猪支原体肺炎基因工程疫苗的研究进展
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摘要
猪支原体肺炎(Mycoplasmal pneumoniae of swine,MPS)是由猪肺炎支原体(Mycoplasma hyopneumonia,Mhp)引起的一种慢性呼吸道传染病,该病给养猪业造成了巨大的经济损失。疫苗接种是目前减轻或预防由猪肺炎支原体感染引发经济损失的主要手段。对猪支原体肺炎基因工程疫苗近年来的研究进展进行综述,主要包括黏附因子相关疫苗、核苷酸还原酶相关疫苗、DNA疫苗、表达文库疫苗和肽疫苗等,最后对基因工程疫苗研究工作的继续开展提供了建议。
Mycoplasmal pneumoniae of swine( MPS) is a chronic respiratory infectious disease caused by Mycoplasma hyopneumonia( Mhp),thus causes huge losses to the pig industry. At present,vaccination is the main means to reduce or prevent the economic losses caused by Mycoplasma pneumoniae. The research progress of gene engineering vaccine of Mycoplasmal pneumoniae of swine in recent years is discussed,mainly includes adhesion factors related vaccines,ribonucleotide reductase related vaccines,DNA vaccines,expression library vaccines and peptide vaccines,etc. Finally,suggestions for the development of genetic engineering vaccines are proposed.
Mycoplasmal pneumoniae of swine( MPS) is a chronic respiratory infectious disease caused by Mycoplasma hyopneumonia( Mhp),thus causes huge losses to the pig industry. At present,vaccination is the main means to reduce or prevent the economic losses caused by Mycoplasma pneumoniae. The research progress of gene engineering vaccine of Mycoplasmal pneumoniae of swine in recent years is discussed,mainly includes adhesion factors related vaccines,ribonucleotide reductase related vaccines,DNA vaccines,expression library vaccines and peptide vaccines,etc. Finally,suggestions for the development of genetic engineering vaccines are proposed.
引文
[1]Wang H,Feng Z,Wu Y,et al.The effects of Mycoplasma hyopneumoniae on porcine circovirus type 2 replication in vitro PK-15 cells.Res Vet Sci,2016,105(4):56-61.
[2]曹培丽,李媛,陈超,等.猪肺炎支原体P52蛋白的原核表达及抗血清制备.中国预防兽医学报,2009,31(7):572-576.Cao P L,Li Y,Chen C,et al.Expression of Mycoplasma hyopneumoniae P52 protein and preparation of the rabbit antisera against P52 protein.Chinese Journal of Preventive Veterinary Medicine,2009,31(7):572-576.
[3]Garcia-Morante B,Segales J,Fraile L,et al.Potential use of local and systemic humoral immune response parameters to forecast Mycoplasma hyopneumoniae associated lung lesions.PLo S One,2017,12(4):e0175034.
[4]施尧.猪支原体肺炎疫苗研究进展.养猪,2013,3:93-95.Shi Y.Research progress of vaccine of Mycoplasma pneumonia.Swine Production,2013,3:93-95.
[5]Fisch A,Marchioro S B,Gomes C K,et al.Commercial bacterins did not induce detectable levels of antibodies in mice against Mycoplasma hyopneumoniae antigens strongly recognized by swine immune system.Trials in Vaccinology,2016,5:32-37.
[6]Zhang Q,Young T F,Ross R F.Identification and characterization of a Mycoplasma hyopneumoniae adhesin.Infect Immun,1995,63(3):1013-1019.
[7]刘茂军,邵国青,张映,等.猪肺炎支原体P97基因抗原决定簇R1区的克隆与表达.江苏农业学报,2005,21(3):207-211.Liu M J,Shao G Q,Zhang Y,et al.Cloning and expressing of R1 region of P97 gene in Mycoplasma hyopneumoniae.Jiangsu Journal of Agricultural Sciences,2005,21(3):207-211.
[8]Conceicao F R,Moreira A N,Dellagostin O A.A recombinant chimera composed of R1 repeat region of Mycoplasma hyopneumoniae P97 adhesin with Escherichia coli heat-labile enterotoxin B subunit elicits immune response in mice.Vaccine,2006,24(29):5734-5743.
[9]卢会英,沈青春,宁宜宝.猪肺炎支原体p97 R1区基因和大肠杆菌LTB基因的重组和表达.中国兽医杂志,2010,46(4):3-6.Lu H Y,Shen Q C,Ning Y B.The recombination and expression of R1 region of Mycoplasma hyopneumoniae p97 adhesin with Escherichia coli heat-labile enterotoxin B subunit.Chinese Journal of Veterinary Medicine,2010,46(4):3-6.
[10]Marchioro S B,Fisch A,Gomes C K,et al.Local and systemic immune responses induced by a recombinant chimeric protein containing Mycoplasma hyopneumoniae antigens fused to the B subunit of Escherichia coli heat-labile enterotoxin LTB.Vet Microbiol,2014,173(1):166-171.
[11]Barate A K,Cho Y,Truong Q L,et al.Immunogenicity of IMS1113 plus soluble subunit and chimeric proteins containing Mycoplasma hyopneumoniae P97 C-terminal repeat regions.FEMS Microbiol Lett,2014,352(2):213-220.
[12]Okamba F R,Arella M,Music N,et al.Potential use of a recombinant replication-defective adenovirus vector carrying the C-terminal portion of the P97 adhesin protein as a vaccine against Mycoplasma hyopneumoniae in swine.Vaccine,2010,28(30):4802-4809.
[13]Tassis P D,Tsakmakidis I,Papatsiros V G,et al.A randomized controlled study on the efficacy of a novel combination vaccine against enzootic pneumonia(Mycoplasma hyopneumoniae)and porcine Circovirus type 2(PCV2)in the presence of strong maternally derived PCV2 immunity in pigs.BMC Vet Res,2017,13(1):91.
[14]Jorge S,de Oliveira N R,Marchioro S B,et al.The Mycoplasma hyopneumoniae recombinant heat shock protein P42 induces an immune response in pigs under field conditions.Comp Immunol Microbiol Infect Dis,2014,37(4):229-236.
[15]Lee S H,Lee S,Chae C,et al.A recombinant chimera comprising the R1 and R2 repeat regions of M.hyopneumoniae P97 and the N-terminal region of A.pleuropneumoniae Apx III elicits immune responses.BMC Vet Res,2014,10(1):43.
[16]Shimoji Y,Oishi E,Muneta Y,et al.Vaccine efficacy of the attenuated Erysipelothrix rhusiopathiae YS-19 expressing a recombinant protein of Mycoplasma hyopneumoniae P97 adhesin against mycoplasmal pneumonia of swine.Vaccine,2003,21(5):532-537.
[17]Petersen A C,Oneal D C,Seibel J R,et al.Cross reactivity among the swine mycoplasmas as identified by protein microarray.Vet Microbiol,2016,192(8):204-212.
[18]Jeong J,Park C,Choi K,et al.A new single-dose bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae elicits protective immunity and improves growth performance under field conditions.Vet Microbiol,2016,182(1):178-186.
[19]de Oliveira N R,Jorge S,Gomes C K,et al.A novel chimeric protein composed of recombinant Mycoplasma hyopneumoniae antigens as a vaccine candidate evaluated in mice.Vet Microbiol,2017,201(3):146-153.
[20]Galli V,Simionatto S,Marchioro S B,et al.Immunisation of mice with Mycoplasma hyopneumoniae antigens P37,P42,P46and P95 delivered as recombinant subunit or DNA vaccines.Vaccine,2012,31(1):135-140.
[21]Zou H Y,Liu X J,Ma F Y,et al.Attenuated Actinobacillus pleuropneumoniae as a bacterial vector for expression of Mycoplasma hyopneumoniae P36 gene.J Gene Med,2011,13(4):221-229.
[22]Burnett T A,Dinkla K,Rohde M,et al.P159 is a proteolytically processed,surface adhesin of Mycoplasma hyopneumoniae:defined domains of P159 bind heparin and promote adherence to eukaryote cells.Mol Microbiol,2006,60(3):669-686.
[23]Fagan P K,Djordjevic S P,Eamens G J,et al.Molecular characterization of a ribonucleotide reductase(nrd F)gene fragment of Mycoplasma hyopneumoniae and assessment of the recombinant product as an experimental vaccine for enzootic pneumonia.Infect Immun,1996,64(3):1060-1064.
[24]Fagan P K,Djordjevic S P,Chin J,et al.Oral immunization of mice with attenuated Salmonella typhimurium aro A expressing a recombinant Mycoplasma hyopneumoniae antigen(Nrd F).Infect Immun,1997,65(6):2502-2507.
[25]Fagan P K,Walker M J,Chin J,et al.Oral immunization of swine with attenuated Salmonella typhimurium aro A SL3261expressing a recombinant antigen of Mycoplasma hyopneumoniae(Nrd F)primes the immune system for a Nrd F specific secretory Ig A response in the lungs.Microb Pathog,2001,30(2):101-110.
[26]Chen A Y,Fry S R,Forbes-Faulkner J,et al.Comparative immunogenicity of M.hyopneumoniae Nrd F encoded in different expression systems delivered orally via attenuated S.typhimurium aro A in mice.Vet Microbiol,2006,114(3):252-259.
[27]Maes D,Segales J,Meyns T,et al.Control of Mycoplasma hyopneumoniae infections in pigs.Vet Microbiol,2008,126(4):297-309.
[28]Marchioro S B,Maes D,Flahou B,et al.Local and systemic immune responses in pigs intramuscularly injected with an inactivated Mycoplasma hyopneumoniae vaccine.Vaccine,2013,31(9):1305-1311.
[29]Simionatto S,Marchioro S B,Maes D,et al.Mycoplasma hyopneumoniae:from disease to vaccine development.Vet Microbiol,2013,165(3):234-242.
[30]Thacker E L,Thacker B J,Kuhn M,et al.Evaluation of local and systemic immune responses induced by intramuscular injection of a Mycoplasma hyopneumoniae bacterin to pigs.Am J Vet Res,2000,61(11):1384-1389.
[31]Babiuk L A.Vaccination:a management tool in veterinary medicine.Vet J,2002,164(3):188-201.
[32]Chen Y L,Wang S N,Yang W J,et al.Expression and immunogenicity of Mycoplasma hyopneumoniae heat shock protein antigen P42 by DNA vaccination.Infect Immun,2003,71(3):1155-1160.
[33]Chen A Y,Fry S R,Daggard G E,et al.Evaluation of immune response to recombinant potential protective antigens of Mycoplasma hyopneumoniae delivered as cocktail DNA and/or recombinant protein vaccines in mice.Vaccine,2008,26(34):4372-4378.
[34]Virginio V G,Gonchoroski T,Paes J A,et al.Immune responses elicited by Mycoplasma hyopneumoniae recombinant antigens and DNA constructs with potential for use in vaccination against porcine enzootic pneumonia.Vaccine,2014,32(44):5832-5838.
[35]Talaat A M,Stemke-Hale K.Expression library immunization:a road map for discovery of vaccines against infectious diseases.Infect Immun,2005,73(11):7089-7098.
[36]Moore R J,Lenghaus C,Sheedy S A,et al.Improved vectors for expression library immunization--application to Mycoplasma hyopneumoniae infection in pigs.Vaccine,2001,20(1):115-120.
[37]Razin S,Yogev D,Naot Y.Molecular biology and pathogenicity of mycoplasmas.Microbiol Mol Biol Rev,1998,62(4):1094-1156.
[38]King K W,Faulds D H,Rosey E L,et al.Characterization of the gene encoding Mhp1 from Mycoplasma hyopneumoniae and examination of Mhp1’s vaccine potential.Vaccine,1997,15(1):25-35.
[39]Yang W J,Lai J F,Peng K C,et al.Epitope mapping of Mycoplasma hyopneumoniae using phage displayed peptide libraries and the immune responses of the selected phagotopes.J Immunol Methods,2005,304(1):15-29.
[40]Ishag H Z,Wu Y Z,Liu M J,et al.In vitro protective efficacy of lithium chloride against Mycoplasma hyopneumoniae infection.Res Vet Sci,2016,106(6):93-96.
[41]Virginio V G,Bandeira N C,Leal F M,et al.Assessment of the adjuvant activity of mesoporous silica nanoparticles in recombinant Mycoplasma hyopneumoniae antigen vaccines.Heliyon,2017,3(1):e00225.
[42]Michiels A,Vranckx K,Piepers S,et al.Impact of diversity of Mycoplasma hyopneumoniae strains on lung lesions in slaughter pigs.Vet Res,2017,48(1):2-14.
[43]Chae C.Porcine respiratory disease complex:Interaction of vaccination and porcine circovirus type 2,porcine reproductive and respiratory syndrome virus,and Mycoplasma hyopneumoniae.Vet J,2016,212(2):1-6.
[2]曹培丽,李媛,陈超,等.猪肺炎支原体P52蛋白的原核表达及抗血清制备.中国预防兽医学报,2009,31(7):572-576.Cao P L,Li Y,Chen C,et al.Expression of Mycoplasma hyopneumoniae P52 protein and preparation of the rabbit antisera against P52 protein.Chinese Journal of Preventive Veterinary Medicine,2009,31(7):572-576.
[3]Garcia-Morante B,Segales J,Fraile L,et al.Potential use of local and systemic humoral immune response parameters to forecast Mycoplasma hyopneumoniae associated lung lesions.PLo S One,2017,12(4):e0175034.
[4]施尧.猪支原体肺炎疫苗研究进展.养猪,2013,3:93-95.Shi Y.Research progress of vaccine of Mycoplasma pneumonia.Swine Production,2013,3:93-95.
[5]Fisch A,Marchioro S B,Gomes C K,et al.Commercial bacterins did not induce detectable levels of antibodies in mice against Mycoplasma hyopneumoniae antigens strongly recognized by swine immune system.Trials in Vaccinology,2016,5:32-37.
[6]Zhang Q,Young T F,Ross R F.Identification and characterization of a Mycoplasma hyopneumoniae adhesin.Infect Immun,1995,63(3):1013-1019.
[7]刘茂军,邵国青,张映,等.猪肺炎支原体P97基因抗原决定簇R1区的克隆与表达.江苏农业学报,2005,21(3):207-211.Liu M J,Shao G Q,Zhang Y,et al.Cloning and expressing of R1 region of P97 gene in Mycoplasma hyopneumoniae.Jiangsu Journal of Agricultural Sciences,2005,21(3):207-211.
[8]Conceicao F R,Moreira A N,Dellagostin O A.A recombinant chimera composed of R1 repeat region of Mycoplasma hyopneumoniae P97 adhesin with Escherichia coli heat-labile enterotoxin B subunit elicits immune response in mice.Vaccine,2006,24(29):5734-5743.
[9]卢会英,沈青春,宁宜宝.猪肺炎支原体p97 R1区基因和大肠杆菌LTB基因的重组和表达.中国兽医杂志,2010,46(4):3-6.Lu H Y,Shen Q C,Ning Y B.The recombination and expression of R1 region of Mycoplasma hyopneumoniae p97 adhesin with Escherichia coli heat-labile enterotoxin B subunit.Chinese Journal of Veterinary Medicine,2010,46(4):3-6.
[10]Marchioro S B,Fisch A,Gomes C K,et al.Local and systemic immune responses induced by a recombinant chimeric protein containing Mycoplasma hyopneumoniae antigens fused to the B subunit of Escherichia coli heat-labile enterotoxin LTB.Vet Microbiol,2014,173(1):166-171.
[11]Barate A K,Cho Y,Truong Q L,et al.Immunogenicity of IMS1113 plus soluble subunit and chimeric proteins containing Mycoplasma hyopneumoniae P97 C-terminal repeat regions.FEMS Microbiol Lett,2014,352(2):213-220.
[12]Okamba F R,Arella M,Music N,et al.Potential use of a recombinant replication-defective adenovirus vector carrying the C-terminal portion of the P97 adhesin protein as a vaccine against Mycoplasma hyopneumoniae in swine.Vaccine,2010,28(30):4802-4809.
[13]Tassis P D,Tsakmakidis I,Papatsiros V G,et al.A randomized controlled study on the efficacy of a novel combination vaccine against enzootic pneumonia(Mycoplasma hyopneumoniae)and porcine Circovirus type 2(PCV2)in the presence of strong maternally derived PCV2 immunity in pigs.BMC Vet Res,2017,13(1):91.
[14]Jorge S,de Oliveira N R,Marchioro S B,et al.The Mycoplasma hyopneumoniae recombinant heat shock protein P42 induces an immune response in pigs under field conditions.Comp Immunol Microbiol Infect Dis,2014,37(4):229-236.
[15]Lee S H,Lee S,Chae C,et al.A recombinant chimera comprising the R1 and R2 repeat regions of M.hyopneumoniae P97 and the N-terminal region of A.pleuropneumoniae Apx III elicits immune responses.BMC Vet Res,2014,10(1):43.
[16]Shimoji Y,Oishi E,Muneta Y,et al.Vaccine efficacy of the attenuated Erysipelothrix rhusiopathiae YS-19 expressing a recombinant protein of Mycoplasma hyopneumoniae P97 adhesin against mycoplasmal pneumonia of swine.Vaccine,2003,21(5):532-537.
[17]Petersen A C,Oneal D C,Seibel J R,et al.Cross reactivity among the swine mycoplasmas as identified by protein microarray.Vet Microbiol,2016,192(8):204-212.
[18]Jeong J,Park C,Choi K,et al.A new single-dose bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae elicits protective immunity and improves growth performance under field conditions.Vet Microbiol,2016,182(1):178-186.
[19]de Oliveira N R,Jorge S,Gomes C K,et al.A novel chimeric protein composed of recombinant Mycoplasma hyopneumoniae antigens as a vaccine candidate evaluated in mice.Vet Microbiol,2017,201(3):146-153.
[20]Galli V,Simionatto S,Marchioro S B,et al.Immunisation of mice with Mycoplasma hyopneumoniae antigens P37,P42,P46and P95 delivered as recombinant subunit or DNA vaccines.Vaccine,2012,31(1):135-140.
[21]Zou H Y,Liu X J,Ma F Y,et al.Attenuated Actinobacillus pleuropneumoniae as a bacterial vector for expression of Mycoplasma hyopneumoniae P36 gene.J Gene Med,2011,13(4):221-229.
[22]Burnett T A,Dinkla K,Rohde M,et al.P159 is a proteolytically processed,surface adhesin of Mycoplasma hyopneumoniae:defined domains of P159 bind heparin and promote adherence to eukaryote cells.Mol Microbiol,2006,60(3):669-686.
[23]Fagan P K,Djordjevic S P,Eamens G J,et al.Molecular characterization of a ribonucleotide reductase(nrd F)gene fragment of Mycoplasma hyopneumoniae and assessment of the recombinant product as an experimental vaccine for enzootic pneumonia.Infect Immun,1996,64(3):1060-1064.
[24]Fagan P K,Djordjevic S P,Chin J,et al.Oral immunization of mice with attenuated Salmonella typhimurium aro A expressing a recombinant Mycoplasma hyopneumoniae antigen(Nrd F).Infect Immun,1997,65(6):2502-2507.
[25]Fagan P K,Walker M J,Chin J,et al.Oral immunization of swine with attenuated Salmonella typhimurium aro A SL3261expressing a recombinant antigen of Mycoplasma hyopneumoniae(Nrd F)primes the immune system for a Nrd F specific secretory Ig A response in the lungs.Microb Pathog,2001,30(2):101-110.
[26]Chen A Y,Fry S R,Forbes-Faulkner J,et al.Comparative immunogenicity of M.hyopneumoniae Nrd F encoded in different expression systems delivered orally via attenuated S.typhimurium aro A in mice.Vet Microbiol,2006,114(3):252-259.
[27]Maes D,Segales J,Meyns T,et al.Control of Mycoplasma hyopneumoniae infections in pigs.Vet Microbiol,2008,126(4):297-309.
[28]Marchioro S B,Maes D,Flahou B,et al.Local and systemic immune responses in pigs intramuscularly injected with an inactivated Mycoplasma hyopneumoniae vaccine.Vaccine,2013,31(9):1305-1311.
[29]Simionatto S,Marchioro S B,Maes D,et al.Mycoplasma hyopneumoniae:from disease to vaccine development.Vet Microbiol,2013,165(3):234-242.
[30]Thacker E L,Thacker B J,Kuhn M,et al.Evaluation of local and systemic immune responses induced by intramuscular injection of a Mycoplasma hyopneumoniae bacterin to pigs.Am J Vet Res,2000,61(11):1384-1389.
[31]Babiuk L A.Vaccination:a management tool in veterinary medicine.Vet J,2002,164(3):188-201.
[32]Chen Y L,Wang S N,Yang W J,et al.Expression and immunogenicity of Mycoplasma hyopneumoniae heat shock protein antigen P42 by DNA vaccination.Infect Immun,2003,71(3):1155-1160.
[33]Chen A Y,Fry S R,Daggard G E,et al.Evaluation of immune response to recombinant potential protective antigens of Mycoplasma hyopneumoniae delivered as cocktail DNA and/or recombinant protein vaccines in mice.Vaccine,2008,26(34):4372-4378.
[34]Virginio V G,Gonchoroski T,Paes J A,et al.Immune responses elicited by Mycoplasma hyopneumoniae recombinant antigens and DNA constructs with potential for use in vaccination against porcine enzootic pneumonia.Vaccine,2014,32(44):5832-5838.
[35]Talaat A M,Stemke-Hale K.Expression library immunization:a road map for discovery of vaccines against infectious diseases.Infect Immun,2005,73(11):7089-7098.
[36]Moore R J,Lenghaus C,Sheedy S A,et al.Improved vectors for expression library immunization--application to Mycoplasma hyopneumoniae infection in pigs.Vaccine,2001,20(1):115-120.
[37]Razin S,Yogev D,Naot Y.Molecular biology and pathogenicity of mycoplasmas.Microbiol Mol Biol Rev,1998,62(4):1094-1156.
[38]King K W,Faulds D H,Rosey E L,et al.Characterization of the gene encoding Mhp1 from Mycoplasma hyopneumoniae and examination of Mhp1’s vaccine potential.Vaccine,1997,15(1):25-35.
[39]Yang W J,Lai J F,Peng K C,et al.Epitope mapping of Mycoplasma hyopneumoniae using phage displayed peptide libraries and the immune responses of the selected phagotopes.J Immunol Methods,2005,304(1):15-29.
[40]Ishag H Z,Wu Y Z,Liu M J,et al.In vitro protective efficacy of lithium chloride against Mycoplasma hyopneumoniae infection.Res Vet Sci,2016,106(6):93-96.
[41]Virginio V G,Bandeira N C,Leal F M,et al.Assessment of the adjuvant activity of mesoporous silica nanoparticles in recombinant Mycoplasma hyopneumoniae antigen vaccines.Heliyon,2017,3(1):e00225.
[42]Michiels A,Vranckx K,Piepers S,et al.Impact of diversity of Mycoplasma hyopneumoniae strains on lung lesions in slaughter pigs.Vet Res,2017,48(1):2-14.
[43]Chae C.Porcine respiratory disease complex:Interaction of vaccination and porcine circovirus type 2,porcine reproductive and respiratory syndrome virus,and Mycoplasma hyopneumoniae.Vet J,2016,212(2):1-6.