Abstract
Prophylactic DNA vaccines against the influenza virus are promising alternatives to conventional vaccines. In this study, we generated two candidate gene-based influenza vaccines encoding either the seasonal or pandemic hemagglutinin antigen (HA) from the strains A/New Caledonia/20/99 (H1N1) (pV1A5) and A/California/04/2009 (H1N1) (pVEH1), respectively. After verifying antigen expression, the immunogenicity of the vaccines delivered intramuscularly with electroporation was tested in a mouse model. Sera of immunized animals were tested in hemagglutination inhibition assays and by ELISA for the presence of HA-specific antibodies. HA-specific T-cells were also measured in IFN-γ ELISpot assays. The protective efficacy of the candidate influenza vaccines was evaluated by measuring mortality rates and body weight after a challenge with 100 LD50 of mouse-adapted A/New Caledonia/20/99 (H1N1). Mice immunized with either one of the two vaccines showed significantly higher T cell and humoral immune responses (P<0.05) than the pVAX1 control group. Additionally, the pV1A5 vaccine effectively protected the mice against a lethal homologous mouse-adapted virus challenge with a survival rate of 100% compared with a 40% survival rate in the pVEH1 vaccinated group (P<0.05). Our study indicates that the seasonal influenza DNA vaccine completely protects against the homologous A/New Caledonia/20/99 virus (H1N1), while the pandemic influenza DNA vaccine only partially protects against this virus.
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Fries L F, Dillon S B, Hildreth J E, et al. Safety and immunogenicity of a recombinant protein influenza A vaccine in adult human volunteers and protective efficacy against wild-type H1N1 virus challenge. J Infect Dis, 1993, 167: 593–601 8440931, 10.1093/infdis/167.3.593, 1:STN:280:DyaK3s7nvFOrsA%3D%3D
Steitz J, Barlow P G, Hossain J, et al. A candidate H1N1 pandemic influenza vaccine elicits protective immunity in mice. PLoS One, 2010, 5: e10492 20463955, 10.1371/journal.pone.0010492
Kong W P, Hood C, Yang Z Y, et al. Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination. Proc Natl Acad Sci USA, 2006, 103: 15987–15991 17043214, 10.1073/pnas.0607564103, 1:CAS:528:DC%2BD28XhtFyktLvE
Kodihalli S, Kobasa D L, Webster R G. Strategies for inducing protection against avian influenza A virus subtypes with DNA vaccines. Vaccine, 2000, 18: 2592–2599 10775793, 10.1016/S0264-410X(99)00485-5, 1:CAS:528:DC%2BD3cXkt1Crs7g%3D
Kodihalli S, Goto H, Kobasa D L, et al. DNA vaccine encoding hemagglutinin provides protective immunity against H5N1 influenza virus infection in mice. J Virol, 1999, 73: 2094–2098 9971791, 1:CAS:528:DyaK1MXhvVWnsb0%3D
Ljungberg K, Wahren B, Almqvist J, et al. Effective construction of DNA vaccines against variable influenza genes by homologous recombination. Virology, 2000, 268: 244–250 10704333, 10.1006/viro.2000.0199, 1:CAS:528:DC%2BD3cXhsFWjsrc%3D
Ljungberg K, Kolmskog C, Wahren B, et al. DNA vaccination of ferrets with chimeric influenza A virus hemagglutinin (H3) genes. Vaccine, 2002, 20: 2045–2052 11972972, 10.1016/S0264-410X(02)00049-X, 1:CAS:528:DC%2BD38XjtVejsbo%3D
Lee C W, Senne D A, Suarez D L. Development of hemagglutinin subtype-specific reference antisera by DNA vaccination of chickens. Avian Dis, 2003, 47: 1051–1056 14575109, 10.1637/0005-2086-47.s3.1051, 1:STN:280:DC%2BD3svpslOrsA%3D%3D
Chen Z, Sahashi Y, Matsuo K, et al. Comparison of the ability of viral protein-expressing plasmid DNAs to protect against influenza. Vaccine, 1998, 16: 1544–1549 9711802, 10.1016/S0264-410X(98)00043-7, 1:CAS:528:DyaK1cXlsFahtrc%3D
Chen Z, Kadowaki S, Hagiwara Y, et al. Cross-protection against a lethal influenza virus infection by DNA vaccine to neuraminidase. Vaccine, 2000, 18: 3214–3222 10869766, 10.1016/S0264-410X(00)00149-3, 1:CAS:528:DC%2BD3cXktlOhs7w%3D
Kadowaki S, Chen Z, Asanuma H, et al. Protection against influenza virus infection in mice immunized by administration of hemagglutinin-expressing DNAs with electroporation. Vaccine, 2000, 18: 2779–2788 10812219, 10.1016/S0264-410X(00)00087-6, 1:STN:280:DC%2BD3cvhs1Snsg%3D%3D
Chen Z, Kadowaki S, Hagiwara Y, et al. Protection against influenza B virus infection by immunization with DNA vaccines. Vaccine, 2001, 19: 1446–1455 11163667, 10.1016/S0264-410X(00)00351-0, 1:CAS:528:DC%2BD3MXktl2jsg%3D%3D
Chen J, Fang F, Li X, et al. Protection against influenza virus infection in BALB/c mice immunized with a single dose of neuraminidase-expressing DNAs by electroporation. Vaccine, 2005, 23: 4322–4328 15925433, 10.1016/j.vaccine.2005.03.035, 1:CAS:528:DC%2BD2MXlvFOjtr0%3D
Luxembourg A, Evans C F, Hannaman D. Electroporation-based DNA immunisation: Translation to the clinic. Expert Opin Biol Ther, 2007, 7: 1647–1664 17961089, 10.1517/14712598.7.11.1647, 1:CAS:528:DC%2BD2sXht1ams73O
Luckay A, Sidhu M K, Kjeken R, et al. Effect of plasmid DNA vaccine design and in vivo electroporation on the resulting vaccine-specific immune responses in rhesus macaques. J Virol, 2007 81: 5257–5269 17329330, 10.1128/JVI.00055-07, 1:CAS:528:DC%2BD2sXls1GrsbY%3D
Nguyen H H, Zemlin M, Ivanov I I, et al. Heterosubtypic immunity to influenza A virus infection requires a properly diversified antibody repertoire. J Virol, 2007, 81: 9331–9338 17567700, 10.1128/JVI.00751-07, 1:CAS:528:DC%2BD2sXps1amtrY%3D
Zhang L, Nolan E, Kreitschitz S, et al. Enhanced delivery of naked DNA to the skin by non-invasive in vivo electroporation. Biochim Biophys Acta, 2002, 1572: 1–9 12204326, 1:CAS:528:DC%2BD38XmsVCktLw%3D
Rowe T, Abernathy R A, Hu-Primmer J, et al. Detection of antibody to avian influenza A (H5N1) virus in human serum by using a combination of serologic assays. J Clin Microbiol, 1999, 37: 937–943 10074505, 1:CAS:528:DyaK1MXitFGksbc%3D
Holman D H, Wang D, Raja N U, et al. Multi-antigen vaccines based on complex adenovirus vectors induce protective immune responses against H5N1 avian influenza viruses. Vaccine, 2008, 26: 2627–2639 18395306, 10.1016/j.vaccine.2008.02.053, 1:CAS:528:DC%2BD1cXlslygu7g%3D
Leili J. Isolation of avian influenza virus and study on construction and immunogenicity of multi-epitopes recombinants. Dissertation for PhD degree. Changchun: Jilin University, 2006
Cherbonnel M, Rousset J, Jestin V. Strategies to improve protection against low-pathogenicity H7 avian influenza virus infection using DNA vaccines. Avian Dis, 2003, 47: 1181–1186 14575138, 10.1637/0005-2086-47.s3.1181, 1:STN:280:DC%2BD3svpslyisw%3D%3D
Qiu M, Fang F, Chen Y, et al. Protection against avian influenza H9N2 virus challenge by immunization with hemagglutinin- or neuraminidase-expressing DNA in BALB/c mice. Biochem Biophys Res Commun, 2006, 343: 1124–1131 16580631, 10.1016/j.bbrc.2006.03.088, 1:CAS:528:DC%2BD28XksFaiu7k%3D
Laddy D J, Yan J, Corbitt N, et al. Immunogenicity of novel consensus-based DNA vaccines against avian influenza. Vaccine, 2007, 25: 2984–2989 17306909, 10.1016/j.vaccine.2007.01.063, 1:CAS:528:DC%2BD2sXjslSrsro%3D
Wenlong N. Screening of influenza functional epitopes and study on design and immunogenicity of combined multi-epitope DNA vaccine. Dissertation for PhD degree. Changchun: Jilin University, 2009
Carroll S M, Paulson J C. Differential infection of receptor-modified host cells by receptor-specific influenza viruses. Virus Res, 1985, 3: 165–179 4060886, 10.1016/0168-1702(85)90006-1, 1:CAS:528:DyaL2MXmtFamtLk%3D
Wang S X, Taaffe J, Parker C, et al. Hemagglutinin (HA) proteins from H1 and H3 serotypes of influenza A viruses require different antigen designs for the induction of optimal protective antibody responses as studied by codon-optimized HA DNA vaccines. J Virol, 2006, 80: 11628–11637 16987975, 10.1128/JVI.01065-06, 1:CAS:528:DC%2BD28Xht12hu7jE
Zheng L Y, Wang F Y, Yang Z D, et al. A single immunization with HA DNA vaccine by electroporation induces early protection against H5N1 avian influenza virus challenge in mice. BMC Infect Dis, 2009, 9: 17 19216752, 10.1186/1471-2334-9-17
Zhang L, Widera G, Rabussay D. Enhancement of the effectiveness of electroporation-augmented cutaneous DNA vaccination by a particulate adjuvant. Bioelectrochem, 2004, 63: 369–373 10.1016/j.bioelechem.2003.11.011, 1:CAS:528:DC%2BD2cXjsVWitLo%3D
De Groot A S, Arditoa M, McClaine E M, et al. Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008–2009 conventional influenza vaccine. Vaccine, 2009, 27: 5740–5747 19660593, 10.1016/j.vaccine.2009.07.040
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Tan, L., Lu, H., Zhang, D. et al. Efficacy of seasonal pandemic influenza hemagglutinin DNA vaccines delivered by electroporation against aseasonal H1N1 virus challenge in mice. Sci. China Life Sci. 54, 293–299 (2011). https://doi.org/10.1007/s11427-011-4150-5
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DOI: https://doi.org/10.1007/s11427-011-4150-5