauer R, Chen P. Influenza virus propagation in embryonated chicken eggs. J Vis Exp 2015:52421.
  31. Merten OW, Hannoun C, Manuguerra JC, Ventre F, Petres S. Production of influenza virus in cell cultures for vaccine preparation. Adv Exp Med Biol 1996;397:141-151.
  32. Tobita K, Sugiura A, Enomote C, Furuyama M. Plaque assay and primary isolation of influenza A viruses in an established line of canine kidney cells (MDCK) in the presence of trypsin. Med Microbiol Immunol 1975;162:9-14.
  33. Altman JD, Moss PA, Goulder PJ, Barouch DH, McHeyzer-Williams MG, Bell JI, McMichael AJ, Davis MM. Phenotypic analysis of antigen-specific T lymphocytes. Science 1996;274:94-96.
  34. Whelan JA, Dunbar PR, Price DA, Purbhoo MA, Lechner F, Ogg GS, Griffiths G, Phillips RE, Cerundolo V, Sewell AK. Specificity of CTL interactions with peptide-MHC class I tetrameric complexes is temperature dependent. J Immunol 1999;163:4342-4348.
  35. Reber A, Katz J. Immunological assessment of influenza vaccines and immune correlates of protection. Expert Rev Vaccines 2013;12:519-536.
  36. Nelson SA, Sant AJ. Potentiating lung mucosal immunity through intranasal vaccination. 2021;12:808527.
  37. Goldblatt D, Alter G, Crotty S, Plotkin SA. Correlates of protection against SARS-CoV-2 infection and COVID-19 disease. Immunol Rev 2022;310:6-26.
  38. Bachmann MF, Kundig TM, Hengartner H, Zinkernagel RM. Protection against immunopathological consequences of a viral infection by activated but not resting cytotoxic T cells: T cell memory without "memory T cells"? Proc Natl Acad Sci U S A 1997;94:640-645.
  39. Bachmann MF, Wolint P, Schwarz K, Oxenius A. Recall proliferation potential of memory CD8+ T cells and antiviral protection. J Immunol 2005;175:4677-4685.
  40. Wherry EJ, Teichgraber V, Becker TC, Masopust D, Kaech SM, Antia R, von Andrian UH, Ahmed R. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 2003;4:225-234.
  41. Bull MB, Gu H, Ma FN, Perera LP, Poon LL, Valkenburg SA. Next-generation T cell-activating vaccination increases influenza virus mutation prevalence. Sci Adv 2022;8:eabl5209.
  42. Mao T, Israelow B, Pena-Hernandez MA, Suberi A, Zhou L, Luyten S, Reschke M, Dong H, Homer RJ, Saltzman WM, et al. Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses. Science 2022;378:eabo2523.
  43. Mutsch M, Zhou W, Rhodes P, Bopp M, Chen RT, Linder T, Spyr C, Steffen R. Use of the inactivated intranasal influenza vaccine and the risk of Bell's palsy in Switzerland. N Engl J Med 2004;350:896-903.
  44. Tang J, Zeng C, Cox TM, Li C, Son YM, Cheon IS, Wu Y, Behl S, Taylor JJ, Chakaraborty R, et al. Respiratory mucosal immunity against SARS-CoV-2 after mRNA vaccination. Sci Immunol 2022;7:eadd4853.
  45. Lapuente D, Fuchs J, Willar J, Vieira Antao A, Eberlein V, Uhlig N, Issmail L, Schmidt A, Oltmanns F, Peter AS, et al. Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization. Nat Commun 2021;12:6871.