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2014 | 61 | 3 | 515-522
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DNA vaccines against influenza

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Genetic vaccine technology has been considerably developed within the last two decades. This cost effective and promising strategy can be applied for therapy of cancers and for curing allergy, chronic and infectious diseases, such as a seasonal and pandemic influenza. Despite numerous advantages, several limitations of this technology reduce its performance and can retard its commercial exploitation in humans and its veterinary applications. Inefficient delivery of the DNA vaccine into cells of immunized individuals results in low intracellular supply of suitable expression cassettes encoding an antigen, in its low expression level and, in turn, in reduced immune responses against the antigen. Improvement of DNA delivery into the host cells might significantly increase effectiveness of the DNA vaccine. A vast array of innovative methods and various experimental strategies have been applied in order to enhance the effectiveness of DNA vaccines. They include various strategies improving DNA delivery as well as expression and immunogenic potential of the proteins encoded by the DNA vaccines. Researchers focusing on DNA vaccines against influenza have applied many of these strategies. Recent examples of the most successful modern approaches are discussed in this review.
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  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
  • Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland
  • Ault A, Zajac AM, Kong WP, Gorres JP, Royals M, Wei CJ, Bao S, Yang ZY, Reedy SE, Sturgill TL, Page AE, Donofrio-Newman J, Adams AA, Balasuriya UB, Horohov DW, Chambers TM, Nabel GJ, Rao SS (2012) Immunogenicity and clinical protection against equine influenza by DNA vaccination of ponies. Vaccine 30: 3965-3974.
  • Capua I, Cattoli G (2013) Prevention and control of highly pathogenic avian influenza with particular reference to H5N1. Virus Res 178: 114-120.
  • Chen MW, Liao HY, Huang YX, Jan JT, Huang CC, Ren CT, Wu CY, Cheng TJ, Ho DD, Wong CH (2011) Broadly neutralizing DNA vaccine with specific mutation alters the antigenicity and sugar-binding activities of influenza hemagglutinin. Proc Natl Acad Sci USA 108: 3510-3515.
  • Chen Q, Zhu G, Wang R, Zhang J, He G (2013) Adjuvant effect of CD40 on H5N1 DNA vaccine in mice. Arch Virol 159: 1359-1364.
  • EMEA (2001) Note for Guidance on the Quality, Preclinical and Clinical Aspects of Gene Transfer Medicinal Products. CPMP/BWP/3088/99. available on line:
  • FDA (2007) Guidance for Industry: Considerations for Plasmid DNA Vaccines for Infectious Disease Indications. available on line:
  • Ferraro B, Morrow MP, Hutnick NA, Shin TH, Lucke CE, Weiner DB (2011) Clinical applications of DNA vaccines: current progress. Clin Infect Dis 53: 296-302.
  • Fynan EF, Webster RG, Fuller DH, Haynes JR, Santoro JC, Robinson HL (1993) DNA vaccines: protective immunizations by parenteral, mucosal, and gene-gun inoculations. Proc Natl Acad Sci USA 90: 11478-11482.
  • Gao Y, Wen Z, Dong K, Zhong G, Wang X, Bu Z, Chen H, Ye L, Yang C (2012) Characterization of immune responses induced by immunization with the HA DNA vaccines of two antigenically distinctive H5N1 HPAIV isolates. PLoS One 7: e41332.
  • Girard MP, Tam JS, Pervikov Y, Katz JM (2013) Report on the first WHO integrated meeting on development and clinical trials of influenza vaccines that induce broadly protective and long-lasting immune responses: Hong Kong SAR, China, 24-26 January 2013. Vaccine 31: 3766-3771.
  • Gorres JP, Lager KM, Kong WP, Royals M, Todd JP, Vincent AL, Wei CJ, Loving CL, Zanella EL, Janke B, Kehrli ME, Nabel GJ, Rao SS (2011) DNA vaccination elicits protective immune responses against pandemic and classic swine influenza viruses in pigs. Clin Vaccine Immunol 18: 1987-1995.
  • Horimoto T, Kawaoka Y (2006) Strategies for developing vaccines against H5N1 influenza A viruses. Trends Mol Med 12: 506-514.
  • Iurescia S, Fioretti D, Rinaldi M (2014) Strategies for improving DNA vaccine performance. Methods Mol Biol 1143: 21-31.
  • Jalilian B, Omar AR, Bejo MH, Alitheen NB, Rasoli M, Matsumoto S (2010) Development of avian influenza virus H5 DNA vaccine and MDP-1 gene of Mycobacterium bovis as genetic adjuvant. Genetic Vaccines Therapy 8: 4.
  • Jazayeri SD, Ideris A, Zakaria Z, Shameli K, Moeini H, Omar AR (2012) Cytotoxicity and immunological responses following oral vaccination of nanoencapsulated avian influenza virus H5 DNA vaccine with green synthesis silver nanoparticles. Journal of Controlled Release: Official Journal of the Controlled Release Society 161: 116-123.
  • Khan KH (2013) DNA vaccines: roles against diseases. Germs 3: 26-35.
  • Kim YC, Song JM, Lipatov AS, Choi SO, Lee JW, Donis RO, Compans RW, Kang SM, Prausnitz MR (2012) Increased immunogenicity of avian influenza DNA vaccine delivered to the skin using a microneedle patch. Eur J Pharm Biopharm 81: 239-247.
  • Klinman DM, Klaschik S, Tross D, Shirota H, Steinhagen F (2010) FDA guidance on prophylactic DNA vaccines: analysis and recommendations. Vaccine 28: 2801-2805.
  • Kreijtz JH, Osterhaus AD, Rimmelzwaan GF (2009) Vaccination strategies and vaccine formulations for epidemic and pandemic influenza control. Hum Vaccin 5: 126-135.
  • Kutzler MA, Weiner DB (2008) DNA vaccines: ready for prime time? Nat Rev Genet 9: 776-788.
  • Ledgerwood JE, Wei CJ, Hu Z, Gordon IJ, Enama ME, Hendel CS, McTamney PM, Pearce MB, Yassine HM, Boyington JC, Bailer R, Tumpey TM, Koup RA, Mascola JR, Nabel GJ, Graham BS, Team VS (2011) DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials. Lancet Infect Dis 11: 916-924.
  • Li JP, Jiang YP, Zhao SC, Chang XF, Liu JX, Zeng XY, Li YB, Chen HL (2012a) Protective Efficacy of an H5N1 DNA Vaccine Against Challenge with a Lethal H5N1 Virus in Quail. Avian Diseases 56: 937-939.
  • Li L, Saade F, Petrovsky N (2012b) The future of human DNA vaccines. J Biotechnol 162: 171-182.
  • Lim KL, Jazayeri SD, Yeap SK, Alitheen NB, Bejo MH, Ideris A, Omar AR (2012) Co-administration of avian influenza virus H5 plasmid DNA with chicken IL-15 and IL-18 enhanced chickens immune responses. BMC Vet Res 8: 132.
  • Lim KL, Jazayeri SD, Yeap SK, Mohamed Alitheen NB, Bejo MH, Ideris A, Omar AR (2013) Antibody and T cell responses induced in chickens immunized with avian influenza virus N1 and NP DNA vaccine with chicken IL-15 and IL-18. Res Vet Sci 95: 1224-1234.
  • Lin SC, Lin YF, Chong P, Wu SC (2012) Broader neutralizing antibodies against H5N1 viruses using prime-boost immunization of hyperglycosylated hemagglutinin DNA and virus-like particles. PloS one 7: e39075.
  • Liniger M, Summerfield A, Ruggli N (2012) MDA5 can be exploited as efficacious genetic adjuvant for DNA vaccination against lethal H5N1 influenza virus infection in chickens. PLoS One 7: e49952.
  • Liu MA (2011) DNA vaccines: an historical perspective and view to the future. Immunol Rev 239: 62-84.
  • Mor G (1998) Plasmid DNA: a new era in vaccinology. Biochem Pharmacol 55: 1151-1153.
  • Moss RB (2009) Prospects for control of emerging infectious diseases with plasmid DNA vaccines. Journal of immune based therapies and vaccines 7: 3.
  • Ogunremi O, Pasick J, Kobinger GP, Hannaman D, Berhane Y, Clavijo A, van Drunen Littel-van den Hurk S (2013) A single electroporation delivery of a DNA vaccine coding for the hemagglutinin gene of Asian H5N1 avian influenza generated a protective antibody response in chickens against a North American virus strain. Clin Vaccine Immunol 20: 491-500.
  • Osterhaus A, Fouchier R, Rimmelzwaan G (2011) Towards universal influenza vaccines? Philos Trans R Soc Lond B Biol Sci 366: 2766-2773.
  • Oveissi S, Omar AR, Yusoff K, Jahanshiri F, Hassan SS (2010) DNA vaccine encoding avian influenza virus H5 and Esat-6 of Mycobacterium tuberculosis improved antibody responses against AIV in chickens. Comp Immunol Microbiol Infectious Dis 33: 491-503.
  • Patel A, Dong JC, Trost B, Richardson JS, Tohme S, Babiuk S, Kusalik A, Kung SK, Kobinger GP (2012a) Pentamers not found in the universal proteome can enhance antigen specific immune responses and adjuvant vaccines. PLoS One 7: e43802.
  • Patel A, Gray M, Li Y, Kobasa D, Yao X, Kobinger GP (2012b) Co-administration of certain DNA vaccine combinations expressing different H5N1 influenza virus antigens can be beneficial or detrimental to immune protection. Vaccine 30: 626-636.
  • Rao SS, Kong WP, Wei CJ, Van Hoeven N, Gorres JP, Nason M, Andersen H, Tumpey TM, Nabel GJ (2010) Comparative efficacy of hemagglutinin, nucleoprotein, and matrix 2 protein gene-based vaccination against H5N1 influenza in mouse and ferret. PLoS One 5: e9812.
  • Shan S, Jiang Y, Bu Z, Ellis T, Zeng X, Edwards J, Tian G, Li Y, Ge J, Chen H, Fenwick S (2011) Strategies for improving the efficacy of a H6 subtype avian influenza DNA vaccine in chickens. J Virol Methods 173: 220-226.
  • Shen X, Söderholm J, Lin F, Kobinger G, Bello A, Gregg DA, Broderick KE, Sardesai NY (2012) Influenza A vaccines using linear expression cassettes delivered via electroporation afford full protection against challenge in a mouse model. Vaccine 30: 6946-6954.
  • Smith LR, Wloch MK, Ye M, Reyes LR, Boutsaboualoy S, Dunne CE, Chaplin JA, Rusalov D, Rolland AP, Fisher CL, Al-Ibrahim MS, Kabongo ML, Steigbigel R, Belshe RB, Kitt ER, Chu AH, Moss RB (2010) Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin. Vaccine 28: 2565-2572.
  • Spackman E, Swayne DE (2013) Vaccination of gallinaceous poultry for H5N1 highly pathogenic avian influenza: current questions and new technology. Virus Res 178: 121-132.
  • Stachyra A, Góra-Sochacka A, Sawicka R, Florys K, Saczyńska V, Olszewska M, Pikuła A, Śmietanka K, Minta Z, Szewczyk B, Zagórski W, Sirko A (2014) Highly immunogenic prime-boost DNA vaccination protects chickens against challenge with homologous and heterologous H5N1 virus. Trials Vaccinol 3: 40-46.
  • Steel J, Lowen AC, Wang TT, Yondola M, Gao Q, Haye K, Garcia-Sastre A, Palese P (2010) Influenza virus vaccine based on the conserved hemagglutinin stalk domain. mBio 1 pii: e00018-10; doi: 10.1128/mBio.00018-10.
  • Suguitan AL, Cheng X, Wang W, Wang S, Jin H, Lu S (2011) Influenza H5 hemagglutinin DNA primes the antibody response elicited by the live attenuated influenza A/Vietnam/1203/2004 vaccine in ferrets. PLoS One 6: e21942.
  • Ulmer JB (2002) Influenza DNA vaccines. Vaccine 20 (Suppl 2): S74-S76.
  • van den Berg JH, Nuijen B, Schumacher TN, Haanen JB, Storm G, Beijnen JH, Hennink WE (2010) Synthetic vehicles for DNA vaccination. J Drug Target 18: 1-14.
  • van Drunen Littel-van den Hurk S, Babiuk SL, Babiuk LA (2004) Strategies for improved formulation and delivery of DNA vaccines to veterinary target species. Immunol Rev 199: 113-125.
  • Wang S, Hackett A, Jia N, Zhang C, Zhang L, Parker C, Zhou A, Li J, Cao WC, Huang Z, Li Y, Lu S (2011) Polyvalent DNA vaccines expressing HA antigens of H5N1 influenza viruses with an optimized leader sequence elicit cross-protective antibody responses. PLoS One 6: e28757.
  • WHO (2007) Guidelines for assuring the quality and non-clinical safety evaluation of DNA vaccines, TRS 941, Annex 1. available on line:
  • Williams J (2013) Vector Design for Improved DNA Vaccine Efficacy, Safety and Production. Vaccines 1: 225-249.
  • Xu K, Ling ZY, Sun L, Xu Y, Bian C, He Y, Lu W, Chen Z, Sun B (2011) Broad humoral and cellular immunity elicited by a bivalent DNA vaccine encoding HA and NP genes from an H5N1 virus. Viral Immunol 24: 45-56.
  • Xu Y, Yuen PW, Lam JK (2014) Intranasal DNA vaccine for protection against respiratory infectious diseases: the delivery perspectives. Pharmaceutics 6: 378-415.
  • Zhao K, Shi X, Zhao Y, Wei H, Sun Q, Huang T, Zhang X, Wang Y (2011) Preparation and immunological effectiveness of a swine influenza DNA vaccine encapsulated in chitosan nanoparticles. Vaccine 29: 8549-8556.
  • Zhou F, Wang G, Buchy P, Cai Z, Chen H, Chen Z, Cheng G, Wan XF, Deubel V, Zhou P (2012) A triclade DNA vaccine designed on the basis of a comprehensive serologic study elicits neutralizing antibody responses against all clades and subclades of highly pathogenic avian influenza H5N1 viruses. J Virol 86: 6970-6978.
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