Publikationsserver der Universitätsbibliothek Marburg

Titel:Measles virus as vaccine platform against highly pathogenic emerging viruses
Autor:Fiedler, Anna Helena
Weitere Beteiligte: Becker, Stephan (Prof. Dr.)
Veröffentlicht:2017
URI:https://archiv.ub.uni-marburg.de/diss/z2017/0310
URN: urn:nbn:de:hebis:04-z2017-03109
DOI: https://doi.org/10.17192/z2017.0310
DDC: Medizin
Titel (trans.):Masernviren als Impfstoffplattform gegen hochpathogene neu auftretende Viren
Publikationsdatum:2017-05-31
Lizenz:https://creativecommons.org/licenses/by-nc-sa/4.0

Dokument

Schlagwörter:
Coronavirus, Impfstoffe, Institut für Virologie, Virologie, Middle East, Respiratory Syndrom, Masernviren ,

Summary:
Highly pathogenic viruses are a significant global danger since they can be spread by worldwide travel and trade almost without restriction. One particular threat comes from emerging infections, for which no adequate treatment options currently exist. To guard against local or global outbreaks of these viruses, the development of protective vaccines at an early stage is therefore a desirable form of intervention. Vector-based vaccine platforms, such as that of replication-competent recombinant measles virus (rMV), constitute good prospective vaccine candidates, since they have the potential to allow for an easy exchange of antigen-encoding genes, thereby enabling rapid vaccine production after standardisation. To assess their suitability as a potential vaccine platform against highly infectious viral pathogens, rMVs were generated as part of the practical element of this thesis. These encoded for antigens of the following emerging pathogens: Middle East respiratory syndrome coronavirus (MERS-CoV), influenza virus H7N9 or Crimean-Congo haemorrhagic fever virus (CCHFV). Insertions of antigen-encoding genes resulted in the detectable expression of the MERS-CoV spike glycoprotein in both membrane-bound (MERS-S) and soluble form (MERS-solS), the MERS-CoV nucleocapsidprotein (MERS-N), haemagluttinin or neuraminidase of H7N9 (H7 or N9), the CCHFV glycoprotein Gc (CCHFV-Gc); and the CCHFV-nucleocapsid protein (CCHFV-N), in cells infected with respective vaccines. Immunisation of MV susceptible mice with MERS-S-, MERS-solS-, H7-, or N9-encoding vaccines also resulted in the induction of humoral immune responses. These included virus-neutralising antibodies (nAbs), if mice were vaccinated with MV-MERS-S, MV-MERS-solS or MV-H7. Generation of syngeneic for the respective antigens' transgenic dendritic cell (DC) cell lines, moreover, enabled an efficient re-stimulation of antigen-specific T cells without knowledge of immunogenic epitopes or the availability of antigens as proteins. When using these transgenic DC cell lines, MV-MERS-S-, MV-MERS-solS-, MV-MERS-N-, and MV-H7-induced cellular immune responses were demonstrated in an IFN-γ-ELISpot. Moreover, MERS-S specific CD8+T cells of immunised mice responded to respective re-stimulation by MERS-S-dependent proliferation and MERS-S-specific cytotoxicity. A reduction of viral loads, as well as virus-induced inflammation of lung tissue, was observed in MV-MERS-S- or MV-MERS-solS-vaccinated mice within a MERS-CoV challenge model. This impressively demonstrated the protective efficacy of an MV-based vaccine against MERS-CoV. In the second part of this thesis, MERS-CoV-induced innate immune responses in human and murine antigen-presenting cells (APCs) were analysed. As a result, human plasmoid DCs (pDCs) were identified as a source of significant amounts of antiviral type I (IFN-α, IFN-β) and Typ III (IFN-λ) interferons (IFNs), which were secreted upon infection with MERS-CoV. As a so far exclusively-identified source of type I and III IFNs pDC might hence play a significant role in MERS-CoV-induced pathogenesis in humans. Thus, by using MERS-CoV as an example, this thesis identified several key interactions between an emerging pathogen and defined immune cells, which might prove to be of clinical significance, particularly in the future development of antiviral drugs. As potential vaccine candidate, an MV-based vaccine platform was generated as part of this thesis; and its protection efficacy was demonstrated. A rapidly conducted production of MV-based vaccine platforms against three different viral pathogens, an efficient induction of humoral and cellular immunity as well as protection efficacy in a challenge model indicated the potential of recombinant MV to be used as an effective vaccine platform to protect against emerging viral pathogens.

Bibliographie / References

  1. 10. Corman VM, Jores J, Meyer B, Younan M, Liljander A, Said MY, Gluecks I, Lattwein E, Bosch B, Drexler JF, Bornstein S, Drosten C, Müller MA. 2014. Antibodies against MERS coronavirus in dromedary camels, Kenya, 1992-2013. Emerg Infect Dis 20:1319 -1322. http://dx.doi .org/10.3201/eid2008.140596.
  2. 17. Bai B, Lu X, Meng J, Hu Q, Mao P, Lu B, Chen Z, Yuan Z, Wang H. 2008. Vaccination of mice with recombinant baculovirus expressing spike or nucleocapsid protein of SARS-like coronavirus generates humoral and cellular immune responses. Mol Immunol 45:868 - 875. http://dx.doi.org /10.1016/j.molimm.2007.08.010.
  3. 12. Azhar EI, El-Kafrawy SA, Farraj SA, Hassan AM, Al-Saeed MS, Hashem AM, Madani TA. 2014. Evidence for camel-to-human transmission of MERS coronavirus. N Engl J Med 370:2499 -2505. http://dx.doi.org/10 .1056/NEJMoa1401505.
  4. 51. De Becker G, Moulin V, Tielemans F, De Mattia F, Urbain J, Leo O, Moser M. 1998. Regulation of T helper cell differentiation in vivo by soluble and membrane proteins provided by antigen-presenting cells. Eur J Immunol 28:3161-3171. http://dx.doi.org/10.1002/(SICI)1521 -4141(199810)28:10,3161::AID-IMMU3161.3.0.CO;2-Q.
  5. 34. Griffin DE. 2002. Measles virus. In Encyclopedia of molecular medicine. John Wiley & Sons, Inc., Hoboken, NJ. http://dx.doi.org/10.1002/0471203076 .emm0739.
  6. 63. Kreiter S, Konrad T, Sester M, Huber C, Tureci O, Sahin U. 2007. Simultaneous ex vivo quantification of antigen-specific CD41 and CD81 T cell responses using in vitro transcribed RNA. Cancer Immunol Immunother 56:1577-1587. http://dx.doi.org/10.1007/s00262-007-0302-7.
  7. 7. Ferguson NM, Van Kerkhove MD. 2014. Identification of MERS-CoV in dromedary camels. Lancet Infect Dis 14:93-94. http://dx.doi.org/10.1016 /S1473-3099(13)70691-1.
  8. 74. Scott P. 1993. Selective differentiation of CD41 T helper cell subsets. Curr Opin Immunol 5:391-397. http://dx.doi.org/10.1016/0952 -7915(93)90058-Z.
  9. 21. Hofmann H, Pöhlmann S. 2004. Cellular entry of the SARS coronavirus. Trends Microbiol 12:466 - 472. http://dx.doi.org/10.1016/j.tim.2004.08 .008.
  10. 80. Czub M, Weingartl H, Czub S, He R, Cao J. 2005. Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets. Vaccine 23:2273-2279. http://dx.doi.org/10.1016/j.vaccine.2005.01 .033.
  11. 19. Liniger M, Zuniga A, Tamin A, Azzouz-Morin TN, Knuchel M, Marty RR, Wiegand M, Weibel S, Kelvin D, Rota PA, Naim HY. 2008. Induction of neutralising antibodies and cellular immune responses against SARS coronavirus by recombinant measles viruses. Vaccine 26: 2164 -2174. http://dx.doi.org/10.1016/j.vaccine.2008.01.057.
  12. 44. Brandler S, Ruffie C, Najburg V, Frenkiel M, Bedouelle H, Desprès P, Tangy F. 2010. Pediatric measles vaccine expressing a dengue tetravalent antigen elicits neutralizing antibodies against all four dengue viruses. Vaccine 28:6730 - 6739. http://dx.doi.org/10.1016/j.vaccine.2010.07.073.
  13. 45. Brandler S, Ruffié C, Combredet C, Brault J, Najburg V, Prevost M, Habel A, Tauber E, Desprès P, Tangy F. 2013. A recombinant measles vaccine expressing Chikungunya virus-like particles is strongly immunogenic and protects mice from lethal challenge with Chikungunya virus. Vaccine 31:3718 -3725. http://dx.doi.org/10.1016/j.vaccine.2013.05.086.
  14. 67. Coleman CM, Liu YV, Mu H, Taylor JK, Massare M, Flyer DC, Glenn GM, Smith GE, Frieman MB. 2014. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine 32:3169 -3174. http://dx.doi.org/10.1016/j.vaccine.2014.04.016.
  15. 23. Kim E, Okada K, Kenniston T, Raj VS, AlHajri MM, Farag Elmoubasher ABA, AlHajri F, Osterhaus Albert DME, Haagmans BL, Gambotto A. 2014. Immunogenicity of an adenoviral-based Middle East respiratory syndrome coronavirus vaccine in BALB/c mice. Vaccine 32: 5975-5982. http://dx.doi.org/10.1016/j.vaccine.2014.08.058.
  16. 77. Yeung Y, Yip C, Hon C, Chow Ken YC, Ma Iris CM, Zeng F, Leung Frederick CC. 2008. Transcriptional profiling of Vero E6 cells overexpressing SARS-CoV S2 subunit: insights on viral regulation of apoptosis and proliferation. Virology 371:32- 43. http://dx.doi.org/10.1016/j.virol .2007.09.016.
  17. 18. Du L, Zhao G, Chan Chris CS, Sun S, Chen M, Liu Z, Guo H, He Y, Zhou Y, Zheng B, Jiang S. 2009. Recombinant receptor-binding domain of SARS-CoV spike protein expressed in mammalian, insect and E. coli cells elicits potent neutralizing antibody and protective immunity. Virology 393:144 -150. http://dx.doi.org/10.1016/j.virol.2009.07.018.
  18. 78. Liu R, Wu L, Huang B, Huang J, Zhang Y, Ke M, Wang J, Tan W, Zhang R, Chen H, Zeng Y, Huang W. 2005. Adenoviral expression of a truncated S1 subunit of SARS-CoV spike protein results in specific humoral immune responses against SARS-CoV in rats. Virus Res 112:24 -31. http://dx.doi.org/10.1016/j.virusres.2005.02.009.
  19. 33. Hilleman MR. 2001. Current overview of the pathogenesis and prophylaxis of measles with focus on practical implications. Vaccine 20:651- 665. http://dx.doi.org/10.1016/S0264-410X(01)00384-X.
  20. 20. Dimitrov DS. 2004. Virus entry: molecular mechanisms and biomedical applications. Nat Rev Microbiol 2:109 -122. http://dx.doi.org/10.1038 /nrmicro817.
  21. 62. Kuhn AN, Diken M, Kreiter S, Selmi A, Kowalska J, Jemielity J, Darzynkiewicz E, Huber C, Tureci O, Sahin U. 2010. Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo. Gene Ther 17:961-971. http://dx.doi.org/10.1038/gt.2010.52.
  22. 58. Münch RC, Mühlebach MD, Schaser T, Kneissl S, Jost C, Plückthun A, Cichutek K, Buchholz CJ. 2011. DARPins: an efficient targeting domain for lentiviral vectors. Mol Ther 19:686 - 693. http://dx.doi.org/10.1038/mt .2010.298.
  23. 61. Funke S, Maisner A, Mühlebach MD, Koehl U, Grez M, Cattaneo R, Cichutek K, Buchholz CJ. 2008. Targeted cell entry of lentiviral vectors. Mol Ther 16:1427-1436. http://dx.doi.org/10.1038/mt.2008.128.
  24. 25. Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, Muth D, Demmers JA, Zaki A, Fouchier RA, Thiel V, Drosten C, Rottier PJ, Osterhaus AD, Bosch BJ, Haagmans BL. 2013. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus EMC. Nature 495:251-254. http://dx.doi.org/10.1038/nature12005.
  25. 57. Zufferey R, Nagy D, Mandel RJ, Naldini L, Trono D. 1997. Multiply attenuated lentiviral vector achieves efficient gene delivery in vivo. Nat Biotechnol 15:871- 875. http://dx.doi.org/10.1038/nbt0997-871.
  26. 16. Peiris JSM, Guan Y, Yuen KY. 2004. Severe acute respiratory syndrome. Nat Med 10:S88 -S97. http://dx.doi.org/10.1038/nm1143.
  27. 89. Jones SM, Feldmann H, Stroher U, Geisbert JB, Fernando L, Grolla A, Klenk H, Sullivan NJ, Volchkov VE, Fritz EA, Daddario KM, Hensley LE, Jahrling PB, Geisbert TW. 2005. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses. Nat Med 11:786 -790. http://dx.doi.org/10.1038/nm1258.
  28. 1. Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RM. 2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367:1814 -1820. http://dx.doi.org/10.1056 /NEJMoa1211721.
  29. 3. Drosten C, Meyer B, Müller MA, Corman VM, Al-Masri M, Hossain R, Madani H, Sieberg A, Bosch BJ, Lattwein E, Alhakeem RF, Assiri AM, Hajomar W, Albarrak AM, Al-Tawfiq JA, Zumla AI, Memish ZA. 2014. Transmission of MERS-coronavirus in household contacts. N Engl J Med 371:828 - 835. http://dx.doi.org/10.1056/NEJMoa1405858.
  30. 55. Hewett JW, Tannous B, Niland BP, Nery FC, Zeng J, Li Y, Breakefield XO. 2007. Mutant torsin A interferes with protein processing through the secretory pathway in DYT1 dystonia cells. Proc Natl Acad Sci U S A 104: 7271-7276. http://dx.doi.org/10.1073/pnas.0701185104.
  31. 56. Boussif O, Lezoualc'h F, Zanta MA, Mergny MD, Scherman D, Demeneix B, Behr JP. 1995. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine. Proc Natl Acad Sci U S A 92:7297-7301. http://dx.doi.org/10.1073/pnas.92.16.7297.
  32. 42. Desprès P, Combredet C, Frenkiel M, Lorin C, Brahic M, Tangy F. 2005. Live measles vaccine expressing the secreted form of the West Nile virus envelope glycoprotein protects against West Nile virus encephalitis. J Infect Dis 191:207-214. http://dx.doi.org/10.1086/426824.
  33. 87. Tangy F, Naim HY. 2005. Live attenuated measles vaccine as a potential multivalent pediatric vaccination vector. Viral Immunol 18:317-326. http://dx.doi.org/10.1089/vim.2005.18.317.
  34. 43. Brandler S, Marianneau P, Loth P, Lacôte S, Combredet C, Frenkiel M, Desprès P, Contamin H, Tangy F. 2012. Measles vaccine expressing the secreted form of West Nile virus envelope glycoprotein induces protective immunity in squirrel monkeys, a new model of West Nile virus infection. J Infect Dis 206:212-219. http://dx.doi.org/10.1093/infdis/jis328.
  35. 72. Leopardi R, Hyypiä T, Vainionpää R. 1992. Effect of interferon-alpha on measles virus replication in human peripheral blood mononuclear cells. APMIS 100:125-131. http://dx.doi.org/10.1111/j.1699-0463 .1992.tb00850.x.
  36. 41. Lorin C, Mollet L, Delebecque F, Combredet C, Hurtrel B, Charneau P, Brahic M, Tangy F. 2004. A single injection of recombinant measles virus vaccines expressing human immunodeficiency virus (HIV) type 1 clade B envelope glycoproteins induces neutralizing antibodies and cellular immune responses to HIV. J Virol 78:146 -157. http://dx.doi.org/10.1128 /JVI.78.1.146-157.2004.
  37. 54. Martin A, Staeheli P, Schneider U. 2006. RNA polymerase II-controlled expression of antigenomic RNA enhances the rescue efficacies of two different members of the Mononegavirales independently of the site of viral genome replication. J Virol 80:5708 -5715. http://dx.doi.org/10.1128/JVI .02389-05.
  38. 24. Gierer S, Bertram S, Kaup F, Wrensch F, Heurich A, Krämer-Kühl A, Welsch K, Winkler M, Meyer B, Drosten C, Dittmer U, Hahn T von, Simmons G, Hofmann H, Pöhlmann S. 2013. The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies. J Virol 87:5502-5511. http://dx.doi.org/10.1128/JVI.00128-13.
  39. 48. del Valle JR, Devaux P, Hodge G, Wegner NJ, McChesney MB, Cattaneo R. 2007. A vectored measles virus induces hepatitis B surface antigen antibodies while protecting macaques against measles virus challenge. J Virol 81:10597-10605. http://dx.doi.org/10.1128/JVI.00923-07.
  40. 29. Du L, Zhao G, Kou Z, Ma C, Sun S, Poon VK, Lu L, Wang L, Debnath AK, Zheng B, Zhou Y, Jiang S. 2013. Identification of a receptor-binding domain in the S protein of the novel human coronavirus Middle East respiratory syndrome coronavirus as an essential target for vaccine development. J Virol 87:9939 -9942. http://dx.doi.org/10.1128/JVI.01048-13.
  41. 13. Lau SK, Li KS, Tsang AK, Lam CS, Ahmed S, Chen H, Chan K, Woo Patrick C, Yuen KY. 2013. Genetic characterization of betacoronavirus lineage C viruses in bats reveals marked sequence divergence in the spike protein of pipistrellus bat coronavirus HKU5 in Japanese pipistrelle: implications for the origin of the novel Middle East respiratory syndrome coronavirus. J Virol 87:8638 - 8650. http://dx.doi.org/10.1128/JVI.01055-13.
  42. 22. Song F, Fux R, Provacia LB, Volz A, Eickmann M, Becker S, Osterhaus Albert DME, Haagmans BL, Sutter G. 2013. Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus-neutralizing antibodies. J Virol 87: 11950 -11954. http://dx.doi.org/10.1128/JVI.01672-13.
  43. 86. Agrawal AS, Garron T, Tao X, Peng B, Wakamiya M, Chan T, Couch RB, Tseng CK. 2015. Generation of transgenic mouse model of Middle East respiratory syndrome-coronavirus infection and disease. J Virol 89: 3659 -3670. http://dx.doi.org/10.1128/JVI.03427-14.
  44. 82. Subbarao K, McAuliffe J, Vogel L, Fahle G, Fischer S, Tatti K, Packard M, Shieh W, Zaki S, Murphy B. 2004. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice. J Virol 78:3572- 3577. http://dx.doi.org/10.1128/JVI.78.7.3572-3577.2004.
  45. 49. Bajenoff M, Germain RN. 2009. B-cell follicle development remodels the conduit system and allows soluble antigen delivery to follicular dendritic cells. Blood 114:4989 - 4997. http://dx.doi.org/10.1182 /blood-2009-06-229567.
  46. 28. Du L, Kou Z, Ma C, Tao X, Wang L, Zhao G, Chen Y, Yu F, Tseng CK, Zhou Y, Jiang S. 2013. A truncated receptor-binding domain of MERSCoV spike protein potently inhibits MERS-CoV infection and induces strong neutralizing antibody responses: implication for developing therapeutics and vaccines. PLoS One 8:e81587. http://dx.doi.org/10.1371 /journal.pone.0081587.
  47. 37. Duprex WP, Rima BK. 2002. Using green fluorescent protein to monitor measles virus cell-to-cell spread by time-lapse confocal microscopy. Methods Mol Biol 183:297-307. http://dx.doi.org/10.1385/1-59259-280 -5:297.
  48. 84. Yu L, Liu W, Schnitzlein WM, Tripathy DN, Kwang J. 2001. Study of protection by recombinant fowl poxvirus expressing C-terminal nucleocapsid protein of infectious bronchitis virus against challenge. Avian Dis 45:340 -348. http://dx.doi.org/10.2307/1592973.
  49. 5. Cowling BJ, Park M, Fang VJ, Wu P, Leung GM, Wu JT. 2015. Preliminary epidemiological assessment of MERS-CoV outbreak in South Korea, May to June. Euro Surveill 20:pii52113. http://dx.doi.org/10.289 07/1560-7917.ES2015.25.21163.
  50. 6. Raj VS, Farag EA, Reusken CB, Lamers MM, Pas SD, Voermans J, 11664 jvi.asm.org Smits SL, Osterhaus AD, Al-Mawlawi N, Al-Romaihi HE, Al Hajri MM, El-Sayed AM, Mohran KA, Ghobashy H, Al Hajri F, Al-Thani M, Al-Marri SA, El-Maghraby MM, Koopmans MP, Haagmans BL. 2014. Isolation of MERS coronavirus from a dromedary camel, Qatar, 2014. Emerg Infect Dis 20:1339 -1342. http://dx.doi.org/10.3201 /eid2008.140663.
  51. 14. Annan A, Baldwin HJ, Corman VM, Klose SM, Owusu M, Nkrumah EE, Badu EK, Anti P, Agbenyega O, Meyer B, Oppong S, Sarkodie YA, Kalko Elisabeth KV, Lina Peter HC, Godlevska EV, Reusken C, Seebens A, Gloza-Rausch F, Vallo P, Tschapka M, Drosten C, Drexler JF. 2013. Human betacoronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe. Emerg Infect Dis 19:456 - 459. http://dx.doi.org/10.3201/eid1903 .121503.
  52. 11. Memish ZA, Cotten M, Meyer B, Watson SJ, Alsahafi AJ, Al Rabeeah Abdullah A, Corman VM, Sieberg A, Makhdoom HQ, Assiri A, Al Masri M, Aldabbagh S, Bosch B, Beer M, Müller MA, Kellam P, Drosten C. 2014. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis 20:1012- 1015. http://dx.doi.org/10.3201/eid2006.140402.
  53. 73. Mills CD, Kincaid K, Alt JM, Heilman MJ, Hill AM. 2000. M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164:6166 - 6173. http://dx.doi.org/10.4049/jimmunol.164.12.6166.
  54. 38. Singh M, Billeter MA. 1999. A recombinant measles virus expressing biologically active human interleukin-12. J Gen Virol 80:101-106. http: //dx.doi.org/10.1099/0022-1317-80-1-101.
  55. 39. Singh M, Cattaneo R, Billeter MA. 1999. A recombinant measles virus expressing hepatitis B virus surface antigen induces humoral immune responses in genetically modified mice. J Virol 73:4823- 4828.
  56. 53. Shen Z, Reznikoff G, Dranoff G, Rock KL. 1997. Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J Immunol 158:2723-2730.
  57. 65. Corman VM, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M, van Boheemen S, Gopal R, Ballhause M, Bestebroer TM, Muth D, Muller MA, Drexler JF, Zambon M, Osterhaus AD, Fouchier RM, Drosten C. 2012. Detection of a novel human coronavirus by real-time reversetranscription polymerase chain reaction. Euro Surveill 17:pii-20285. http: //www.eurosurveillance.org/ViewArticle.aspx?ArticleId520285.
  58. 52. Enriquez-Rincon F, Klaus GG. 1984. Differing effects of monoclonal anti-hapten antibodies on humoral responses to soluble or particulate antigens. Immunology 52:129 -136.
  59. 47. Ramsauer K, Schwameis M, Firbas C, Müllner M, Putnak RJ, Thomas SJ, Desprès P, Tauber E, Jilma B, Tangy F. 2015. Immunogenicity, safety, and tolerability of a recombinant measles-virus-based Chikungunya vaccine: a randomised, double-blind, placebo-controlled, activecomparator, first-in-man trial. Lancet Infect Dis 15:519 -527. http://dx .doi.org/10.1016/S1473-3099(15)70043-5.
  60. 81. An S, Chen CJ, Yu X, Leibowitz JL, Makino S. 1999. Induction of apoptosis in murine coronavirus-infected cultured cells and demonstration of E protein as an apoptosis inducer. J Virol 73:7853-7859.
  61. 27. Ma C, Li Y, Wang L, Zhao G, Tao X, Tseng CK, Zhou Y, Du L, Jiang S. 2014. Intranasal vaccination with recombinant receptor-binding domain of MERS-CoV spike protein induces much stronger local mucosal immune responses than subcutaneous immunization: implication for designing novel mucosal MERS vaccines. Vaccine 32:2100 -2108. http://dx .doi.org/10.1016/j.vaccine.2014.02.004.
  62. 46. Mrkic B, Pavlovic J, Rülicke T, Volpe P, Buchholz CJ, Hourcade D, Atkinson JP, Aguzzi A, Cattaneo R. 1998. Measles virus spread and pathogenesis in genetically modified mice. J Virol 72:7420 -7427.
  63. 4. Petersen E, Hui DS, Perlman S, Zumla A. 2015. Middle East respiratory syndrome: advancing the public health and research agenda on MERS. Lessons from the South Korea outbreak. Int J Infect Dis 36:54 -55. http: //dx.doi.org/10.1016/j.ijid.2015.06.004.
  64. 88. Garbutt M, Liebscher R, Wahl-Jensen V, Jones S, Moller P, Wagner R, Volchkov V, Klenk H, Feldmann H, Stroher U. 2004. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J Virol 78:5458 -5465. http://dx .doi.org/10.1128/JVI.78.10.5458-5465.2004.
  65. 35. Radecke F, Spielhofer P, Schneider H, Kaelin K, Huber M, Dötsch C, Billeter MA. 1995. Rescue of measles viruses from cloned DNA. EMBO J 14:5773-5784.
  66. 36. Billeter MA, Naim HY, Udem SA. 2009. Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses. Curr Top Microbiol Immunol 329:129 -162. http: //dx.doi.org/10.1007/978-3-540-70523-9_7.
  67. 68. Ma C, Wang L, Tao X, Zhang N, Yang Y, Tseng CK, Li F, Zhou Y, Jiang S, Du L. 2014. Searching for an ideal vaccine candidate among different MERS coronavirus receptor-binding fragments: the importance of immunofocusing in subunit vaccine design. Vaccine 32:6170 - 6176. http://dx .doi.org/10.1016/j.vaccine.2014.08.086.
  68. 75. Brenner GJ, Cohen N, Moynihan JA. 1994. Similar immune response to nonlethal infection with herpes simplex virus-1 in sensitive (BALB/c) and resistant (C57BL/6) strains of mice. Cell Immunol 157:510 -524. http://dx .doi.org/10.1006/cimm.1994.1246.
  69. 59. Bach P, Abel T, Hoffmann C, Gal Z, Braun G, Voelker I, Ball CR, Johnston Ian CD, Lauer UM, Herold-Mende C, Mühlebach MD, Glimm H, Buchholz CJ. 2013. Specific elimination of CD1331 tumor cells with targeted oncolytic measles virus. Cancer Res 73:865- 874. http: //dx.doi.org/10.1158/0008-5472.CAN-12-2221.
  70. 31. Lan J, Deng Y, Chen H, Lu G, Wang W, Guo X, Lu Z, Gao GF, Tan W. 2014. Tailoring subunit vaccine immunity with adjuvant combinations and delivery routes using the Middle East respiratory coronavirus (MERSCoV) receptor-binding domain as an antigen. PLoS One 9:e112602. http: //dx.doi.org/10.1371/journal.pone.0112602.
  71. 83. Seo SH, Wang L, Smith R, Collisson EW. 1997. The carboxyl-terminal 120-residue polypeptide of infectious bronchitis virus nucleocapsid induces cytotoxic T lymphocytes and protects chickens from acute infection. J Virol 71:7889 -7894.
  72. 30. Mou H, Raj VS, van Kuppeveld FJ, Rottier PJ, Haagmans BL, Bosch BJ. 2013. The receptor binding domain of the new Middle East respiratory syndrome coronavirus maps to a 231-residue region in the spike protein that efficiently elicits neutralizing antibodies. J Virol 87:9379 -9383. http: //dx.doi.org/10.1128/JVI.01277-13.
  73. 66. Coleman CM, Matthews KL, Goicochea L, Frieman MB. 2014. Wildtype and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus. J Gen Virol 95:408 - 412. http://dx .doi.org/10.1099/vir.0.060640-0.
  74. 2. World Health Organization. 2014. Middle East respiratory syndrome coronavirus (MERS-CoV)-Saudi Arabia. World Health Organization, Geneva, Switzerland. http://www.who.int/csr/don/17-december-2014 -mers/en/.


* Das Dokument ist im Internet frei zugänglich - Hinweise zu den Nutzungsrechten