微生物介导的恶性疟原虫PfMSP-1疫苗的研制现状
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摘要
恶性疟原虫引起的恶性疟是一种严重危害人类健康的寄生虫病,采用疫苗防治该病是当前研究的热点领域之一。PfMSP-1抗原是一种有效的疫苗候选分子,鼠伤寒沙门菌、卡介苗、酵母菌、根癌农杆菌、嗜热四膜菌、腺病毒、牛痘病毒和杆状病毒等微生物经过改造后均可成为有希望的疫苗载体。本文综述了重组鼠伤寒沙门菌(rSt-PfMSP-1和rSt-PfMSP-1_(19))、重组BCG疫苗(rBCG-PfMSP-1c和rBCGPfMSP-1_(19))、重组酵母菌(rPp-PfMSP-1)、重组根癌农杆菌(rAt-PfMSP-1_(42)、rAt-PfMSP4/5和rAtPf38)、重组嗜热四膜菌(rTt-PfMSP-1_(19))、重组腺病毒(rAd5-PfMSP-1_(42)和rChAd63-PfMSP-1)、重组牛痘病毒(rVV-PfMSP-1和rVV-PfHGFSP)以及重组杆状病毒(rBDES-PfMSP-1_(19))的构建及其免疫机制的研制现状。
Falciparum malaria caused by Plasmodium falciparum is one type of parasitic diseases seriously endangering human health.To control this parasite by use of vaccine has recently become a hotspot of research.PfMSP-1 antigen is an effective candidate molecule of vaccines,and many microorganisms such as Salmonella typhimurium,Bacillus calmette-Guerin,Pichia pastoris,Agrobacterium tumefaciens,Tetrahymena thermophila,Adenovirus,Vaccinia virus and Baculovirus may become hopeful vehicles after they are modified.This article reviews the current status of the research on the construction and immune mechanisms of these vaccines including rSt-PfMSP-1,rSt-PfMSP-1_(19),rBCG-PfMSP-1 c,rBCG-PfMSP-1_(19),rPpPfMSP-1,rAt-PfMSP-1_(42),rAt-PfMSP4/5,rAt-Pf38,rTt-PfMSP-1_(19),rAd5-PfMSP-142,rChAd63-PfMSP-1,and rBDES-PfMSP-1_(19).
Falciparum malaria caused by Plasmodium falciparum is one type of parasitic diseases seriously endangering human health.To control this parasite by use of vaccine has recently become a hotspot of research.PfMSP-1 antigen is an effective candidate molecule of vaccines,and many microorganisms such as Salmonella typhimurium,Bacillus calmette-Guerin,Pichia pastoris,Agrobacterium tumefaciens,Tetrahymena thermophila,Adenovirus,Vaccinia virus and Baculovirus may become hopeful vehicles after they are modified.This article reviews the current status of the research on the construction and immune mechanisms of these vaccines including rSt-PfMSP-1,rSt-PfMSP-1_(19),rBCG-PfMSP-1 c,rBCG-PfMSP-1_(19),rPpPfMSP-1,rAt-PfMSP-1_(42),rAt-PfMSP4/5,rAt-Pf38,rTt-PfMSP-1_(19),rAd5-PfMSP-142,rChAd63-PfMSP-1,and rBDES-PfMSP-1_(19).
引文
[1]Clyde DF,McCarthy VC,Miller RM,et al.Specificity of protection of man immunized against sporozoite-induced falciparum malaria[J].Am J Med Sci,1973,266(3):169-177.
[2]Rénia L,Grüner AC,Mauduit M,et al.Vaccination against malaria with live parasites[J].Exp Rev Vaccines,2006,5(4):473-481.
[3]MIAO Jun,XUE Caifang,YU Qigui,et al.Construction of a couple of eukaryotic expression recombinants containing the gene fragment of 42kD C-terminal region of Plasmodium falciparum merozoite surface protein 1[J].Chin J Microbiol Immunol,1998,18(3):186-188.(in Chinese)缪军,薛采芳,喻启桂,等.恶性疟原虫裂殖子表面蛋白1羧基端编码基因真核表达重组克隆的构建[J].中华微生物学和免疫学杂志,1998,18(3):186-188.
[4]MIAO Jun,LI Xun,XUE Caifang,et al.Humoral immune response in mice to hybrid nucleic acid vaccines containing Plasmodium falciparum merozoite surface protein 1block 17-based gene[J].Chin J Parasitol Parasit Dis,1999,17(5):302-309.(in Chinese)缪军,李珣,薛采芳,等.以恶性疟原虫裂殖子表面蛋白1的17区片段基因为基础的复合核酸疫苗诱导小鼠体液免疫反应的研究[J].中国寄生虫学与寄生虫病杂志,1999,17(5):302-309.
[5]Stowers AW,Chen LL,Zhang Y,et al.A recombinant vaccine expressed in the milk of transgenic mice protects Aotus monkeys from a lethal challenge with Plasmodium falciparum[J].Proc Natl Acad Sci U S A,2002,99(1):339-344.
[6]LI Shumei,LI Xun,XUE Caifang,et al.DNA/MVA combined immunization:Antibody response to Plasmodium falciparum merozoite surface protein 1in mice[J].Chin J Parasitol Parasit Dis,2005,23(2):93-96.(in Chinese)李淑梅,李珣,薛采芳,等.恶性疟原虫裂殖子表面蛋白1DNA与改良痘苗病毒组合疫苗诱导小鼠抗体应答[J].中国寄生虫学与寄生虫病杂志,2005,23(2):93-96.
[7]QIAN Feng,GUAN Weibin,FANG Jun,et al.Construction of recombinant attenuated Salmonella typhimurium vaccine strain expressing Plasmodium falciparum merozoite surface protein 1fragments[J].Chin J Infect Dis,2000,18(3):186-189.(in Chinese)钱锋,管惟滨,方军,等.表达恶性疟原虫裂殖子表面蛋白-1片段的减毒鼠伤寒杆菌的构建[J].中华传染病杂志,2000,18(3):186-189.
[8]QIAN Feng,GUAN Weibin,FANG Jun,et al.Immune response of BALB/c mice inoculated with recombinant attenuated Salmonella typhimurium with gene fragment of Plasmodium falciparum[J].Chin J Nat,2000,22(6):366-367.(in Chinese)钱锋,管惟滨,方军.含恶性疟原虫基因片段的重组减毒伤寒杆菌的免疫效果[J].自然杂志,2000,22(6):366-367.
[9]Wu SG,Beier M,Sztein MB,et al.Construction and immunogenicity in mice of attenuated Salmonella typhi expressing Plasmodium falciparum merozoite surface protein 1(MSP-1)fused to tetanus toxin fragment C[J].J Biotechnol,2000,83(1):125-135.
[10]Cirillo JD,Stover CK,Bloom BR,et al.Bacterial vaccine vectors and bacillus Calmette-Guérin[J].Clin Infect Dis,1995,20(4):1001-1009.
[11]Matsuo K,Yamaguchi R,Yamazaki A,et al.Establishment of a foreign antigen secretion system in Mycobacteria[J].Infect Immun,1990,58(12):4049-4054.
[12]Rapeah S,Dhaniah M,Nurul AA,et al.Phagocytic activity and pro-inflammatory cytokines production by the murine macrophage cell line J774A.1stimulated by a recombinant BCG(rBCG)expressing the MSP1-C of Plasmodium falciparum[J].Trop Biomed,2010,27(3):461-469.
[13]Nurul AA,Rapeah S,Norazmi MN.Plasmodium falciparum19kDa of merozoite surface protein-1(MSP-119)expressed in Mycobacterium bovis bacille Calmette Guerin(BCG)is reactive with an inhibitory but not a blocking monoclonal antibody[J].Trop Biomed,2010,27(1):60-67.
[14]Nurul AA,Norazmi MN.Immunogenicity and in vitro protective efficacy of recombinant Mycobacterium bovis,bacille Calmette Guerin(rBCG)expressing the 19kDa merozoite surface protein-1(MSP-119)antigen of Plasmodium falciparum[J].Parasitol Res,2011,108:887-897.
[15]ZHANG Dongmei,PAN Weiqing,LU Deru.Production of the major merozoite surface protein 1(MSP1)of Plasmodium falciparumin Pichia pastoris[J].Chin J Biotechnol,2000,16(6):723-726.(in Chinese)张冬梅,潘卫庆,陆德如.恶性疟裂殖子表面蛋白1合成基因在毕赤酵母中的表达[J].生物工程学报,2000,16(6):723-726.
[16]Zhang ZG,Zhao HM,Gong M.High level expression and purification of 1C-terminal fragment of merozoite surface protein of Plasmodium falciparumin Pichia pastoris[J].Chin J Zoonoses,2005,21(12):1047-1051.
[17]Fraley RT,Rogers SG,Horsch RB,et al.Expression of bacterial genes in plant cells[J].Proc Natl Acad Sci U S A,1983,80(15):4803-4807.
[18]Fraley RT,Rogers SG,Horsch RB,et al.Expression of bacterial genes in plant cells[J].Proc Natl Acad Sci U S A.1983,80(15):4803-4807.
[19]CHEN Qin,LIANG Wanqi,QIAN Binjun,et al.Introduction of Plasmodium falciparun C-terminal region of the merozoite surface protein gene into the chloroplast of tobacco[J].Chin JParasitol Parasit Dis,2008,26(4):263-267.(in Chinese)陈勤,梁婉琪,钱炳俊,等.恶性疟原虫裂殖子表面蛋白1C末端基因导入烟草叶绿体的研究[J].中国寄生虫学与寄生虫病杂志,2008,26(4):263-267.
[20]Chen Q,Liang W,Qian F,et al.Rice-produced MSP142of Plasmodium falciparumelicits antibodies that inhibit parasite growth in vitro[J].Parasite Immunol,2016,38(10):635-641.
[21]Lau OS,Ng DW,Chang WW,et al.Production of the 42kDa fragment of Plasmodium falciparum merozoite surface protein1,a leading malaria vaccine antigen,in Arabidopsis thaliana seeds[J].Plant Biotechnol J,2010,8(9):994-1004.
[22]Webster DE,Wang L,Mulcair M,et al.Production and characterization of an orally immunogenic Plasmodium antigen in plants using a virus-based expression system[J].Plant Biotech J,2009,7(9):846-855.
[23]Feller T,Thom P,Koch N,et al.Plant-based production of recombinant Plasmodium surface protein pf38and evaluation of its potential as a vaccine candidate[J].PLoS One,2013,8(11):e79920.
[24]Cowan GJ,Bockau U,Eleni-Muus J,et al.A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila[J].PLoS One,2014,9(1):e87198.
[25]Schuldt NJ,Amalfitano A.Malaria vaccines:Focus on adenovirus based vectors[J].Vaccine,2012,30(35):5191-5198.
[26]Bruder JT,Stefaniak ME,Patterson NB,et al.Adenovectors induce functional antibodies capable of potent inhibition of blood stage malaria parasite growth[J].Vaccine,2010,28(18):3201-3210.
[27]Sheehy SH,Duncan CJ,Elias SC,et al.Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen MSP1in ChAd63and MVA vaccine vectors[J].Mol Ther,2011,19(12):2269-2276.
[28]Sutter G,Staib C.Vaccinia vectors as candidate vaccines:The development of modified vaccinia virus Ankara for antigen delivery[J].Curr Drug Targets Infect Disord,2003,3(3):263-271.
[29]Tine JA,Lanar DE,Smith DM,et al.NYVAC-Pf7:A poxvirus-vectored,multiantigen,multistage vaccine candidate for Plasmodium falciparum malaria[J].Infect Immun,1996,64(9):3833-3844.
[30]YAO Lang,LI Yingjie,LI Ming.Cell-mediated and humoral immune responses in mice induced by a malaria DNA vaccine from a hybrid gene of antigen for Plasmodium falciparum[J].Chin J Parasit Dis Con,2002,15(6):342-345.(in Chinese)姚朗,李英杰,李明.恶性疟原虫复合抗原DNA疫苗诱导小鼠的细胞免疫及体液免疫应答[J].中国寄生虫病防治杂志,2002,15(6):342-345.
[31]Dong W,Li M,Bi H,t al.Assessment of a vaccinia virus vectored multi-epitope live vaccine candidate for Plasmodium falciparum[J].Int J Parasitol,2001,31(1):57-62.
[32]Arnot DE,Cavanagh DR,Remarque EJ,et al.Comparative testing of six antigen-based malaria vaccine candidates directed toward merozoite-stage Plasmodium falciparum[J].Clin Vaccine Immunol,2008,15(9):1345-1355.
[33]LI Wengui,CHEN Yatang.Current status of research on vector-mediated MIC vaccine against Toxaplasma gondii[J].Chin J Microecol,2017,29(6):735-738.(in Chinese)李文桂,陈雅棠.载体介导的刚地弓形虫MIC疫苗的研制现状[J].中国微生态学杂志,2017,29(6):735-738.
[2]Rénia L,Grüner AC,Mauduit M,et al.Vaccination against malaria with live parasites[J].Exp Rev Vaccines,2006,5(4):473-481.
[3]MIAO Jun,XUE Caifang,YU Qigui,et al.Construction of a couple of eukaryotic expression recombinants containing the gene fragment of 42kD C-terminal region of Plasmodium falciparum merozoite surface protein 1[J].Chin J Microbiol Immunol,1998,18(3):186-188.(in Chinese)缪军,薛采芳,喻启桂,等.恶性疟原虫裂殖子表面蛋白1羧基端编码基因真核表达重组克隆的构建[J].中华微生物学和免疫学杂志,1998,18(3):186-188.
[4]MIAO Jun,LI Xun,XUE Caifang,et al.Humoral immune response in mice to hybrid nucleic acid vaccines containing Plasmodium falciparum merozoite surface protein 1block 17-based gene[J].Chin J Parasitol Parasit Dis,1999,17(5):302-309.(in Chinese)缪军,李珣,薛采芳,等.以恶性疟原虫裂殖子表面蛋白1的17区片段基因为基础的复合核酸疫苗诱导小鼠体液免疫反应的研究[J].中国寄生虫学与寄生虫病杂志,1999,17(5):302-309.
[5]Stowers AW,Chen LL,Zhang Y,et al.A recombinant vaccine expressed in the milk of transgenic mice protects Aotus monkeys from a lethal challenge with Plasmodium falciparum[J].Proc Natl Acad Sci U S A,2002,99(1):339-344.
[6]LI Shumei,LI Xun,XUE Caifang,et al.DNA/MVA combined immunization:Antibody response to Plasmodium falciparum merozoite surface protein 1in mice[J].Chin J Parasitol Parasit Dis,2005,23(2):93-96.(in Chinese)李淑梅,李珣,薛采芳,等.恶性疟原虫裂殖子表面蛋白1DNA与改良痘苗病毒组合疫苗诱导小鼠抗体应答[J].中国寄生虫学与寄生虫病杂志,2005,23(2):93-96.
[7]QIAN Feng,GUAN Weibin,FANG Jun,et al.Construction of recombinant attenuated Salmonella typhimurium vaccine strain expressing Plasmodium falciparum merozoite surface protein 1fragments[J].Chin J Infect Dis,2000,18(3):186-189.(in Chinese)钱锋,管惟滨,方军,等.表达恶性疟原虫裂殖子表面蛋白-1片段的减毒鼠伤寒杆菌的构建[J].中华传染病杂志,2000,18(3):186-189.
[8]QIAN Feng,GUAN Weibin,FANG Jun,et al.Immune response of BALB/c mice inoculated with recombinant attenuated Salmonella typhimurium with gene fragment of Plasmodium falciparum[J].Chin J Nat,2000,22(6):366-367.(in Chinese)钱锋,管惟滨,方军.含恶性疟原虫基因片段的重组减毒伤寒杆菌的免疫效果[J].自然杂志,2000,22(6):366-367.
[9]Wu SG,Beier M,Sztein MB,et al.Construction and immunogenicity in mice of attenuated Salmonella typhi expressing Plasmodium falciparum merozoite surface protein 1(MSP-1)fused to tetanus toxin fragment C[J].J Biotechnol,2000,83(1):125-135.
[10]Cirillo JD,Stover CK,Bloom BR,et al.Bacterial vaccine vectors and bacillus Calmette-Guérin[J].Clin Infect Dis,1995,20(4):1001-1009.
[11]Matsuo K,Yamaguchi R,Yamazaki A,et al.Establishment of a foreign antigen secretion system in Mycobacteria[J].Infect Immun,1990,58(12):4049-4054.
[12]Rapeah S,Dhaniah M,Nurul AA,et al.Phagocytic activity and pro-inflammatory cytokines production by the murine macrophage cell line J774A.1stimulated by a recombinant BCG(rBCG)expressing the MSP1-C of Plasmodium falciparum[J].Trop Biomed,2010,27(3):461-469.
[13]Nurul AA,Rapeah S,Norazmi MN.Plasmodium falciparum19kDa of merozoite surface protein-1(MSP-119)expressed in Mycobacterium bovis bacille Calmette Guerin(BCG)is reactive with an inhibitory but not a blocking monoclonal antibody[J].Trop Biomed,2010,27(1):60-67.
[14]Nurul AA,Norazmi MN.Immunogenicity and in vitro protective efficacy of recombinant Mycobacterium bovis,bacille Calmette Guerin(rBCG)expressing the 19kDa merozoite surface protein-1(MSP-119)antigen of Plasmodium falciparum[J].Parasitol Res,2011,108:887-897.
[15]ZHANG Dongmei,PAN Weiqing,LU Deru.Production of the major merozoite surface protein 1(MSP1)of Plasmodium falciparumin Pichia pastoris[J].Chin J Biotechnol,2000,16(6):723-726.(in Chinese)张冬梅,潘卫庆,陆德如.恶性疟裂殖子表面蛋白1合成基因在毕赤酵母中的表达[J].生物工程学报,2000,16(6):723-726.
[16]Zhang ZG,Zhao HM,Gong M.High level expression and purification of 1C-terminal fragment of merozoite surface protein of Plasmodium falciparumin Pichia pastoris[J].Chin J Zoonoses,2005,21(12):1047-1051.
[17]Fraley RT,Rogers SG,Horsch RB,et al.Expression of bacterial genes in plant cells[J].Proc Natl Acad Sci U S A,1983,80(15):4803-4807.
[18]Fraley RT,Rogers SG,Horsch RB,et al.Expression of bacterial genes in plant cells[J].Proc Natl Acad Sci U S A.1983,80(15):4803-4807.
[19]CHEN Qin,LIANG Wanqi,QIAN Binjun,et al.Introduction of Plasmodium falciparun C-terminal region of the merozoite surface protein gene into the chloroplast of tobacco[J].Chin JParasitol Parasit Dis,2008,26(4):263-267.(in Chinese)陈勤,梁婉琪,钱炳俊,等.恶性疟原虫裂殖子表面蛋白1C末端基因导入烟草叶绿体的研究[J].中国寄生虫学与寄生虫病杂志,2008,26(4):263-267.
[20]Chen Q,Liang W,Qian F,et al.Rice-produced MSP142of Plasmodium falciparumelicits antibodies that inhibit parasite growth in vitro[J].Parasite Immunol,2016,38(10):635-641.
[21]Lau OS,Ng DW,Chang WW,et al.Production of the 42kDa fragment of Plasmodium falciparum merozoite surface protein1,a leading malaria vaccine antigen,in Arabidopsis thaliana seeds[J].Plant Biotechnol J,2010,8(9):994-1004.
[22]Webster DE,Wang L,Mulcair M,et al.Production and characterization of an orally immunogenic Plasmodium antigen in plants using a virus-based expression system[J].Plant Biotech J,2009,7(9):846-855.
[23]Feller T,Thom P,Koch N,et al.Plant-based production of recombinant Plasmodium surface protein pf38and evaluation of its potential as a vaccine candidate[J].PLoS One,2013,8(11):e79920.
[24]Cowan GJ,Bockau U,Eleni-Muus J,et al.A novel malaria vaccine candidate antigen expressed in Tetrahymena thermophila[J].PLoS One,2014,9(1):e87198.
[25]Schuldt NJ,Amalfitano A.Malaria vaccines:Focus on adenovirus based vectors[J].Vaccine,2012,30(35):5191-5198.
[26]Bruder JT,Stefaniak ME,Patterson NB,et al.Adenovectors induce functional antibodies capable of potent inhibition of blood stage malaria parasite growth[J].Vaccine,2010,28(18):3201-3210.
[27]Sheehy SH,Duncan CJ,Elias SC,et al.Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen MSP1in ChAd63and MVA vaccine vectors[J].Mol Ther,2011,19(12):2269-2276.
[28]Sutter G,Staib C.Vaccinia vectors as candidate vaccines:The development of modified vaccinia virus Ankara for antigen delivery[J].Curr Drug Targets Infect Disord,2003,3(3):263-271.
[29]Tine JA,Lanar DE,Smith DM,et al.NYVAC-Pf7:A poxvirus-vectored,multiantigen,multistage vaccine candidate for Plasmodium falciparum malaria[J].Infect Immun,1996,64(9):3833-3844.
[30]YAO Lang,LI Yingjie,LI Ming.Cell-mediated and humoral immune responses in mice induced by a malaria DNA vaccine from a hybrid gene of antigen for Plasmodium falciparum[J].Chin J Parasit Dis Con,2002,15(6):342-345.(in Chinese)姚朗,李英杰,李明.恶性疟原虫复合抗原DNA疫苗诱导小鼠的细胞免疫及体液免疫应答[J].中国寄生虫病防治杂志,2002,15(6):342-345.
[31]Dong W,Li M,Bi H,t al.Assessment of a vaccinia virus vectored multi-epitope live vaccine candidate for Plasmodium falciparum[J].Int J Parasitol,2001,31(1):57-62.
[32]Arnot DE,Cavanagh DR,Remarque EJ,et al.Comparative testing of six antigen-based malaria vaccine candidates directed toward merozoite-stage Plasmodium falciparum[J].Clin Vaccine Immunol,2008,15(9):1345-1355.
[33]LI Wengui,CHEN Yatang.Current status of research on vector-mediated MIC vaccine against Toxaplasma gondii[J].Chin J Microecol,2017,29(6):735-738.(in Chinese)李文桂,陈雅棠.载体介导的刚地弓形虫MIC疫苗的研制现状[J].中国微生态学杂志,2017,29(6):735-738.