活载体疫苗的研究进展
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摘要
免疫学与生物工程等领域取得的巨大进步,为发展基因工程疫苗提供了更多的理论和技术支持。活载体疫苗(Live Vector Vaccine,LVV),是以细菌或病毒作为外源抗原和治疗因子的载体系统,是目前最具发展潜力的基因工程疫苗之一。不同疫苗载体、抗原呈递方式和对宿主细胞免疫系统启动机制等研究的深入,开拓了活载体疫苗的实用价值。对国际上相关研究予以重点综述,以期为深入开展该领域研究提供依据。
The enormous progresses in immunology and bioengineering and other fields provided more theoretical and technological supports on the development of genetic engineering vaccines. Live vector vaccine( LVV) used as carrier system for foreign antigen and therapeutic factors,is one of the most potential-endowed development in genetic engineering vaccines. The intensive studies on different vaccine vectors,the present style of antigen,and the start-up mechanism of the immune system of the host cells have pioneered the practical application value of the LVV. The international research progression in the LVV correlated studies were summarized in this paper,so as to provide foundation to deeply carry out the study in the field of the LVV.
The enormous progresses in immunology and bioengineering and other fields provided more theoretical and technological supports on the development of genetic engineering vaccines. Live vector vaccine( LVV) used as carrier system for foreign antigen and therapeutic factors,is one of the most potential-endowed development in genetic engineering vaccines. The intensive studies on different vaccine vectors,the present style of antigen,and the start-up mechanism of the immune system of the host cells have pioneered the practical application value of the LVV. The international research progression in the LVV correlated studies were summarized in this paper,so as to provide foundation to deeply carry out the study in the field of the LVV.
引文
[1]Toussaint B,Chauchet X,Wang Y,et al.Live-attenuated bacteria as a cancer vaccine vector[J].Expert Review of Vaccines,2013,12(10):1139-1154.
[2]Bloom BR.Vaccines for the Third World[J].Nature,1989,342(6246):115-120.
[3]Hudson P,Gorton TS,Papazisi L,et al.Identification of a virulence-associated determinant,dihydrolipoamide dehydrogenase(lpd),in Mycoplasma gallisepticum through in vivo screening of transposon mutants[J].Infection&Immunity,2006,74(2):931-939.
[4]Ogra PL,Faden H,Welliver RC.Vaccination Strategies for Mucosal Immune Responses[J].Clinical Microbiology Reviews,2001,14(2):430-445.
[5]Wick MJ.The role of dendritic cells in the immune response to Salmonella[J].Immunology Letters,2003,85(2):99-102.
[6]Cong W,Jin H,Jiang C,et al.Attenuated Salmonella choleraesuis-mediated RNAi targeted to conserved regions against foot-and-mouth disease virus in guinea pigs and swine[J].Veterinary Research,2010,41(3):30.
[7]Wang QL,Pan Q,Ma Y,et al.An attenuated Salmonellavectored vaccine elicits protective immunity against Mycobacterium tuberculosis[J].Vaccine,2009,27(48):6712-6722.
[8]Qu D,Wang S,Cai W,et al.Protective effect of a DNA vaccine delivered in attenuated Salmonella typhimurium against Toxoplasma gondii infection in mice[J].Vaccine,2008,26(35):4541-4548.
[9]Manuel ER,Blache CA,Paquette R,et al.Enhancement of cancer vaccine therapy by systemic delivery of a tumor-targeting Salmonella-based STAT3 shRNA suppresses the growth of established melanoma tumors[J].Cancer Research,2011,71(12):4183-4191.
[10]Poussin MA,Leitges M,Goldfine H.The ability of Listeria monocytogenes PI-PLC to facilitate escape from the macrophage phagosome is dependent on host PKCbeta[J].Microbial Pathogenesis,2009,46(1):1-5.
[11]Brockstedt DG,Giedlin MA,Leong ML,et al.Listeria-based cancer vaccines that segregate immunogenicity from toxicity[J].Proceedings of the National Academy of Sciences of the United States of America,2004,101(38):13832-13837.
[12]Saklani-Jusforgues H,Fontan E,Soussi N,et al.Enteral immunization with attenuated recombinant Listeria monocytogenes as a live vaccine vector:organ-dependent dynamics of CD4 T lymphocytes reactive to a Leishmania major tracer epitope[J].Infection&Immunity,2003,71(3):1083-1090.
[13]Toussaint B,Chauchet X,Wang Y,et al.Live-attenuated bacteria as a cancer vaccine vector[J].Expert Review of Vaccines,2013,12(10):1139-1154.
[14]Miller EA,Spadaccia MR,Norton T,et al.Attenuated Listeria monocytogenes vectors overcome suppressive plasma factors during HIV infection to stimulate myeloid dendritic cells to promote adaptive immunity and reactivation of latent virus[J].Aids Research&Human Retroviruses,2015,31(1):127-136.
[15]Quispe-Tintaya W,Chandra D,Jahangir A,et al.From the Cover:Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(21):8668.
[16]Maciag PC,Radulovic S,Rothman J.The first clinical use of a live-attenuated Listeria monocytogenes vaccine:a Phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix[J].Vaccine,2009,27(30):3975-3983.
[17]Ruan X,Zhang W.Oral immunization of a live attenuated Escherichia coli,strain expressing a holotoxin-structured adhesin-toxoid fusion(1Fae G-Fed F-LTA2:5LTB)protected young pigs against enterotoxigenic E.coli,(ETEC)infection[J].Vaccine,2013,31(11):1458-1463.
[18]Hiroi T,Goto H,Someya K,et al.HIV mucosal vaccine:nasal immunization with r BCG-V3J1 induces a long term V3J1peptide-specific neutralizing immunity in Th1-and Th2-deficient conditions[J].International Congress,2001,167(10):5862-5867.
[19]Brzu S,Arondel J,Guillot S,et al.Immunogenicity of Ipa CHybrid Proteins Expressed in the Shigella flexneri 2a Vaccine Candidate SC602[J].Infection&Immunity,1998,66(1):77-82.
[20]Periaswamy B.Salmonella Typhimurium live attenuated vaccine with improved safety in immunocompromised mice[J].Plos One,2012,7(9):e45433.
[21]Wang Z.Response of complement expression to challenge with lipopolysaccharide in embryos/larvae of zebrafish Danio rerio:acquisition of immunocompetent complement[J].Fish&Shellfish Immunology,2008,25(3):264-270.
[22]Mohamadzadeh M,Duong T,Hoover T,et al.Targeting mucosal dendritic cells with microbial antigens from probiotic lactic acid bacteria[J].Expert Review of Vaccines,2008,7(7):163-174.
[23]Wells JM,Mercenier A.Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria[J].Nature Reviews Microbiology,2008,6(5):349-362.
[24]Wang Z,Gao J,Yu Q,et al.Oral immunization with recombinant Lactococcus lactis expressing the hemagglutinin of the avian influenza virus induces mucosal and systemic immune responses[J].Future Microbiology,2012,7(8):1003-1010.
[25]Wei CH,Liu JK,Hou XL,et al.Immunogenicity and protective efficacy of orally or intranasally administered recombinant Lactobacillus casei expressing ETEC K99[J].Vaccine,2010,28(24):4113-4118.
[26]Felix Hugentobler,Karen K.Yam,Joshua Gillard,et al.Immunization against,Leishmania major,Infection Using LACK-and IL-12-Expressing,Lactococcus lactis,Induces Delay in Footpad Swelling[J].Plos One,2012,7(2):e30945.
[27]Bermúdezhumarán LG,Kharrat P,Chatel JM,et al.Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines[J].Microbial Cell Factories,2011,10(1):S4.
[28]Draper SJ,Cottingham MG,Gilbert SC.Utilizing poxviral vectored vaccines for antibody induction—Progress and prospects[J].Vaccine,2013,31(39):4223-4230.
[29]Fernandez-Sainz I,Medina GN,Ramirez-Medina E,et al.Adenovirus-vectored foot-and-mouth disease vaccine confers early and full protection against FMDV O1 Manisa in swine[J].Virology,2017,502:123-132.
[30]Yao L,Wu CX,Zheng K,et al.Immunogenic response to a recombinant pseudorabies virus carrying bp26 gene of Brucella melitensis in mice[J].Research in Veterinary Science,2015,100:61-67.
[31]Kim SH,Paldurai A,Samal SK.A novel chimeric Newcastle disease virus vectored vaccine against highly pathogenic avian influenza virus[J].Virology,2017,503:31.
[32]Han SS,Lee J,Jung Y,et al.Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system[J].Vaccine,2015,33(38):4827.
[33]Tabynov K,Yespembetov B,Matikhan N,et al.First evaluation of an influenza viral vector based Brucella abortus vaccine in sheep and goats:Assessment of safety,immunogenicity and protective efficacy against Brucella melitensis infection[J].Veterinary Microbiology,2016,197:15-20.
[34]Zanotto C,Pozzi E,Pacchioni S,et al.Canarypox and fowlpox viruses as recombinant vaccine vectors:a biological and immunological comparison[J].Antiviral Research,2010,88(1):53-63.
[35]Han N,Li Y,Sun C,et al.Construction and Immunogenicity of a Recombinant Pseudorabies Virus Expressing the Rabies Virus Glycoprotein and EGFP[J].Journal of Animal&Veterinary Advances,2012,11(4):566-571.
[36]Crotty S,Andino R.Poliovirus vaccine strains as mucosal vaccine vectors and their potential use to develop an AIDS vaccine[J].Advanced Drug Delivery Reviews,2004,56(6):835-852.
[37]Basavarajappa MK,Kumar S,Khattar SK,et al.A recombinant Newcastle disease virus(NDV)expressing infectious laryngotracheitis virus(ILTV)surface glycoprotein D protects against highly virulent ILTV and NDV challenges in chickens[J].Vaccine,2014,32(28):3555-3563.
[38]Frey J.Biological safety concepts of genetically modified live bacterial vaccines[J].Vaccine,2007,25(30):5598.
[39]Kim K,Jeong JH,Lim D,et al.A Novel Balanced-Lethal Host-Vector System Based on glm S[J].Plos One,2013,8(3):e60511.
[40]Yan Y,Mu W,Zhang L,et al.Asd-based balanced-lethal system in attenuated Edwardsiella tarda,to express aheterologous antigen for a multivalent bacterial vaccine[J].Fish&Shellfish Immunology,2013,34(5):1188.
[41]Wei Xin,Soo-Young Wanda,Xiangmin Zhang,et al.The Asd+-Dad B+dual-plasmid system offers a novel means to deliver multiple protective antigens by a recombinant attenuated Salmonella vaccine[J].Infection&Immunity,2012,80(10):3621-3633.
[42]Vidal L,López-Santín J,Caminal G,et al.Development of an antibiotic-free plasmid selection system based on glycine auxotrophy for recombinant protein overproduction in Escherichia coli[J].J Biotechnol,2008,134(1-2):127-136.
[43]Sciaranghella G,Lakhashe S,Ayashrashkovsky M,et al.A Live Attenuated Listeria monocytogenes Vaccine Vector Expressing SIV Gag Is Safe and Immunogenic in Macaques and Can Be Administered Repeatedly[J].Vaccine,2011,29(3):476-486.
[44]Borsuk S,Mendum TA,Fagundes MQ,et al.Auxotrophic complementation as a selectable marker for stable expression of foreign antigens in Mycobacterium bovis BCG[J].Tuberculosis,2007,87(6):474-480.
[45]Michon C,Langella P,Eijsink VGH,et al.Display of recombinant proteins at the surface of lactic acid bacteria:strategies and applications[J].Microbial Cell Factories,2016,15(1):70.
[46]Fredriksen L,Kleiveland CR,Hult LT,et al.Surface display of N-terminally anchored invasin by Lactobacillus plantarum activates NF-B in monocytes[J].Applied&Environmental Microbiology,2012,78(16):5864-5871.
[47]Audouy SA,Roosmalen MLV,Neef J,et al.Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization[C]//International Conference on Computer Modelling and Simulation.IEEE,2006:39-44.
[48]Zhang J,Masi LD,John B,et al.Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella[J].Microbial Cell Factories,2014,13(1):80.
[49]Wang X,Chen W,Tian Y,et al.Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate[J].Vaccine,2014,32(12):1338-1345.
[50]Fu X,Lin Q,Liu L,et al.Display of ISKNV orf086 protein on the surface of Aeromonas hydrophila and its immunogenicity in Chinese perch(Siniperca chuatsi)[J].Fish&Shellfish Immunology,2016,56:286-293.
[51]MkelA R,Oker-Blom C.Baculovirus Display:A Multifunctional Technology for Gene Delivery and Eukaryotic Library Development[J].Advances in Virus Research,2006,68(68):91-112.
[52]Xu XG,Wang ZS,Zhang Q,et al.Baculovirus surface display of E envelope glycoprotein of Japanese encephalitis virus and its immunogenicity of the displayed proteins in mouse and swine models[J].Vaccine,2011,29(4):636-643.
[53]Zhang J,Chen XW,Tong TZ,et al.Bac Mam virus-based surface display of the infectious bronchitis virus(IBV)S1glycoprotein confers strong protection against virulent IBV challenge in chickens[J].Vaccine,2014,32(6):664-670.
[54]Zhang LX,Zhou JF,Yu ZJ,et al.[Evaluation of influenza A virus nucleoprotein based on baculovirus surface-display technology][J].Bing Du Xue Bao,2013,29(3):265-272.
[55]Xu XG,Liu HJ.Baculovirus surface display of E2 envelope glycoprotein of classical swine fever virus and immunogenicity of the displayed proteins in a mouse model[J].Vaccine,2008,26(43):5455-5460.
[56]Xu XG,Wang ZS,Zhang Q,et al.Baculovirus as a PRRSV and PCV2 bivalent vaccine vector:baculovirus virions displaying simultaneously GP5 glycoprotein of PRRSV and capsid protein of PCV2[J].Journal of virological methods,2012,179(2):359-366.
[57]Zurakowski R,Wodarz D.Model-driven Approaches for in Vitro Combination Therapy using ONYX-015 Replicating Oncolytic Adenovirus[J].Journal of Theoretical Biology,2007,245(1):1-8.
[58]Wang S,Kong Q,Roy Curtiss I.New Technologies in Developing Recombinant Attenuated Salmonella Vaccine Vectors[J].Microbial Pathogenesis,2013,58(5):17-28.
[2]Bloom BR.Vaccines for the Third World[J].Nature,1989,342(6246):115-120.
[3]Hudson P,Gorton TS,Papazisi L,et al.Identification of a virulence-associated determinant,dihydrolipoamide dehydrogenase(lpd),in Mycoplasma gallisepticum through in vivo screening of transposon mutants[J].Infection&Immunity,2006,74(2):931-939.
[4]Ogra PL,Faden H,Welliver RC.Vaccination Strategies for Mucosal Immune Responses[J].Clinical Microbiology Reviews,2001,14(2):430-445.
[5]Wick MJ.The role of dendritic cells in the immune response to Salmonella[J].Immunology Letters,2003,85(2):99-102.
[6]Cong W,Jin H,Jiang C,et al.Attenuated Salmonella choleraesuis-mediated RNAi targeted to conserved regions against foot-and-mouth disease virus in guinea pigs and swine[J].Veterinary Research,2010,41(3):30.
[7]Wang QL,Pan Q,Ma Y,et al.An attenuated Salmonellavectored vaccine elicits protective immunity against Mycobacterium tuberculosis[J].Vaccine,2009,27(48):6712-6722.
[8]Qu D,Wang S,Cai W,et al.Protective effect of a DNA vaccine delivered in attenuated Salmonella typhimurium against Toxoplasma gondii infection in mice[J].Vaccine,2008,26(35):4541-4548.
[9]Manuel ER,Blache CA,Paquette R,et al.Enhancement of cancer vaccine therapy by systemic delivery of a tumor-targeting Salmonella-based STAT3 shRNA suppresses the growth of established melanoma tumors[J].Cancer Research,2011,71(12):4183-4191.
[10]Poussin MA,Leitges M,Goldfine H.The ability of Listeria monocytogenes PI-PLC to facilitate escape from the macrophage phagosome is dependent on host PKCbeta[J].Microbial Pathogenesis,2009,46(1):1-5.
[11]Brockstedt DG,Giedlin MA,Leong ML,et al.Listeria-based cancer vaccines that segregate immunogenicity from toxicity[J].Proceedings of the National Academy of Sciences of the United States of America,2004,101(38):13832-13837.
[12]Saklani-Jusforgues H,Fontan E,Soussi N,et al.Enteral immunization with attenuated recombinant Listeria monocytogenes as a live vaccine vector:organ-dependent dynamics of CD4 T lymphocytes reactive to a Leishmania major tracer epitope[J].Infection&Immunity,2003,71(3):1083-1090.
[13]Toussaint B,Chauchet X,Wang Y,et al.Live-attenuated bacteria as a cancer vaccine vector[J].Expert Review of Vaccines,2013,12(10):1139-1154.
[14]Miller EA,Spadaccia MR,Norton T,et al.Attenuated Listeria monocytogenes vectors overcome suppressive plasma factors during HIV infection to stimulate myeloid dendritic cells to promote adaptive immunity and reactivation of latent virus[J].Aids Research&Human Retroviruses,2015,31(1):127-136.
[15]Quispe-Tintaya W,Chandra D,Jahangir A,et al.From the Cover:Nontoxic radioactive Listeriaat is a highly effective therapy against metastatic pancreatic cancer[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(21):8668.
[16]Maciag PC,Radulovic S,Rothman J.The first clinical use of a live-attenuated Listeria monocytogenes vaccine:a Phase I safety study of Lm-LLO-E7 in patients with advanced carcinoma of the cervix[J].Vaccine,2009,27(30):3975-3983.
[17]Ruan X,Zhang W.Oral immunization of a live attenuated Escherichia coli,strain expressing a holotoxin-structured adhesin-toxoid fusion(1Fae G-Fed F-LTA2:5LTB)protected young pigs against enterotoxigenic E.coli,(ETEC)infection[J].Vaccine,2013,31(11):1458-1463.
[18]Hiroi T,Goto H,Someya K,et al.HIV mucosal vaccine:nasal immunization with r BCG-V3J1 induces a long term V3J1peptide-specific neutralizing immunity in Th1-and Th2-deficient conditions[J].International Congress,2001,167(10):5862-5867.
[19]Brzu S,Arondel J,Guillot S,et al.Immunogenicity of Ipa CHybrid Proteins Expressed in the Shigella flexneri 2a Vaccine Candidate SC602[J].Infection&Immunity,1998,66(1):77-82.
[20]Periaswamy B.Salmonella Typhimurium live attenuated vaccine with improved safety in immunocompromised mice[J].Plos One,2012,7(9):e45433.
[21]Wang Z.Response of complement expression to challenge with lipopolysaccharide in embryos/larvae of zebrafish Danio rerio:acquisition of immunocompetent complement[J].Fish&Shellfish Immunology,2008,25(3):264-270.
[22]Mohamadzadeh M,Duong T,Hoover T,et al.Targeting mucosal dendritic cells with microbial antigens from probiotic lactic acid bacteria[J].Expert Review of Vaccines,2008,7(7):163-174.
[23]Wells JM,Mercenier A.Mucosal delivery of therapeutic and prophylactic molecules using lactic acid bacteria[J].Nature Reviews Microbiology,2008,6(5):349-362.
[24]Wang Z,Gao J,Yu Q,et al.Oral immunization with recombinant Lactococcus lactis expressing the hemagglutinin of the avian influenza virus induces mucosal and systemic immune responses[J].Future Microbiology,2012,7(8):1003-1010.
[25]Wei CH,Liu JK,Hou XL,et al.Immunogenicity and protective efficacy of orally or intranasally administered recombinant Lactobacillus casei expressing ETEC K99[J].Vaccine,2010,28(24):4113-4118.
[26]Felix Hugentobler,Karen K.Yam,Joshua Gillard,et al.Immunization against,Leishmania major,Infection Using LACK-and IL-12-Expressing,Lactococcus lactis,Induces Delay in Footpad Swelling[J].Plos One,2012,7(2):e30945.
[27]Bermúdezhumarán LG,Kharrat P,Chatel JM,et al.Lactococci and lactobacilli as mucosal delivery vectors for therapeutic proteins and DNA vaccines[J].Microbial Cell Factories,2011,10(1):S4.
[28]Draper SJ,Cottingham MG,Gilbert SC.Utilizing poxviral vectored vaccines for antibody induction—Progress and prospects[J].Vaccine,2013,31(39):4223-4230.
[29]Fernandez-Sainz I,Medina GN,Ramirez-Medina E,et al.Adenovirus-vectored foot-and-mouth disease vaccine confers early and full protection against FMDV O1 Manisa in swine[J].Virology,2017,502:123-132.
[30]Yao L,Wu CX,Zheng K,et al.Immunogenic response to a recombinant pseudorabies virus carrying bp26 gene of Brucella melitensis in mice[J].Research in Veterinary Science,2015,100:61-67.
[31]Kim SH,Paldurai A,Samal SK.A novel chimeric Newcastle disease virus vectored vaccine against highly pathogenic avian influenza virus[J].Virology,2017,503:31.
[32]Han SS,Lee J,Jung Y,et al.Development of oral CTL vaccine using a CTP-integrated Sabin 1 poliovirus-based vector system[J].Vaccine,2015,33(38):4827.
[33]Tabynov K,Yespembetov B,Matikhan N,et al.First evaluation of an influenza viral vector based Brucella abortus vaccine in sheep and goats:Assessment of safety,immunogenicity and protective efficacy against Brucella melitensis infection[J].Veterinary Microbiology,2016,197:15-20.
[34]Zanotto C,Pozzi E,Pacchioni S,et al.Canarypox and fowlpox viruses as recombinant vaccine vectors:a biological and immunological comparison[J].Antiviral Research,2010,88(1):53-63.
[35]Han N,Li Y,Sun C,et al.Construction and Immunogenicity of a Recombinant Pseudorabies Virus Expressing the Rabies Virus Glycoprotein and EGFP[J].Journal of Animal&Veterinary Advances,2012,11(4):566-571.
[36]Crotty S,Andino R.Poliovirus vaccine strains as mucosal vaccine vectors and their potential use to develop an AIDS vaccine[J].Advanced Drug Delivery Reviews,2004,56(6):835-852.
[37]Basavarajappa MK,Kumar S,Khattar SK,et al.A recombinant Newcastle disease virus(NDV)expressing infectious laryngotracheitis virus(ILTV)surface glycoprotein D protects against highly virulent ILTV and NDV challenges in chickens[J].Vaccine,2014,32(28):3555-3563.
[38]Frey J.Biological safety concepts of genetically modified live bacterial vaccines[J].Vaccine,2007,25(30):5598.
[39]Kim K,Jeong JH,Lim D,et al.A Novel Balanced-Lethal Host-Vector System Based on glm S[J].Plos One,2013,8(3):e60511.
[40]Yan Y,Mu W,Zhang L,et al.Asd-based balanced-lethal system in attenuated Edwardsiella tarda,to express aheterologous antigen for a multivalent bacterial vaccine[J].Fish&Shellfish Immunology,2013,34(5):1188.
[41]Wei Xin,Soo-Young Wanda,Xiangmin Zhang,et al.The Asd+-Dad B+dual-plasmid system offers a novel means to deliver multiple protective antigens by a recombinant attenuated Salmonella vaccine[J].Infection&Immunity,2012,80(10):3621-3633.
[42]Vidal L,López-Santín J,Caminal G,et al.Development of an antibiotic-free plasmid selection system based on glycine auxotrophy for recombinant protein overproduction in Escherichia coli[J].J Biotechnol,2008,134(1-2):127-136.
[43]Sciaranghella G,Lakhashe S,Ayashrashkovsky M,et al.A Live Attenuated Listeria monocytogenes Vaccine Vector Expressing SIV Gag Is Safe and Immunogenic in Macaques and Can Be Administered Repeatedly[J].Vaccine,2011,29(3):476-486.
[44]Borsuk S,Mendum TA,Fagundes MQ,et al.Auxotrophic complementation as a selectable marker for stable expression of foreign antigens in Mycobacterium bovis BCG[J].Tuberculosis,2007,87(6):474-480.
[45]Michon C,Langella P,Eijsink VGH,et al.Display of recombinant proteins at the surface of lactic acid bacteria:strategies and applications[J].Microbial Cell Factories,2016,15(1):70.
[46]Fredriksen L,Kleiveland CR,Hult LT,et al.Surface display of N-terminally anchored invasin by Lactobacillus plantarum activates NF-B in monocytes[J].Applied&Environmental Microbiology,2012,78(16):5864-5871.
[47]Audouy SA,Roosmalen MLV,Neef J,et al.Lactococcus lactis GEM particles displaying pneumococcal antigens induce local and systemic immune responses following intranasal immunization[C]//International Conference on Computer Modelling and Simulation.IEEE,2006:39-44.
[48]Zhang J,Masi LD,John B,et al.Improved delivery of the OVA-CD4 peptide to T helper cells by polymeric surface display on Salmonella[J].Microbial Cell Factories,2014,13(1):80.
[49]Wang X,Chen W,Tian Y,et al.Surface display of Clonorchis sinensis enolase on Bacillus subtilis spores potentializes an oral vaccine candidate[J].Vaccine,2014,32(12):1338-1345.
[50]Fu X,Lin Q,Liu L,et al.Display of ISKNV orf086 protein on the surface of Aeromonas hydrophila and its immunogenicity in Chinese perch(Siniperca chuatsi)[J].Fish&Shellfish Immunology,2016,56:286-293.
[51]MkelA R,Oker-Blom C.Baculovirus Display:A Multifunctional Technology for Gene Delivery and Eukaryotic Library Development[J].Advances in Virus Research,2006,68(68):91-112.
[52]Xu XG,Wang ZS,Zhang Q,et al.Baculovirus surface display of E envelope glycoprotein of Japanese encephalitis virus and its immunogenicity of the displayed proteins in mouse and swine models[J].Vaccine,2011,29(4):636-643.
[53]Zhang J,Chen XW,Tong TZ,et al.Bac Mam virus-based surface display of the infectious bronchitis virus(IBV)S1glycoprotein confers strong protection against virulent IBV challenge in chickens[J].Vaccine,2014,32(6):664-670.
[54]Zhang LX,Zhou JF,Yu ZJ,et al.[Evaluation of influenza A virus nucleoprotein based on baculovirus surface-display technology][J].Bing Du Xue Bao,2013,29(3):265-272.
[55]Xu XG,Liu HJ.Baculovirus surface display of E2 envelope glycoprotein of classical swine fever virus and immunogenicity of the displayed proteins in a mouse model[J].Vaccine,2008,26(43):5455-5460.
[56]Xu XG,Wang ZS,Zhang Q,et al.Baculovirus as a PRRSV and PCV2 bivalent vaccine vector:baculovirus virions displaying simultaneously GP5 glycoprotein of PRRSV and capsid protein of PCV2[J].Journal of virological methods,2012,179(2):359-366.
[57]Zurakowski R,Wodarz D.Model-driven Approaches for in Vitro Combination Therapy using ONYX-015 Replicating Oncolytic Adenovirus[J].Journal of Theoretical Biology,2007,245(1):1-8.
[58]Wang S,Kong Q,Roy Curtiss I.New Technologies in Developing Recombinant Attenuated Salmonella Vaccine Vectors[J].Microbial Pathogenesis,2013,58(5):17-28.