Genome Replication-Incompetent Sendai Virus Vaccine Vector Against Respiratory Viral Infections That Is Capable of Eliciting a Broad Spectrum of Specific Immune Response

  • Marian Wiegand
  • Wolfgang J. Neubert


Vaccines have proven to be the most effective measure against infectious diseases. However, not every infectious disease can be prevented by vaccination at the present time. For some diseases, new vaccination strategies have to be developed because classical approaches have not been successful. Viral vectors represent one novel strategy to develop specifically designed recombinant vaccines. Many vaccines have to be applied to certain risk groups among the population that represent large parts of the population, such as infants, children, the elderly, or people with a compromised immune system. Because of the altered competence of the immune system of such individuals, the safety issue is of prime importance. In the case of viral vector-based vaccines, safety will be increased if they are rendered fully replication deficient because replication deficiency does not allow vector spreading and persistence within the vaccinees or mutation toward a more pathogenic variant. In the present chapter we first take up, as an example, respiratory syncytial virus (RSV) to discuss the past problems and future options in its vaccine development. We then illustrate our efforts to develop a genome replication-deficient Sendai virus (SeV) vaccine vector. Three essential prerequisites had to be met by such a vector: (1) complete genome replication deficiency while still being able to efficiently express the inserted vaccine antigen genes; (2) stability of viral genome and encoded trans-genes; and (3) production of the replication-deficient vector stock to a sufficiently high titer in a trans-complementing cell culture system.

Replication deficiency of SeV vector could be achieved via different modifications of components involved in the viral replication complex that consists of the viral N, P, and L proteins. The viral polymerase can operate in two ways: transcription to enable gene expression and genome replication to generate progeny genomes. The difficulty was to keep the polymerase efficiently performing transcription while its replication activity was completely switched off. Rational design and reverse genetics allowed us to analyze various SeV variants with mutations in the N, P, and L genes. Finally, uncoupling of transcription from replication could be achieved via deletion of an N-terminal part of the P protein that encodes amino acids 2 to 77. Using this vector backbone, the first prototype divalent vaccine against RSV and parainfluenza type-3 virus was developed. The vaccine showed a sufficiently high production titer and high genetic stability. It proved to be fully replication deficient while still expressing the Sendai viral and transgenes at significant levels and was able to elicit a broad spectrum of humoral and cellular immune responses in animals. This preclinical proof-of-concept should lay the ground to use this novel vector platform for specific developments of vaccines with an enhanced safety profile.


Respiratory Syncytial Virus Respiratory Syncytial Virus Infection Vaccine Vector Venezuelan Equine Encephalitis Virus Bovine Respiratory Syncytial Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Alwan WH, Record FM, Openshaw PJ (1992) CD4+ T cells clear virus but augment disease in mice infected with respiratory syncytial virus. Comparison with the effects of CD8+ T cells. Clin Exp Immunol 88(3):527–536PubMedCentralPubMedGoogle Scholar
  2. Anderson LJ, Hierholzer JC, Tsou C, Hendry RM, Fernie BF, Stone Y, McIntosh K (1985) Antigenic characterization of respiratory syncytial virus strains with monoclonal antibodies. J Infect Dis 151(4):626–633PubMedGoogle Scholar
  3. Bossow S, Schlecht S, Schubbert R, Pfeiffer M, Neubert WJ, Wiegand M (2012) Evaluation of nucleocapsid and phosphoprotein P functionality as critical factors during the early phase of paramyxoviral infection. Open Virol J 6:73–81. doi: 10.2174/1874357901206010073 PubMedCentralPubMedGoogle Scholar
  4. Boxus M, Tignon M, Roels S, Toussaint JF, Walravens K, Benoit MA, Coppe P, Letesson JJ, Letellier C, Kerkhofs P (2007) DNA immunization with plasmids encoding fusion and nucleocapsid proteins of bovine respiratory syncytial virus induces a strong cell-mediated immunity and protects calves against challenge. J Virol 81(13):6879–6889. doi: 10.1128/jvi.00502-07 PubMedCentralPubMedGoogle Scholar
  5. Buchholz CJ, Spehner D, Drillien R, Neubert WJ, Homann HE (1993) The conserved N-terminal region of Sendai virus nucleocapsid protein NP is required for nucleocapsid assembly. J Virol 67(10):5803–5812PubMedCentralPubMedGoogle Scholar
  6. Bukreyev A, Yang L, Fricke J, Cheng L, Ward JM, Murphy BR, Collins PL (2008) The secreted form of respiratory syncytial virus G glycoprotein helps the virus evade antibody-mediated restriction of replication by acting as an antigen decoy and through effects on Fc receptor-bearing leukocytes. J Virol 82(24):12191–12204. doi: 10.1128/jvi.01604-08 PubMedCentralPubMedGoogle Scholar
  7. Cadd T, Garcin D, Tapparel C, Itoh M, Homma M, Roux L, Curran J, Kolakofsky D (1996) The Sendai paramyxovirus accessory C proteins inhibit viral genome amplification in a promoter-specific fashion. J Virol 70(8):5067–5074PubMedCentralPubMedGoogle Scholar
  8. Cardenas S, Auais A, Piedimonte G (2005) Palivizumab in the prophylaxis of respiratory syncytial virus infection. Expert Rev Anti Infect Ther 3(5):719–726. doi: 10.1586/14787210.3.5.719 PubMedGoogle Scholar
  9. Cherrie AH, Anderson K, Wertz GW, Openshaw PJ (1992) Human cytotoxic T cells stimulated by antigen on dendritic cells recognize the N, SH, F, M, 22K, and 1b proteins of respiratory syncytial virus. J Virol 66(4):2102–2110PubMedCentralPubMedGoogle Scholar
  10. Collins PL, Crowe JE Jr (2007) Respiratory syncytial virus and metapneumovirus. In: Knipe DM, Howley P (eds) Fields virology, 5th edn. Lippincott Williams & Wilkins, Philadelphia, pp 1601–1646Google Scholar
  11. Connors M, Giese NA, Kulkarni AB, Firestone CY, Morse HC 3rd, Murphy BR (1994) Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. J Virol 68(8):5321–5325PubMedCentralPubMedGoogle Scholar
  12. Curran J, Boeck R, Kolakofsky D (1991) The Sendai virus P gene expresses both an essential protein and an inhibitor of RNA synthesis by shuffling modules via mRNA editing. EMBO J 10(10):3079–3085PubMedGoogle Scholar
  13. Curran J, Marq JB, Kolakofsky D (1992) The Sendai virus nonstructural C proteins specifically inhibit viral mRNA synthesis. Virology 189(2):647–656PubMedGoogle Scholar
  14. Curran J, Homann H, Buchholz C, Rochat S, Neubert W, Kolakofsky D (1993) The hypervariable C-terminal tail of the Sendai paramyxovirus nucleocapsid protein is required for template function but not for RNA encapsidation. J Virol 67(7):4358–4364PubMedCentralPubMedGoogle Scholar
  15. Curran J, Pelet T, Kolakofsky D (1994) An acidic activation-like domain of the Sendai virus P protein is required for RNA synthesis and encapsidation. Virology 202(2):875–884. doi: 10.1006/viro.1994.1409 PubMedGoogle Scholar
  16. Curran J, Boeck R, Lin-Marq N, Lupas A, Kolakofsky D (1995a) Paramyxovirus phosphoproteins form homotrimers as determined by an epitope dilution assay, via predicted coiled coils. Virology 214(1):139–149. doi: 10.1006/viro.1995.9946 PubMedGoogle Scholar
  17. Curran J, Marq JB, Kolakofsky D (1995b) An N-terminal domain of the Sendai paramyxovirus P protein acts as a chaperone for the NP protein during the nascent chain assembly step of genome replication. J Virol 69(2):849–855PubMedCentralPubMedGoogle Scholar
  18. Cutter D, Mason KW, Howell AP, Fink DL, Green BA, St. Geme JW 3rd (2002) Immunization with Haemophilus influenzae Hap adhesin protects against nasopharyngeal colonization in experimental mice. J Infect Dis 186(8):1115–1121. doi: 10.1086/344233 PubMedGoogle Scholar
  19. de Swart RL, Kuiken T, Timmerman HH, van Amerongen G, Van Den Hoogen BG, Vos HW, Neijens HJ, Andeweg AC, Osterhaus AD (2002) Immunization of macaques with formalin-inactivated respiratory syncytial virus (RSV) induces interleukin-13-associated hypersensitivity to subsequent RSV infection. J Virol 76(22):11561–11569PubMedCentralPubMedGoogle Scholar
  20. de Waal L, Wyatt LS, Yuksel S, van Amerongen G, Moss B, Niesters HG, Osterhaus AD, de Swart RL (2004) Vaccination of infant macaques with a recombinant modified vaccinia virus Ankara expressing the respiratory syncytial virus F and G genes does not predispose for immunopathology. Vaccine 22(8):923–926. doi: 10.1016/j.vaccine.2003.10.010 PubMedGoogle Scholar
  21. Einberger H, Mertz R, Hofschneider PH, Neubert WJ (1990) Purification, renaturation, and reconstituted protein kinase activity of the Sendai virus large (L) protein: L protein phosphorylates the NP and P proteins in vitro. J Virol 64(9):4274–4280PubMedCentralPubMedGoogle Scholar
  22. Falsey AR, Walsh EE (1996) Safety and immunogenicity of a respiratory syncytial virus subunit vaccine (PFP-2) in ambulatory adults over age 60. Vaccine 14(13):1214–1218PubMedGoogle Scholar
  23. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE (2005) Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med 352(17):1749–1759. doi: 10.1056/NEJMoa043951 PubMedGoogle Scholar
  24. Feller JA, Smallwood S, Horikami SM, Moyer SA (2000) Mutations in conserved domains IV and VI of the large (L) subunit of the Sendai virus RNA polymerase give a spectrum of defective RNA synthesis phenotypes. Virology 269(2):426–439. doi: 10.1006/viro.2000.0234 PubMedGoogle Scholar
  25. Fu Y, He J, Zheng X, Wu Q, Zhang M, Wang X, Wang Y, Xie C, Tang Q, Wei W, Wang M, Song J, Qu J, Zhang Y, Wang X, Hong T (2009) Intranasal immunization with a replication-deficient adenoviral vector expressing the fusion glycoprotein of respiratory syncytial virus elicits protective immunity in BALB/c mice. Biochem Biophys Res Commun 381(4):528–532. doi: 10.1016/j.bbrc.2009.02.075 PubMedGoogle Scholar
  26. Garcin D, Latorre P, Kolakofsky D (1999) Sendai virus C proteins counteract the interferon-mediated induction of an antiviral state. J Virol 73(8):6559–6565PubMedCentralPubMedGoogle Scholar
  27. Geall AJ, Verma A, Otten GR, Shaw CA, Hekele A, Banerjee K, Cu Y, Beard CW, Brito LA, Krucker T, O’Hagan DT, Singh M, Mason PW, Valiante NM, Dormitzer PR, Barnett SW, Rappuoli R, Ulmer JB, Mandl CW (2012) Nonviral delivery of self-amplifying RNA vaccines. Proc Natl Acad Sci USA 109(36):14604–14609. doi: 10.1073/pnas.1209367109 PubMedGoogle Scholar
  28. Glenn GM, Smith G, Fries L, Raghunandan R, Lu H, Zhou B, Thomas DN, Hickman SP, Kpamegan E, Boddapati S, Piedra PA (2013) Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine. Vaccine 31(3):524–532. doi: 10.1016/j.vaccine.2012.11.009 PubMedGoogle Scholar
  29. Glezen WP, Taber LH, Frank AL, Kasel JA (1986) Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child 140(6):543–546 (1960)PubMedGoogle Scholar
  30. Gomez M, Mufson MA, Dubovsky F, Knightly C, Zeng W, Losonsky G (2009) Phase-I study MEDI-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children. Pediatr Infect Dis J 28(7):655–658. doi: 10.1097/INF.0b013e318199c3b1 PubMedGoogle Scholar
  31. Gotoh B, Takeuchi K, Komatsu T, Yokoo J, Kimura Y, Kurotani A, Kato A, Nagai Y (1999) Knockout of the Sendai virus C gene eliminates the viral ability to prevent the interferon-alpha/beta-mediated responses. FEBS Lett 459(2):205–210PubMedGoogle Scholar
  32. Griesenbach U, Cassady RL, Ferrari S, Fukumura M, Muller C, Schmitt E, Zhu J, Jeffery PK, Nagai Y, Geddes DM, Hasegawa M, Alton EW (2002) The nasal epithelium as a factory for systemic protein delivery. Mol Ther 5(2):98–103. doi: 10.1006/mthe.2002.0524 PubMedGoogle Scholar
  33. The IMpact-RSV Study Group (1998) Palivizumab, a humanized respiratory syncytial virus monoclonal antibody, reduces hospitalization from respiratory syncytial virus infection in high-risk infants. Pediatrics 102(3 Pt 1):531–537Google Scholar
  34. Hammond DC, Lesnaw JA (1987) Functional analysis of hypomethylation variants of the New Jersey serotype of vesicular stomatitis virus. Virology 160(2):330–335PubMedGoogle Scholar
  35. Hammond DC, Haley BE, Lesnaw JA (1992) Identification and characterization of serine/threonine protein kinase activity intrinsic to the L protein of vesicular stomatitis virus New Jersey. J Gen Virol 73(Pt 1):67–75PubMedGoogle Scholar
  36. Hasan MK, Kato A, Muranaka M, Yamaguchi R, Sakai Y, Hatano I, Tashiro M, Nagai Y (2000) Versatility of the accessory C proteins of Sendai virus: contribution to virus assembly as an additional role. J Virol 74(12):5619–5628PubMedCentralPubMedGoogle Scholar
  37. Heidema J, de Bree GJ, De Graaff PM, van Maren WW, Hoogerhout P, Out TA, Kimpen JL, van Bleek GM (2004) Human CD8(+) T cell responses against five newly identified respiratory syncytial virus-derived epitopes. J Gen Virol 85(Pt 8):2365–2374. doi: 10.1099/vir.0.80131-0 PubMedGoogle Scholar
  38. Hercyk N, Horikami SM, Moyer SA (1988) The vesicular stomatitis virus L protein possesses the mRNA methyltransferase activities. Virology 163(1):222–225PubMedGoogle Scholar
  39. Horikami SM, Curran J, Kolakofsky D, Moyer SA (1992) Complexes of Sendai virus NP-P and P-L proteins are required for defective interfering particle genome replication in vitro. J Virol 66(8):4901–4908PubMedCentralPubMedGoogle Scholar
  40. Horikami SM, Smallwood S, Moyer SA (1996) The Sendai virus V protein interacts with the NP protein to regulate viral genome RNA replication. Virology 222(2):383–390. doi: 10.1006/viro.1996.0435 PubMedGoogle Scholar
  41. Horikami SM, Hector RE, Smallwood S, Moyer SA (1997) The Sendai virus C protein binds the L polymerase protein to inhibit viral RNA synthesis. Virology 235(2):261–270. doi: 10.1006/viro.1997.8702 PubMedGoogle Scholar
  42. Hunt DM, Hutchinson KL (1993) Amino acid changes in the L polymerase protein of vesicular stomatitis virus which confer aberrant polyadenylation and temperature-sensitive phenotypes. Virology 193(2):786–793. doi: 10.1006/viro.1993.1187 PubMedGoogle Scholar
  43. Irie T, Shimazu Y, Yoshida T, Sakaguchi T (2007) The YLDL sequence within Sendai virus M protein is critical for budding of virus-like particles and interacts with Alix/AIP1 independently of C protein. J Virol 81(5):2263–2273. doi: 10.1128/jvi.02218-06 PubMedCentralPubMedGoogle Scholar
  44. Jin H, Elliott RM (1992) Mutagenesis of the L protein encoded by Bunyamwera virus and production of monospecific antibodies. J Gen Virol 73(Pt 9):2235–2244PubMedGoogle Scholar
  45. Jin H, Zhou H, Cheng X, Tang R, Munoz M, Nguyen N (2000) Recombinant respiratory syncytial viruses with deletions in the NS1, NS2, SH, and M2-2 genes are attenuated in vitro and in vivo. Virology 273(1):210–218. doi: 10.1006/viro.2000.0393 PubMedGoogle Scholar
  46. Johnson TR, Graham BS (1999) Secreted respiratory syncytial virus G glycoprotein induces interleukin-5 (IL-5), IL-13, and eosinophilia by an IL-4-independent mechanism. J Virol 73(10):8485–8495PubMedCentralPubMedGoogle Scholar
  47. Kapikian AZ, Mitchell RH, Chanock RM, Shvedoff RA, Stewart CE (1969) An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. Am J Epidemiol 89(4):405–421PubMedGoogle Scholar
  48. Karron RA, Wright PF, Crowe JE Jr, Clements-Mann ML, Thompson J, Makhene M, Casey R, Murphy BR (1997) Evaluation of two live, cold-passaged, temperature-sensitive respiratory syncytial virus vaccines in chimpanzees and in human adults, infants, and children. J Infect Dis 176(6):1428–1436PubMedGoogle Scholar
  49. Karron RA, Wright PF, Belshe RB, Thumar B, Casey R, Newman F, Polack FP, Randolph VB, Deatly A, Hackell J, Gruber W, Murphy BR, Collins PL (2005) Identification of a recombinant live attenuated respiratory syncytial virus vaccine candidate that is highly attenuated in infants. J Infect Dis 191(7):1093–1104. doi: 10.1086/427813 PubMedGoogle Scholar
  50. Kato A, Kiyotani K, Sakai Y, Yoshida T, Nagai Y (1997a) The paramyxovirus, Sendai virus, V protein encodes a luxury function required for viral pathogenesis. EMBO J 16(3):578–587. doi: 10.1093/emboj/16.3.578 PubMedGoogle Scholar
  51. Kato A, Kiyotani K, Sakai Y, Yoshida T, Shioda T, Nagai Y (1997b) Importance of the cysteine-rich carboxyl-terminal half of V protein for Sendai virus pathogenesis. J Virol 71(10):7266–7272PubMedCentralPubMedGoogle Scholar
  52. Kitikoon P, Nilubol D, Erickson BJ, Janke BH, Hoover TC, Sornsen SA, Thacker EL (2006) The immune response and maternal antibody interference to a heterologous H1N1 swine influenza virus infection following vaccination. Vet Immunol Immunopathol 112(3–4):117–128. doi: 10.1016/j.vetimm.2006.02.008 PubMedGoogle Scholar
  53. Lamb RA, Mahy BW, Choppin PW (1976) The synthesis of Sendai virus polypeptides in infected cells. Virology 69(1):116–131PubMedGoogle Scholar
  54. Langley JM, Sales V, McGeer A, Guasparini R, Predy G, Meekison W, Li M, Capellan J, Wang E (2009) A dose-ranging study of a subunit respiratory syncytial virus subtype A vaccine with and without aluminum phosphate adjuvantation in adults > or =65 years of age. Vaccine 27(42):5913–5919. doi: 10.1016/j.vaccine.2009.07.038 PubMedGoogle Scholar
  55. Latorre P, Kolakofsky D, Curran J (1998) Sendai virus Y proteins are initiated by a ribosomal shunt. Mol Cell Biol 18(9):5021–5031PubMedCentralPubMedGoogle Scholar
  56. Levely ME, Bannow CA, Smith CW, Nicholas JA (1991) Immunodominant T-cell epitope on the F protein of respiratory syncytial virus recognized by human lymphocytes. J Virol 65(7):3789–3796PubMedCentralPubMedGoogle Scholar
  57. Mok H, Lee S, Utley TJ, Shepherd BE, Polosukhin VV, Collier ML, Davis NL, Johnston RE, Crowe JE Jr (2007) Venezuelan equine encephalitis virus replicon particles encoding respiratory syncytial virus surface glycoproteins induce protective mucosal responses in mice and cotton rats. J Virol 81(24):13710–13722. doi: 10.1128/jvi.01351-07 PubMedCentralPubMedGoogle Scholar
  58. Moore EC, Barber J, Tripp RA (2008) Respiratory syncytial virus (RSV) attachment and nonstructural proteins modify the type I interferon response associated with suppressor of cytokine signaling (SOCS) proteins and IFN-stimulated gene-15 (ISG15). Virol J 5:116. doi: 10.1186/1743-422x-5-116 PubMedCentralPubMedGoogle Scholar
  59. Moriya C, Horiba S, Inoue M, Iida A, Hara H, Shu T, Hasegawa M, Matano T (2008) Antigen-specific T-cell induction by vaccination with a recombinant Sendai virus vector even in the presence of vector-specific neutralizing antibodies in rhesus macaques. Biochem Biophys Res Commun 371(4):850–854. doi: 10.1016/j.bbrc.2008.04.156 PubMedGoogle Scholar
  60. Moriya C, Horiba S, Kurihara K, Kamada T, Takahara Y, Inoue M, Iida A, Hara H, Shu T, Hasegawa M, Matano T (2011) Intranasal Sendai viral vector vaccination is more immunogenic than intramuscular under pre-existing anti-vector antibodies. Vaccine 29(47):8557–8563. doi: 10.1016/j.vaccine.2011.09.028 PubMedGoogle Scholar
  61. Mottet G, Curran J, Roux L (1990) Intracellular stability of nonreplicating paramyxovirus nucleocapsids. Virology 176(1):1–7PubMedGoogle Scholar
  62. Murawski MR, McGinnes LW, Finberg RW, Kurt-Jones EA, Massare MJ, Smith G, Heaton PM, Fraire AE, Morrison TG (2010) Newcastle disease virus-like particles containing respiratory syncytial virus G protein induced protection in BALB/c mice, with no evidence of immunopathology. J Virol 84(2):1110–1123. doi: 10.1128/jvi.01709-09 PubMedCentralPubMedGoogle Scholar
  63. Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, O’Brien KL, Roca A, Wright PF, Bruce N, Chandran A, Theodoratou E, Sutanto A, Sedyaningsih ER, Ngama M, Munywoki PK, Kartasasmita C, Simoes EA, Rudan I, Weber MW, Campbell H (2010) Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 375(9725):1545–1555. doi: 10.1016/s0140-6736(10)60206-1 PubMedCentralPubMedGoogle Scholar
  64. Olszewska W, Suezer Y, Sutter G, Openshaw PJ (2004) Protective and disease-enhancing immune responses induced by recombinant modified vaccinia Ankara (MVA) expressing respiratory syncytial virus proteins. Vaccine 23(2):215–221. doi: 10.1016/j.vaccine.2004.05.015 PubMedGoogle Scholar
  65. Openshaw PJ, Culley FJ, Olszewska W (2001) Immunopathogenesis of vaccine-enhanced RSV disease. Vaccine 20(suppl 1):S27–S31PubMedGoogle Scholar
  66. Patwardhan S, Gupta KC (1988) Translation initiation potential of the 5′ proximal AUGs of the polycistronic P/C mRNA of Sendai virus. A multipurpose vector for site-specific mutagenesis. J Biol Chem 263(10):4907–4913PubMedGoogle Scholar
  67. Piedra PA, Cron SG, Jewell A, Hamblett N, McBride R, Palacio MA, Ginsberg R, Oermann CM, Hiatt PW (2003) Immunogenicity of a new purified fusion protein vaccine to respiratory syncytial virus: a multi-center trial in children with cystic fibrosis. Vaccine 21(19–20):2448–2460PubMedGoogle Scholar
  68. Poch O, Blumberg BM, Bougueleret L, Tordo N (1990) Sequence comparison of five polymerases (L proteins) of unsegmented negative-strand RNA viruses: theoretical assignment of functional domains. J Gen Virol 71(Pt 5):1153–1162PubMedGoogle Scholar
  69. Power UF, Nguyen TN, Rietveld E, de Swart RL, Groen J, Osterhaus AD, de Groot R, Corvaia N, Beck A, Bouveret-Le-Cam N, Bonnefoy JY (2001) Safety and immunogenicity of a novel recombinant subunit respiratory syncytial virus vaccine (BBG2Na) in healthy young adults. J Infect Dis 184(11):1456–1460. doi: 10.1086/324426 PubMedGoogle Scholar
  70. Pringle CR, Filipiuk AH, Robinson BS, Watt PJ, Higgins P, Tyrrell DA (1993) Immunogenicity and pathogenicity of a triple temperature-sensitive modified respiratory syncytial virus in adult volunteers. Vaccine 11(4):473–478PubMedGoogle Scholar
  71. Quan FS, Kim Y, Lee S, Yi H, Kang SM, Bozja J, Moore ML, Compans RW (2011) Viruslike particle vaccine induces protection against respiratory syncytial virus infection in mice. J Infect Dis 204(7):987–995. doi: 10.1093/infdis/jir474 PubMedGoogle Scholar
  72. Ryan KW, Morgan EM, Portner A (1991) Two noncontiguous regions of Sendai virus P protein combine to form a single nucleocapsid binding domain. Virology 180(1):126–134PubMedGoogle Scholar
  73. Schnell MJ, Conzelmann KK (1995) Polymerase activity of in vitro mutated rabies virus L protein. Virology 214(2):522–530. doi: 10.1006/viro.1995.0063 PubMedGoogle Scholar
  74. Shay DK, Holman RC, Newman RD, Liu LL, Stout JW, Anderson LJ (1999) Bronchiolitis-associated hospitalizations among US children, 1980–1996. JAMA 282(15):1440–1446PubMedGoogle Scholar
  75. Sidhu MS, Menonna JP, Cook SD, Dowling PC, Udem SA (1993) Canine distemper virus L gene: sequence and comparison with related viruses. Virology 193(1):50–65. doi: 10.1006/viro.1993.1102 PubMedGoogle Scholar
  76. Sleat DE, Banerjee AK (1993) Transcriptional activity and mutational analysis of recombinant vesicular stomatitis virus RNA polymerase. J Virol 67(3):1334–1339PubMedCentralPubMedGoogle Scholar
  77. Slobod KS, Shenep JL, Lujan-Zilbermann J, Allison K, Brown B, Scroggs RA, Portner A, Coleclough C, Hurwitz JL (2004) Safety and immunogenicity of intranasal murine parainfluenza virus type 1 (Sendai virus) in healthy human adults. Vaccine 22(23-24):3182–3186. doi: 10.1016/j.vaccine.2004.01.053 PubMedGoogle Scholar
  78. Smallwood S, Ryan KW, Moyer SA (1994) Deletion analysis defines a carboxyl-proximal region of Sendai virus P protein that binds to the polymerase L protein. Virology 202(1):154–163. doi: 10.1006/viro.1994.1331 PubMedGoogle Scholar
  79. Smallwood S, Easson CD, Feller JA, Horikami SM, Moyer SA (1999) Mutations in conserved domain II of the large (L) subunit of the Sendai virus RNA polymerase abolish RNA synthesis. Virology 262(2):375–383. doi: 10.1006/viro.1999.9933 PubMedGoogle Scholar
  80. Smallwood S, Cevik B, Moyer SA (2002a) Intragenic complementation and oligomerization of the L subunit of the Sendai virus RNA polymerase. Virology 304(2):235–245PubMedGoogle Scholar
  81. Smallwood S, Hovel T, Neubert WJ, Moyer SA (2002b) Different substitutions at conserved amino acids in domains II and III in the Sendai L RNA polymerase protein inactivate viral RNA synthesis. Virology 304(1):135–145PubMedGoogle Scholar
  82. Smith G, Raghunandan R, Wu Y, Liu Y, Massare M, Nathan M, Zhou B, Lu H, Boddapati S, Li J, Flyer D, Glenn G (2012) Respiratory syncytial virus fusion glycoprotein expressed in insect cells form protein nanoparticles that induce protective immunity in cotton rats. PLoS One 7(11):e50852. doi: 10.1371/journal.pone.0050852 PubMedCentralPubMedGoogle Scholar
  83. Srikiatkhachorn A, Braciale TJ (1997) Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. J Exp Med 186(3):421–432PubMedCentralPubMedGoogle Scholar
  84. Stegmann T, Kamphuis T, Meijerhof T, Goud E, de Haan A, Wilschut J (2010) Lipopeptide-adjuvanted respiratory syncytial virus virosomes: a safe and immunogenic non-replicating vaccine formulation. Vaccine 28(34):5543–5550. doi: 10.1016/j.vaccine.2010.06.041 PubMedGoogle Scholar
  85. Tapparel C, Hausmann S, Pelet T, Curran J, Kolakofsky D, Roux L (1997) Inhibition of Sendai virus genome replication due to promoter-increased selectivity: a possible role for the accessory C proteins. J Virol 71(12):9588–9599PubMedCentralPubMedGoogle Scholar
  86. Ternette N, Tippler B, Uberla K, Grunwald T (2007) Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus. Vaccine 25(41):7271–7279. doi: 10.1016/j.vaccine.2007.07.025 PubMedGoogle Scholar
  87. van Bleek GM, Poelen MC, van der Most R, Brugghe HF, Timmermans HA, Boog CJ, Hoogerhout P, Otten HG, van Els CA (2003) Identification of immunodominant epitopes derived from the respiratory syncytial virus fusion protein that are recognized by human CD4 T cells. J Virol 77(2):980–988PubMedCentralPubMedGoogle Scholar
  88. Vidal S, Curran J, Kolakofsky D (1990) Editing of the Sendai virus P/C mRNA by G insertion occurs during mRNA synthesis via a virus-encoded activity. J Virol 64(1):239–246PubMedCentralPubMedGoogle Scholar
  89. Voges B, Vallbracht S, Zimmer G, Bossow S, Neubert WJ, Richter K, Hobeika E, Herrler G, Ehl S (2007) Recombinant Sendai virus induces T cell immunity against respiratory syncytial virus that is protective in the absence of antibodies. Cell Immunol 247(2):85–94. doi: 10.1016/j.cellimm.2007.07.005 PubMedGoogle Scholar
  90. Waris ME, Tsou C, Erdman DD, Zaki SR, Anderson LJ (1996) Respiratory synctial virus infection in BALB/c mice previously immunized with formalin-inactivated virus induces enhanced pulmonary inflammatory response with a predominant Th2-like cytokine pattern. J Virol 70(5):2852–2860PubMedCentralPubMedGoogle Scholar
  91. Wiegand MA, Bossow S, Schlecht S, Neubert WJ (2007) De novo synthesis of N and P proteins as a key step in Sendai virus gene expression. J Virol 81(24):13835–13844. doi: 10.1128/jvi.00914-07 PubMedCentralPubMedGoogle Scholar
  92. Wiegand M, Gori-Savellini G, Martorelli B, Bossow S, Neubert WJ, Cusi MG (2013) Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector. Vaccine. doi: 10.1016/j.vaccine.2013.06.053 PubMedGoogle Scholar
  93. Willenbrink W, Neubert WJ (1994) Long-term replication of Sendai virus defective interfering particle nucleocapsids in stable helper cell lines. J Virol 68(12):8413–8417PubMedCentralPubMedGoogle Scholar
  94. Wright PF, Karron RA, Belshe RB, Thompson J, Crowe JE Jr, Boyce TG, Halburnt LL, Reed GW, Whitehead SS, Anderson EL, Wittek AE, Casey R, Eichelberger M, Thumar B, Randolph VB, Udem SA, Chanock RM, Murphy BR (2000) Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy. J Infect Dis 182(5):1331–1342. doi: 10.1086/315859 PubMedGoogle Scholar
  95. Wright PF, Karron RA, Madhi SA, Treanor JJ, King JC, O’Shea A, Ikizler MR, Zhu Y, Collins PL, Cutland C, Randolph VB, Deatly AM, Hackell JG, Gruber WC, Murphy BR (2006) The interferon antagonist NS2 protein of respiratory syncytial virus is an important virulence determinant for humans. J Infect Dis 193(4):573–581. doi: 10.1086/499600 PubMedGoogle Scholar
  96. Wyatt LS, Whitehead SS, Venanzi KA, Murphy BR, Moss B (1999) Priming and boosting immunity to respiratory syncytial virus by recombinant replication-defective vaccinia virus MVA. Vaccine 18(5–6):392–397PubMedGoogle Scholar
  97. Yonemitsu Y, Kitson C, Ferrari S, Farley R, Griesenbach U, Judd D, Steel R, Scheid P, Zhu J, Jeffery PK, Kato A, Hasan MK, Nagai Y, Masaki I, Fukumura M, Hasegawa M, Geddes DM, Alton EW (2000) Efficient gene transfer to airway epithelium using recombinant Sendai virus. Nat Biotechnol 18(9):970–973. doi: 10.1038/79463 PubMedGoogle Scholar
  98. Yu D, Shioda T, Kato A, Hasan MK, Sakai Y, Nagai Y (1997) Sendai virus-based expression of HIV-1 gp120: reinforcement by the V(−) version. Genes Cells 2(7):457–466PubMedGoogle Scholar
  99. Yu JR, Kim S, Lee JB, Chang J (2008) Single intranasal immunization with recombinant adenovirus-based vaccine induces protective immunity against respiratory syncytial virus infection. J Virol 82(5):2350–2357. doi: 10.1128/jvi.02372-07 PubMedCentralPubMedGoogle Scholar
  100. Zhan X, Hurwitz JL, Krishnamurthy S, Takimoto T, Boyd K, Scroggs RA, Surman S, Portner A, Slobod KS (2007) Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B. Vaccine 25(52):8782–8793. doi: 10.1016/j.vaccine.2007.10.038 PubMedCentralPubMedGoogle Scholar
  101. Zhou H, Thompson WW, Viboud CG, Ringholz CM, Cheng PY, Steiner C, Abedi GR, Anderson LJ, Brammer L, Shay DK (2012) Hospitalizations associated with influenza and respiratory syncytial virus in the United States, 1993–2008. Clin Infect Dis 54(10):1427–1436. doi: 10.1093/cid/cis211 PubMedGoogle Scholar

Copyright information

© Springer Japan 2013

Authors and Affiliations

  1. 1.AmVac Research GmbHMartinsriedGermany
  2. 2.Department of Molecular VirologyMax Planck Institute of BiochemistryMartinsriedGermany

Personalised recommendations