黄保英,阮力,王文玲

• 1:中国疾病预防控制中心病毒病预防控制所病毒病应急技术中心

摘要(Abstract)：

<正>流感是由流感病毒引起的急性呼吸道传染病,全世界每年约有5%~15%人口受流感病毒的影响,其中严重病例有300~500万,因流感而死亡人数为25~50万[1-2]。甲型流感病毒亚型多,变异大,

关键词(KeyWords)：

Abstract:

Keywords:

基金项目(Foundation): 国家863计划资助(2006AA02A203)

作者(Author): 黄保英,阮力,王文玲

DOI: 10.13242/j.cnki.bingduxuebao.002161

参考文献(References)：

• [1]Sambhara S,Stephenson I.Moving influenza vaccinesforward[J].Expert Review of Vaccines,2009,8(4):375-377.
• [2]Carrat F,Flahault.A.Influenza vaccine:The challengeof antigenic drift[J].Vaccine,2007,25(39-40):6852-6862.
• [3]Palese P.Influenza:old and new threats[J].Nat Med,2004,10(12 Suppl):S82-87.
• [4]Kilbourne E D.Influenza pandemics of the 20th century[J].Emerg Infect Dis,2006,12(1):9-14.
• [5]Scalera N M,Mossad S B.The first pandemic of the21st century:a review of the 2009 pandemic variant in-fluenza A(H1N1)virus[J].Postgrad Med,2009,121(5):43-47.
• [6]Subbarao K,Murphy B R,Fauci A S.Development ofeffective vaccines against pandemic influenza[J].Immu-nity,2006,24(1):5-9.
• [7]Gerdil C.The annual production cycle for influenza vac-cine[J].Vaccine,2003,21(16):1776-1779.
• [8]Palese P.Making better influenza virus vaccines?[J].Emerg Infect Dis,2006,12(1):61-65.
• [9]Ito T,Gorman O T,Kawaoka Y.Evolutionary analysisof the influenza A virus M gene with comparison of theM1 and M2 protein[J].J Virol,1991,65(10):5491-5498.
• [10]De Filette M,Fiers W,Martens W,et al.Improveddesign and intranasal delivery of an M2e-based humaninfluenza A vaccine[J].Vaccine,2006,24(44-46):6597-6601.
• [11]Xavier Saelens.The influenza matrix protein 2 as a vac-cine target[J].Expert Rev Vaccines,2008,3(2):167-178.
• [12]Schotsaert M,De Filette M,Fiers W,et al.UniversalM2 ectodomain-based influenza A vaccines:preclinicaland clinical developments[J].Expert Rev Vaccines,2009,8(4):499-508.
• [13]Zebedee S L,Richardson C D,Mozdzanowska K,etal.Characterization of the influenza virus M2 integralmembrane protein and expression at the infected-cellsurface from cloned cDNA[J].J Virol,1985,56(2):502-511.
• [14]Zebedee S L,Lamb R A.Influenza A virus M2 pro-tein:monoclonal antibody restriction of virus growthand detection of M2 in virions[J].J Virol,1988,62(8):2762-2772.
• [15]Feng J,Zhang M,Mozdzanowska K,et al.InfluenzaA virus infection engenders a poor antibody response a-gainst the ectodomain of matrix protein 2[J].Virol J,2006,6(3):102.
• [16]Beerli R R,Bauer M,Schmitz N,et al.Prophylacticand therapeutic activity of fully human monoclonal anti-bodies directed against influenza A M2 protein[J].Virol J,2009,21(6):224.
• [17]Wang R,Song A,Levin J,et al.Therapeutic potentialof a fully human monoclonal antibody against influenzaA virus M2 protein[J].Antiviral Res,2008,80(2):168-177.
• [18]Black R A,Rota P A,Gorodkova N,et al.Antibodyresponse to the M2 protein of influenza A virus ex-pressed in insect cells[J].J Gen Virol,1993,74(1):143-146.
• [19]Treanor J J,Tierney E L,Zebedee S L,et al.Passive-ly transferred monoclonal antibody to the M2 proteininhibits influenza A virus replication in mice[J].J Vir-ol,1990,64(3):1375-1377.
• [20]Jegerlehner A,Schmitz N,Storni T,et al.Influenza Avaccine based on the extracellular domain of M2:weakprotection mediated via antibody-dependent NK cell ac-tivity[J].J Immunol,2004,172(9):5598-5605.
• [21]Neirynck S,Deroo T,Saelens X,et al.A universal in-fluenza A vaccine based on the extracellular domain ofthe M2 protein[J].Nat Med,1999,15(10):1157-1163.
• [22]Fiers W,De Filette M,Birkett A,et al.A“universal”human influenza A vaccine[J].Virus Res,2004,103(1-2):173-176.
• [23]De Filette M,Min JW,Birkett A,et al.Universal in-fluenza A vaccine:optimization of M2-based constructs[J].Virology,2005,337(1):149-161.
• [24]De Filette M,Ramne A,Birkett A,et al.The univer-sal influenza vaccine M2e-HBc administered intranasal-ly in combination with the adjuvant CTA1-DD providescomplete protection[J].Vaccine,2006,24(5):544-551.
• [25]De Filette M,Martens W,Smet A,et al.Universalinfluenza A M2e-HBc vaccine protects against diseaseeven in the presence of pre-existing anti-HBc antibodies[J].Vaccine,2008,26(51):6503-6507.
• [26]Fiers W,De Filette M,Bakkouri E K,et al.M2e-based universal influenza A vaccine[J].Vaccine,2009,27(45):6280-6283.
• [27]Ionescu R M,Przysiecki C T,Liang X,et al.Pharma-ceutical and immunological evaluation of human papillo-mavirus viruslike particle as an antigen carrier[J].JPharm Sci,2006,95(1):70-79.
• [28]Bessa J,Schmitz N,Hinton H J,et al.Efficient in-duction of mucosal and systemic immune responses byvirus-like particles administered intranasally:implica-tions for vaccine design[J].Eur J Immunol,2008,38(1):114-126.
• [29]Tissot A C,Renhofa R,Schmitz N,et al.Versatile vi-rus-like particle carrier for epitope based vaccines[J].PLoS One,2010,5(3):e9809.
• [30]Denis J,Acosta R E,Zhao Y,et al.Development of auniversal influenza A vaccine based on the M2e peptidefused to the papaya mosaic virus(PapMV)vaccineplatform[J].Vaccine,2008,26(27-28):3395-3403.
• [31]Slepushkin V A,Katz JM,Black RA,et al.Protectionof mice against influenza A virus challenge by vaccina-tion with baculovirus-expressed M2 protein[J].Vac-cine,1995,13(15):1399-1402.
• [32]Frace A M,Klimov A I,Rowe T,et al.Modified M2proteins produce heterotypic immunity against influenzaA virus[J].Vaccine,1999,17(18):2237-2244.
• [33]Huleatt J W,Nakaar V,Desai P,et al.Potent immu-nogenicity and efficacy of a universal influenza vaccinecandidate comprising a recombinant fusion protein link-ing influenza M2e to the TLR5 ligand flagellin[J].Vaccine,2008,26(2):201-214.
• [34]BUSINESS WIRE.VaxInnate's Universal Flu VaccineCandidate Shown Safe and Immunogenic in Phase Iclinical Study[EB/OL].[2009-4-30]http://www.fiercebiotech.com/press-releases/vaxinnates-universal-flu-vaccine-candidate-shown-safe-and-immunogenic-phase-i-clinica
• [35]Eliasson D G,El Bakkouri K,Sch n K,et al.CTA1-M2e-DD:a novel mucosal adjuvant targeted influenzavaccine[J].Vaccine,2008,26(9):1243-1252.
• [36]De Filette M,Martens W,Roose K,et al.An influen-za A vaccine based on tetrameric ectodomain of matrixprotein 2[J].J Biol Chem,2008,283(17):11382-11387.
• [37]Wu F,Huang J H,Yuan X Y,et al.Characterizationof immunity induced by M2e of influenza virus[J].Vaccine,2007,25(52):8868-8873.
• [38]Wu F,Yuan XY,Li J,et al.The co-administration ofCpG-ODN influenced protective activity of influenzaM2e vaccine[J].Vaccine,2009,27(32):4320-4324.
• [39]Wu F,Yuan X Y,Huang W S,et al.Heterosubtypicprotection conferred by combined vaccination with M2epeptide and split influenza vaccine[J].Vaccine,2009,27(43):6095-6101.
• [40]Mozdzanowska K,Feng J,Eid M,et al.Induction ofinfluenza type A virus-specific resistance by immuniza-tion of mice with a synthetic multiple antigenic peptidevaccine that contains ectodomains of matrix protein 2[J].Vaccine,2003,21(19-20):2616-2626.
• [41]Zhao G,Lin Y,Du L,et al.An M2e-based multipleantigenic peptide vaccine protects mice from lethal chal-lenge with divergent H5N1 influenza viruses[J].VirolJ,2010,7:9.
• [42]Pejoski D,Zeng W,Rockman S,et al.A lipopeptidebased on the M2 and HA proteins of influenza A viru-ses induces protective antibody[J].Immunol Cell Biol,2010,1-7.
• [43]Fan J,Liang X,Horton M S,et al.Preclinical studyof influenza virus A M2 peptide conjugate vaccines inmice,ferrets,and rhesus monkeys[J].Vaccine,2004,22(23-24):2993-3003.
• [44]Fu T M,Grimm K M,Citron M P,et al.Comparativeimmunogenicity evaluations of influenza A virus M2peptide as recombinant virus like particle or conjugatevaccines in mice and monkeys[J].Vaccine,2009,27(9):1440-1447.
• [45]Zou P,Liu W,Chen Y H.The epitope recognized by amonoclonal antibody in influenza A virus M2 protein isimmunogenic and confers immune protection[J].IntImmunopharmacol,2005,5(4):631-635.
• [46]Okuda K,Ihata A,Watabe S,et al.Protective immu-nity against influenza A virus induced by immunizationwith DNA plasmid containing influenza M gene[J].Vaccine,2001,19(27):3681-9361.
• [47]Jimenez G S,Planchon R,Wei Q,et al.Vaxfectin-for-mulated influenza DNA vaccines encoding NP and M2viral proteins protect mice against lethal viral challenge[J].Hum Vaccine,2007,3(5):157-164.
• [48]Lalor P A,Webby R J,Morrow J,et al.PlasmidDNA-based vaccines protect mice and ferrets against le-thal challenge with A/Vietnam/1203/04(H5N1)in-fluenza virus[J].J Infect Dis,2008,197(12):1643-1652.
• [49]Heinen P P,Rijsewijk F A,Boer E A,et al.Vaccina-tion of pigs with a DNA construct expressing an influ-enza virus M2-nucleoprotein fusion protein exacerbatesdisease after challenge with influenza A virus[J].JGen Virol,2002,83(8):1851-1859.
• [50]Tompkins S M,Zhao Z S,Lo C Y,et al.Matrix pro-tein 2 vaccination and protection against influenza viru-ses,including subtype H5N1[J].Emerg Infect Dis,2007,13(3):426-435.
• [51]Lo C Y,Wu Z,Misplon JA,et al.Comparison of vac-cines for induction of heterosubtypic immunity to influ-enza A virus:cold-adapted vaccine versus DNA prime-adenovirus boost strategies[J].Vaccine,2008,26(17):2062-2072.
• [52]Price G E,Soboleski M R,Lo C Y,et al.Vaccinationfocusing immunity on conserved antigens protects miceand ferrets against virulent H1N1 and H5N1 influenzaA viruses[J].Vaccine,2009,27(47):6512-6521.