Influenza Pathogenesis and Control - Volume II pp 205-235 | Cite as
Design of Alternative Live Attenuated Influenza Virus Vaccines
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Abstract
Each year due to the ever-evolving nature of influenza, new influenza vaccines must be produced to provide protection against the influenza viruses in circulation. Currently, there are two mainstream strategies to generate seasonal influenza vaccines: inactivated and live-attenuated. Inactivated vaccines are non-replicating forms of whole influenza virus, while live-attenuated vaccines are viruses modified to be replication impaired. Although it is widely believed that by inducing both mucosal and humoral immune responses the live-attenuated vaccine provides better protection than that of the inactivated vaccine, there are large populations of individuals who cannot safely receive the LAIV vaccine. Thus, safer LAIV vaccines are needed to provide adequate protection to these populations. Improvement is also needed in the area of vaccine production. Current strategies relying on traditional tissue culture-based and egg-based methods are slow and delay production time. This chapter describes experimental vaccine generation and production strategies that address the deficiencies in current methods for potential human and agricultural use.
Keywords
Influenza Virus Influenza Vaccine Newcastle Disease Virus MDCK Cell Internal Ribosome Entry SiteAbbreviations
- EID50
Egg Infectious Dose 50
- IRES
Internal Ribosome Entry Site
- KO
Knockout
- LAIV
Live-attenuated influenza vaccine
- MDCK
Madin-Darby Canine Kindey Cell
- MLD50
Mouse Lethal Dose 50
- nts
Nucleotides
- Pfu
Plaque Forming Units
- PSI
Packaging Signal
- UTR
Untranslated Region
- RG
Reverse Genetics
- RISC
RNA-induced Silencing Complex
- WT
Wild-Type
References
- Akarsu H, Iwatsuki-Horimoto K, Noda T, Kawakami E, Katsura H, Baudin F, Horimoto T, Kawaoka Y (2011) Structure-based design of NS2 mutants for attenuated influenza A virus vaccines. Virus Res 155:240–248. doi: 10.1016/j.virusres.2010.10.014 PubMedCentralPubMedCrossRefGoogle Scholar
- Alexandrova GI, Maassab HF, Kendal AP, Medvedeva TE, Egorov AY, Klimov AI, Cox NJ (1990) Laboratory properties of cold-adapted influenza B live vaccine strains developed in the US and USSR, and their B/Ann Arbor/1/86 cold-adapted reassortant vaccine candidates. Vaccine 8:61–64PubMedCrossRefGoogle Scholar
- Babai I, Barenholz Y, Zakay-Rones Z, Greenbaum E, Samira S, Hayon I, Rochman M, Kedar E (2001) A novel liposomal influenza vaccine (INFLUSOME-VAC) containing hemagglutinin-neuraminidase and IL-2 or GM-CSF induces protective anti-neuraminidase antibodies cross-reacting with a wide spectrum of influenza A viral strains. Vaccine 20:505–515PubMedCrossRefGoogle Scholar
- Babai I, Samira S, Barenholz Y, Zakay-Rones Z, Kedar E (1999) A novel influenza subunit vaccine composed of liposome-encapsulated haemagglutinin/neuraminidase and IL-2 or GM-CSF. II. Induction of TH1 and TH2 responses in mice. Vaccine 17:1239–1250PubMedCrossRefGoogle Scholar
- Babiuk S, Masic A, Graham J, Neufeld J, van der Loop M, Copps J, Berhane Y, Pasick J, Potter A, Babiuk LA, Weingartl H, Zhou Y (2011) An elastase-dependent attenuated heterologous swine influenza virus protects against pandemic H1N1 2009 influenza challenge in swine. Vaccine 29:3118–3123. doi: 10.1016/j.vaccine.2011.02.069 PubMedCrossRefGoogle Scholar
- Brands R, Visser J, Medema J, Palache AM, van Scharrenburg GJ (1999) Influvac: a safe Madin Darby Canine Kidney (MDCK) cell culture-based influenza vaccine. Dev Biol Stand 98:93–100 (discussion 111)Google Scholar
- Cai Y, Song H, Ye J, Shao H, Padmanabhan R, Sutton TC, Perez DR (2011) Improved hatchability and efficient protection after in ovo vaccination with live-attenuated H7N2 and H9N2 avian influenza viruses. Virol J 8:31. doi: 10.1186/1743-422X-8-31 PubMedCentralPubMedCrossRefGoogle Scholar
- Calvo C, García-García ML, Borrell B, Pozo F, Casas I (2013) Prospective study of influenza C in hospitalized children. Pediatr Infect Dis J 32:916–919. doi: 10.1097/INF.0b013e31828fca10 PubMedGoogle Scholar
- Calvo C, García-García ML, Centeno M, Pérez-Breña P, Casas I (2006) Influenza C virus infection in children, Spain. Emerg Infect Dis 12:1621–1622. doi: 10.3201/eid1210.051170 PubMedCentralPubMedCrossRefGoogle Scholar
- Chambers TM, Quinlivan M, Sturgill T, Cullinane A, Horohov DW, Zamarin D, Arkins S, Garcia-Sastre A, Palese P (2009) Influenza A viruses with truncated NS1 as modified live virus vaccines: pilot studies of safety and efficacy in horses. Equine Vet J 41:87–92PubMedCentralPubMedCrossRefGoogle Scholar
- Chen H, Ye J, Xu K, Angel M, Shao H, Ferrero A, Sutton T, Perez DR (2012) Partial and full PCR-based reverse genetics strategy for influenza viruses. PLoS One 7:e46378PubMedCentralPubMedCrossRefGoogle Scholar
- Cohen M, Zhang XQ, Senaati HP, Chen HW, Varki NM, Schooley RT, Gagneux P (2013) Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase. Virol J 10:321. doi: 10.1186/1743-422X-10-321 PubMedCentralPubMedCrossRefGoogle Scholar
- de Wit E, Spronken MI, Vervaet G, Rimmelzwaan GF, Osterhaus AD, Fouchier RA (2007) A reverse-genetics system for influenza A virus using T7 RNA polymerase. J Gen Virol 88:1281–1287PubMedCrossRefGoogle Scholar
- DeBorde DC, Donabedian AM, Herlocher ML, Naeve CW, Maassab HF (1988) Sequence comparison of wild-type and cold-adapted B/Ann Arbor/1/66 influenza virus genes. Virology 163:429–443PubMedCrossRefGoogle Scholar
- DeBorde DC, Naeve CW, Herlocher ML, Maassab HF (1987) Nucleotide sequences of the PA and PB1 genes of B/Ann Arbor/1/66 virus: comparison with genes of B/Lee/40 and type A influenza viruses. Virus Res 8:33–41PubMedCrossRefGoogle Scholar
- Donelan NR, Dauber B, Wang X, Basler CF, Wolff T, García-Sastre A (2004) The N- and C-terminal domains of the NS1 protein of influenza B virus can independently inhibit IRF-3 and beta interferon promoter activation. J Virol 78:11574–11582. doi: 10.1128/JVI.78.21.11574-11582.2004 PubMedCentralPubMedCrossRefGoogle Scholar
- Dormitzer PR, Suphaphiphat P, Gibson DG, Wentworth DE, Stockwell TB, Algire MA, Alperovich N, Barro M, Brown DM, Craig S, Dattilo BM, Denisova EA, De Souza I, Eickmann M, Dugan VG, Ferrari A, Gomila RC, Han L, Judge C, Mane S, Matrosovich M, Merryman C, Palladino G, Palmer GA, Spencer T, Strecker T, Trusheim H, Uhlendorff J, Wen Y, Yee AC, Zaveri J, Zhou B, Becker S, Donabedian A, Mason PW, Glass JI, Rappuoli R, Venter JC (2013) Synthetic generation of influenza vaccine viruses for rapid response to pandemics. Sci Transl Med 5:185ra68Google Scholar
- Dos Santos Afonso E, Escriou N, Leclercq I, van der Werf S, Naffakh N (2005) The generation of recombinant influenza A viruses expressing a PB2 fusion protein requires the conservation of a packaging signal overlapping the coding and noncoding regions at the 5’ end of the PB2 segment. Virology 341:34–46CrossRefGoogle Scholar
- Ferko B, Stasakova J, Sereinig S, Romanova J, Katinger D, Niebler B, Katinger H, Egorov A (2001) Hyperattenuated recombinant influenza A virus nonstructural-protein-encoding vectors induce human immunodeficiency virus type 1 Nef-specific systemic and mucosal immune responses in mice. J Virol 75:8899–8908PubMedCentralPubMedCrossRefGoogle Scholar
- Flick R, Hobom G (1999) Transient bicistronic vRNA segments for indirect selection of recombinant influenza viruses. Virology 262:93–103PubMedCrossRefGoogle Scholar
- Fodor E, Devenish L, Engelhardt OG, Palese P, Brownlee GG, Garcia-Sastre A (1999) Rescue of influenza A virus from recombinant DNA. J Virol 73:9679–9682PubMedCentralPubMedGoogle Scholar
- Fujii K, Fujii Y, Noda T, Muramoto Y, Watanabe T, Takada A, Goto H, Horimoto T, Kawaoka Y (2005) Importance of both the coding and the segment-specific noncoding regions of the influenza A virus NS segment for its efficient incorporation into virions. J Virol 79:3766–3774PubMedCentralPubMedCrossRefGoogle Scholar
- Fukuyama S, Kawaoka Y (2011) The pathogenesis of influenza virus infections: the contributions of virus and host factors. Curr Opin Immunol 23:481–486. doi: 10.1016/j.coi.2011.07.016 PubMedCentralPubMedCrossRefGoogle Scholar
- Gao Q, Lowen AC, Wang TT, Palese P (2010) A nine-segment influenza a virus carrying subtype H1 and H3 hemagglutinins. J Virol 84:8062–8071PubMedCentralPubMedCrossRefGoogle Scholar
- Gao Q, Palese P (2009) Rewiring the RNAs of influenza virus to prevent reassortment. Proc Natl Acad Sci USA 106:15891–15896PubMedCentralPubMedCrossRefGoogle Scholar
- Garcia-Sastre A, Muster T, Barclay WS, Percy N, Palese P (1994a) Use of a mammalian internal ribosomal entry site element for expression of a foreign protein by a transfectant influenza virus. J Virol 68:6254–6261PubMedCentralPubMedGoogle Scholar
- Garcia-Sastre A, Percy N, Barclay W, Palese P (1994b) Introduction of foreign sequences into the genome of influenza A virus. Dev Biol Stand 82:237–246PubMedGoogle Scholar
- Ghate AA, Air GM (1999) Influenza type B neuraminidase can replace the function of type A neuraminidase. Virology 264:265–277PubMedCrossRefGoogle Scholar
- Goto H, Muramoto Y, Noda T, Kawaoka Y (2013) The genome-packaging signal of the influenza A virus genome comprises a genome incorporation signal and a genome-bundling signal. J Virol 87:11316–11322. doi: 10.1128/JVI.01301-13 PubMedCentralPubMedCrossRefGoogle Scholar
- Hai R, Garcia-Sastre A, Swayne DE, Palese P (2011) A reassortment-incompetent live attenuated influenza virus vaccine for protection against pandemic virus strains. J Virol 85:6832–6843PubMedCentralPubMedCrossRefGoogle Scholar
- Hatta Y, Hatta M, Bilsel P, Neumann G, Kawaoka Y (2011) An M2 cytoplasmic tail mutant as a live attenuated influenza vaccine against pandemic (H1N1) 2009 influenza virus. Vaccine 29:2308–2312. doi: 10.1016/j.vaccine.2011.01.023 PubMedCentralPubMedCrossRefGoogle Scholar
- Heaton NS, Leyva-Grado VH, Tan GS, Eggink D, Hai R, Palese P (2013) In vivo bioluminescent imaging of influenza a virus infection and characterization of novel cross-protective monoclonal antibodies. J Virol 87:8272–8281PubMedCentralPubMedCrossRefGoogle Scholar
- Heix J, Grummt I (1995) Species specificity of transcription by RNA polymerase I. Curr Opin Genet Dev 5:652–656PubMedCrossRefGoogle Scholar
- Henke A, Rohland N, Zell R, Wutzler P (2006) Co-expression of interleukin-2 by a bicistronic plasmid increases the efficacy of DNA immunization to prevent influenza virus infections. Intervirology 49:249–252. doi: 10.1159/000092487 PubMedCrossRefGoogle Scholar
- Hickman D, Hossain MJ, Song H, Araya Y, Solórzano A, Perez DR (2008) An avian live attenuated master backbone for potential use in epidemic and pandemic influenza vaccines. J Gen Virol 89:2682–2690. doi: 10.1099/vir.0.2008/004143-0 PubMedCentralPubMedCrossRefGoogle Scholar
- Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG (2000) A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci USA 97:6108–6113PubMedCentralPubMedCrossRefGoogle Scholar
- Hutchinson EC, von Kirchbach JC, Gog JR, Digard P (2010) Genome packaging in influenza A virus. J Gen Virol 91:313–328. doi: 10.1099/vir.0.017608-0 PubMedCrossRefGoogle Scholar
- Kadota J (2013) Emergence of a new strain of the avian influenza A (H7N9) virus. Respir Investig 51:49. doi: 10.1016/j.resinv.2013.05.001 PubMedCrossRefGoogle Scholar
- Kaverin NV, Varich NL, Sklyanskaya EI, Amvrosieva TV, Petrik J, Vovk TC (1983) Studies on heterotypic interference between influenza A and B viruses: a differential inhibition of the synthesis of viral proteins and RNAs. J Gen Virol 64(Pt 10):2139–2146PubMedCrossRefGoogle Scholar
- Kistner O, Barrett PN, Mundt W, Reiter M, Schober-Bendixen S, Dorner F (1998) Development of a mammalian cell (Vero) derived candidate influenza virus vaccine. Vaccine 16:960–968PubMedCrossRefGoogle Scholar
- Kistner O, Barrett PN, Mundt W, Reiter M, Schober-Bendixen S, Eder G, Dorner F (1999) Development of a vero cell-derived influenza whole virus vaccine. Dev Biol Stand 98:101–110 (discussion 111)Google Scholar
- Kittel C, Ferko B, Kurz M, Voglauer R, Sereinig S, Romanova J, Stiegler G, Katinger H, Egorov A (2005) Generation of an influenza A virus vector expressing biologically active human interleukin-2 from the NS gene segment. J Virol 79:10672–10677PubMedCentralPubMedCrossRefGoogle Scholar
- Kittel C, Sereinig S, Ferko B, Stasakova J, Romanova J, Wolkerstorfer A, Katinger H, Egorov A (2004) Rescue of influenza virus expressing GFP from the NS1 reading frame. Virology 324:67–73PubMedCrossRefGoogle Scholar
- Langlois RA, Albrecht RA, Kimble B, Sutton T, Shapiro JS, Finch C, Angel M, Chua MA, Gonzalez-Reiche AS, Xu K, Perez D, García-Sastre A, Tenoever BR (2013) MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies. Nat Biotechnol. doi: 10.1038/nbt.2666 PubMedCentralPubMedGoogle Scholar
- Leibler JH, Otte J, Roland-Holst D, Pfeiffer DU, Soares Magalhaes R, Rushton J, Graham JP, Silbergeld EK (2009) Industrial food animal production and global health risks: exploring the ecosystems and economics of avian influenza. Ecohealth 6:58–70. doi: 10.1007/s10393-009-0226-0 PubMedCrossRefGoogle Scholar
- Li F, Feng L, Pan W, Dong Z, Li C, Sun C, Chen L (2010) Generation of replication-competent recombinant influenza A viruses carrying a reporter gene harbored in the neuraminidase segment. J Virol 84:12075–12081PubMedCentralPubMedCrossRefGoogle Scholar
- Liang Y, Huang T, Ly H, Parslow TG (2008) Mutational analyses of packaging signals in influenza virus PA, PB1, and PB2 genomic RNA segments. J Virol 82:229–236PubMedCentralPubMedCrossRefGoogle Scholar
- Loving CL, Lager KM, Vincent AL, Brockmeier SL, Gauger PC, Anderson TK, Kitikoon P, Perez DR, Kehrli ME Jr (2013) Efficacy in pigs of inactivated and live attenuated influenza virus vaccines against infection and transmission of an emerging H3N2 similar to the 2011–2012 H3N2v. J Virol 87:9895–9903. doi: 10.1128/JVI.01038-13 PubMedCentralPubMedCrossRefGoogle Scholar
- Loving CL, Vincent AL, Pena L, Perez DR (2012) Heightened adaptive immune responses following vaccination with a temperature-sensitive, live-attenuated influenza virus compared to adjuvanted, whole-inactivated virus in pigs. Vaccine 30:5830–5838. doi: 10.1016/j.vaccine.2012.07.033 PubMedCentralPubMedCrossRefGoogle Scholar
- Maassab HF (1967) Adaptation and growth characteristics of influenza virus at 25 °C. Nature 213:612–614PubMedCrossRefGoogle Scholar
- Maassab HF, Bryant ML (1999) The development of live attenuated cold-adapted influenza virus vaccine for humans. Rev Med Virol 9:237–244PubMedCrossRefGoogle Scholar
- Maassab HF, Francis T, Davenport FM, Hennessy AV, Minuse E, Anderson G (1969) Laboratory and clinical characteristics of attenuated strains of influenza virus. Bull World Health Organ 41:589–594PubMedCentralPubMedGoogle Scholar
- Machado AV, Naffakh N, van der Werf S, Escriou N (2003) Expression of a foreign gene by stable recombinant influenza viruses harboring a dicistronic genomic segment with an internal promoter. Virology 313:235–249PubMedCrossRefGoogle Scholar
- Manicassamy B, Manicassamy S, Belicha-Villanueva A, Pisanelli G, Pulendran B, Garcia-Sastre A (2010) Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus. Proc Natl Acad Sci USA 107:11531–11536PubMedCentralPubMedCrossRefGoogle Scholar
- Marsh GA, Hatami R, Palese P (2007) Specific residues of the influenza A virus hemagglutinin viral RNA are important for efficient packaging into budding virions. J Virol 81:9727–9736PubMedCentralPubMedCrossRefGoogle Scholar
- Masic A, Babiuk LA, Zhou Y (2009a) Reverse genetics-generated elastase-dependent swine influenza viruses are attenuated in pigs. J Gen Virol 90:375–385. doi: 10.1099/vir.0.005447-0 PubMedCrossRefGoogle Scholar
- Masic A, Booth JS, Mutwiri GK, Babiuk LA, Zhou Y (2009b) Elastase-dependent live attenuated swine influenza A viruses are immunogenic and confer protection against swine influenza A virus infection in pigs. J Virol 83:10198–10210. doi: 10.1128/JVI.00926-09 PubMedCentralPubMedCrossRefGoogle Scholar
- Masic A, Lu X, Li J, Mutwiri GK, Babiuk LA, Brown EG, Zhou Y (2010) Immunogenicity and protective efficacy of an elastase-dependent live attenuated swine influenza virus vaccine administered intranasally in pigs. Vaccine 28:7098–7108. doi: 10.1016/j.vaccine.2010.08.003 PubMedCrossRefGoogle Scholar
- Massin P, Rodrigues P, Marasescu M, van der Werf S, Naffakh N (2005) Cloning of the chicken RNA polymerase I promoter and use for reverse genetics of influenza A viruses in avian cells. J Virol 79:13811–13816PubMedCentralPubMedCrossRefGoogle Scholar
- Mbawuike IN, Wyde PR, Anderson PM (1990) Enhancement of the protective efficacy of inactivated influenza A virus vaccine in aged mice by IL-2 liposomes. Vaccine 8:347–352PubMedCrossRefGoogle Scholar
- Monto AS, Maassab HF (1977) Use of influenza vaccine in non-high risk populations. Dev Biol Stand 39:329–335PubMedGoogle Scholar
- Morokutti A, Muster T, Ferko B (2014) Intranasal vaccination with a replication-deficient influenza virus induces heterosubtypic neutralising mucosal IgA antibodies in humans. Vaccine. doi: 10.1016/j.vaccine.2014.02.009 PubMedGoogle Scholar
- Murakami S, Horimoto T, Yamada S, Kakugawa S, Goto H, Kawaoka Y (2008) Establishment of canine RNA polymerase I-driven reverse genetics for influenza A virus: its application for H5N1 vaccine production. J Virol 82:1605–1609PubMedCentralPubMedCrossRefGoogle Scholar
- Muramoto Y, Takada A, Fujii K, Noda T, Iwatsuki-Horimoto K, Watanabe S, Horimoto T, Kida H, Kawaoka Y (2006) Hierarchy among viral RNA (vRNA) segments in their role in vRNA incorporation into influenza A virions. J Virol 80:2318–2325PubMedCentralPubMedCrossRefGoogle Scholar
- Neumann G, Fujii K, Kino Y, Kawaoka Y (2005) An improved reverse genetics system for influenza A virus generation and its implications for vaccine production. Proc Natl Acad Sci USA 102:16825–16829PubMedCentralPubMedCrossRefGoogle Scholar
- Neumann G, Watanabe T, Ito H, Watanabe S, Goto H, Gao P, Hughes M, Perez DR, Donis R, Hoffmann E, Hobom G, Kawaoka Y (1999) Generation of influenza A viruses entirely from cloned cDNAs. Proc Nat Acad Sci USA 96:9345–9350PubMedCentralPubMedCrossRefGoogle Scholar
- Ozawa M, Goto H, Horimoto T, Kawaoka Y (2007) An adenovirus vector-mediated reverse genetics system for influenza A virus generation. J Virol 81:9556–9559PubMedCentralPubMedCrossRefGoogle Scholar
- Palache AM, Scheepers HS, de Regt V, van Ewijk P, Baljet M, Brands R, van Scharrenburg GJ (1999) Safety, reactogenicity and immunogenicity of Madin Darby Canine Kidney cell-derived inactivated influenza subunit vaccine. A meta-analysis of clinical studies. Dev Biol Stand 98:115–125 (discussion 133–4)Google Scholar
- Palese P, Shaw ML (2007) Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields virology, vol 2, 5th edn. Philadelphia, Lippincott Williams and Wilkins, pp 1647–1689Google Scholar
- Park MS, Steel J, Garcia-Sastre A, Swayne D, Palese P (2006) Engineered viral vaccine constructs with dual specificity: avian influenza and Newcastle disease. Proc Natl Acad Sci USA 103:8203–8208. doi: 10.1073/pnas.0602566103 PubMedCentralPubMedCrossRefGoogle Scholar
- Pena L, Sutton T, Chockalingam A, Kumar S, Angel M, Shao H, Chen H, Li W, Perez DR (2013) Influenza viruses with rearranged genomes as live-attenuated vaccines. J Virol 87:5118–5127PubMedCentralPubMedCrossRefGoogle Scholar
- Pena L, Vincent AL, Ye J, Ciacci-Zanella JR, Angel M, Lorusso A, Gauger PC, Janke BH, Loving CL, Perez DR (2011) Modifications in the polymerase genes of a swine-like triple-reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 viruses. J Virol 85:456–469. doi: 10.1128/JVI.01503-10 PubMedCentralPubMedCrossRefGoogle Scholar
- Percy N, Barclay WS, Garcia-Sastre A, Palese P (1994) Expression of a foreign protein by influenza A virus. J Virol 68:4486–4492PubMedCentralPubMedGoogle Scholar
- Perez JT, Pham AM, Lorini MH, Chua MA, Steel J, tenOever BR (2009) MicroRNA-mediated species-specific attenuation of influenza A virus. Nat Biotechnol 27:572–576. doi: 10.1038/nbt.1542 PubMedCrossRefGoogle Scholar
- Pica N, Langlois RA, Krammer F, Margine I, Palese P (2012) NS1-truncated live attenuated virus vaccine provides robust protection to aged mice from viral challenge. J Virol 86:10293–10301. doi: 10.1128/JVI.01131-12 PubMedCentralPubMedCrossRefGoogle Scholar
- Schnitzler SU, Schnitzler P (2009) An update on swine-origin influenza virus A/H1N1: a review. Virus Genes 39:279–292. doi: 10.1007/s11262-009-0404-8 PubMedCrossRefGoogle Scholar
- Sereinig S, Stukova M, Zabolotnyh N, Ferko B, Kittel C, Romanova J, Vinogradova T, Katinger H, Kiselev O, Egorov A (2006) Influenza virus NS vectors expressing the mycobacterium tuberculosis ESAT-6 protein induce CD4+ Th1 immune response and protect animals against tuberculosis challenge. Clin Vaccine Immunol 13:898–904PubMedCentralPubMedCrossRefGoogle Scholar
- Shinya K, Fujii Y, Ito H, Ito T, Kawaoka Y (2004) Characterization of a neuraminidase-deficient influenza a virus as a potential gene delivery vector and a live vaccine. J Virol 78:3083–3088PubMedCentralPubMedCrossRefGoogle Scholar
- Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69:531–569. doi: 10.1146/annurev.biochem.69.1.531 PubMedCrossRefGoogle Scholar
- Snyder MH, Betts RF, DeBorde D, Tierney EL, Clements ML, Herrington D, Sears SD, Dolin R, Maassab HF, Murphy BR (1988) Four viral genes independently contribute to attenuation of live influenza A/Ann Arbor/6/60 (H2N2) cold-adapted reassortant virus vaccines. J Virol 62:488–495PubMedCentralPubMedGoogle Scholar
- Solórzano A, Webby RJ, Lager KM, Janke BH, García-Sastre A, Richt JA (2005) Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. J Virol 79:7535–7543. doi: 10.1128/JVI.79.12.7535-7543.2005 PubMedCentralPubMedCrossRefGoogle Scholar
- Solórzano A, Ye J, Pérez DR (2010) Alternative live-attenuated influenza vaccines based on modifications in the polymerase genes protect against epidemic and pandemic flu. J Virol 84:4587–4596. doi: 10.1128/JVI.00101-10 PubMedCentralPubMedCrossRefGoogle Scholar
- Song H, Nieto GR, Perez DR (2007) A new generation of modified live-attenuated avian influenza viruses using a two-strategy combination as potential vaccine candidates. J Virol 81:9238–9248. doi: 10.1128/JVI.00893-07
- Song MS, Baek YH, Pascua PN, Kwon HI, Park SJ, Kim EH, Lim GJ, Choi YK (2013) Establishment of Vero cell RNA polymerase I-driven reverse genetics for Influenza A virus and its application for pandemic (H1N1) 2009 influenza virus vaccine production. J Gen Virol 94:1230–1235PubMedCrossRefGoogle Scholar
- Stech J, Garn H, Herwig A, Stech O, Dauber B, Wolff T, Mettenleiter TC, Klenk HD (2011) Influenza B virus with modified hemagglutinin cleavage site as a novel attenuated live vaccine. J Infect Dis 204:1483–1490. doi: 10.1093/infdis/jir613
- Stech J, Garn H, Wegmann M, Wagner R, Klenk HD (2005) A new approach to an influenza live vaccine: modification of the cleavage site of hemagglutinin. Nat Med 11:683–689. doi: 10.1038/nm1256 PubMedCrossRefGoogle Scholar
- Steel J, Burmakina SV, Thomas C, Spackman E, Garcia-Sastre A, Swayne DE, Palese P (2008) A combination in-ovo vaccine for avian influenza virus and Newcastle disease virus. Vaccine 26:522–531. doi: 10.1016/j.vaccine.2007.11.032 PubMedCentralPubMedCrossRefGoogle Scholar
- Steel J, Lowen AC, Pena L, Angel M, Solórzano A, Albrecht R, Perez DR, García-Sastre A, Palese P (2009) Live attenuated influenza viruses containing NS1 truncations as vaccine candidates against H5N1 highly pathogenic avian influenza. J Virol 83:1742–1753. doi: 10.1128/JVI.01920-08 PubMedCentralPubMedCrossRefGoogle Scholar
- Tanaka T, Urabe M, Goto H, Tobita K (1984) Isolation and preliminary characterization of a highly cytolytic influenza B virus variant with an aberrant NS gene. Virology 135:515–523PubMedCrossRefGoogle Scholar
- Taubenberger JK, Kash JC (2010) Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 7:440–451. doi: 10.1016/j.chom.2010.05.009 PubMedCentralPubMedCrossRefGoogle Scholar
- tenOever BR (2013) RNA viruses and the host microRNA machinery. Nat Rev Microbiol 11:169–180. doi: 10.1038/nrmicro2971 PubMedCrossRefGoogle Scholar
- Verity EE, Camuglia S, Agius CT, Ong C, Shaw R, Barr I, Middleton D, Rockman S (2011) Rapid generation of pandemic influenza virus vaccine candidate strains using synthetic DNA. Influenza Other Respi Viruses 6:101–109CrossRefGoogle Scholar
- Victor ST, Watanabe S, Katsura H, Ozawa M, Kawaoka Y (2012) A replication-incompetent PB2-knockout influenza A virus vaccine vector. J Virol 86:4123–4128. doi: 10.1128/JVI.06232-11 PubMedCentralPubMedCrossRefGoogle Scholar
- Vieira Machado A, Naffakh N, Gerbaud S, van der Werf S, Escriou N (2006) Recombinant influenza A viruses harboring optimized dicistronic NA segment with an extended native 5’ terminal sequence: induction of heterospecific B and T cell responses in mice. Virology 345:73–87. doi: 10.1016/j.virol.2005.09.050 PubMedCrossRefGoogle Scholar
- Wacheck V, Egorov A, Groiss F, Pfeiffer A, Fuereder T, Hoeflmayer D, Kundi M, Popow-Kraupp T, Redlberger-Fritz M, Mueller CA, Cinatl J, Michaelis M, Geiler J, Bergmann M, Romanova J, Roethl E, Morokutti A, Wolschek M, Ferko B, Seipelt J, Dick-Gudenus R, Muster T (2010) A novel type of influenza vaccine: safety and immunogenicity of replication-deficient influenza virus created by deletion of the interferon antagonist NS1. J Infect Dis 201:354–362. doi: 10.1086/649428 PubMedCrossRefGoogle Scholar
- Wang Z, Duke GM (2007) Cloning of the canine RNA polymerase I promoter and establishment of reverse genetics for influenza A and B in MDCK cells. Virol J 4:102PubMedCentralPubMedCrossRefGoogle Scholar
- Watanabe S, Imai M, Ohara Y, Odagiri T (2003) Influenza B virus BM2 protein is transported through the trans-Golgi network as an integral membrane protein. J Virol 77:10630–10637PubMedCentralPubMedCrossRefGoogle Scholar
- Watanabe S, Watanabe T, Kawaoka Y (2009) Influenza A virus lacking M2 protein as a live attenuated vaccine. J Virol 83:5947–5950. doi: 10.1128/JVI.00450-09 PubMedCentralPubMedCrossRefGoogle Scholar
- Watanabe T, Watanabe S, Kim JH, Hatta M, Kawaoka Y (2008) Novel approach to the development of effective H5N1 influenza A virus vaccines: use of M2 cytoplasmic tail mutants. J Virol 82:2486–2492. doi: 10.1128/JVI.01899-07 PubMedCentralPubMedCrossRefGoogle Scholar
- Wolschek M, Samm E, Seper H, Sturlan S, Kuznetsova I, Schwager C, Khassidov A, Kittel C, Muster T, Egorov A, Bergmann M (2011) Establishment of a chimeric, replication-deficient influenza A virus vector by modulation of splicing efficiency. J Virol 85:2469–2473PubMedCentralPubMedCrossRefGoogle Scholar
- Wood JM, Robertson JS (2004) From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza. Nat Rev Microbiol 2:842–847PubMedCrossRefGoogle Scholar
- Wressnigg N, Shurygina AP, Wolff T, Redlberger-Fritz M, Popow-Kraupp T, Muster T, Egorov A, Kittel C (2009) Influenza B mutant viruses with truncated NS1 proteins grow efficiently in vero cells and are immunogenic in mice. J Gen Virol 90:366–374. doi: 10.1099/vir.0.006122-0 PubMedCrossRefGoogle Scholar
- Wu R, Guan Y, Yang Z, Chen J, Wang H, Chen Q, Sui Z, Fang F, Chen Z (2010) A live bivalent influenza vaccine based on a H9N2 virus strain. Vaccine 28:673–680PubMedCrossRefGoogle Scholar
- Zhang X, Kong W, Ashraf S, Curtiss R 3rd (2009) A one-plasmid system to generate influenza virus in cultured chicken cells for potential use in influenza vaccine. J Virol 83:9296–9303PubMedCentralPubMedCrossRefGoogle Scholar