具有医学危害的有毒动物新型免疫原和毒素疫苗研究进展
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摘要
每年因有毒动物咬伤引发严重临床症状甚至死亡的病例众多。到目前为止,世界公认的最有效的救治药物为抗血清。但传统的抗血清往往通过采用有毒动物成分复杂的全毒免疫马和羊等动物获得,效价受到一定影响;另外,用于患者时不可避免地存在异源过敏和血清病风险。而具有预防作用的毒素疫苗研究相对较少。因此,本文综述了近年来在有毒动物新型免疫原和毒素疫苗方面的研究进展,以期为制备更有效的抗血清和毒素疫苗提供参考。
Every year,many cases of severe clinical symptoms or deaths are caused by venomous animal bites. By the so far,antiserum is considered as the most effective drug. However,traditional antiserum is often prepared by immunization of horse or sheep with crude venom of venomous animals,of which the titer is influenced at a certain degree. In addition,the risks of heterologous allergy and serum diseases are unavoidable for patients. Moreover,there are few studies on prophylactic toxin vaccines. In this paper,we review the advances in study on novel immunogen of venomous animals and toxin vaccines so as to prepare more effective antiserum and toxin vaccines.
Every year,many cases of severe clinical symptoms or deaths are caused by venomous animal bites. By the so far,antiserum is considered as the most effective drug. However,traditional antiserum is often prepared by immunization of horse or sheep with crude venom of venomous animals,of which the titer is influenced at a certain degree. In addition,the risks of heterologous allergy and serum diseases are unavoidable for patients. Moreover,there are few studies on prophylactic toxin vaccines. In this paper,we review the advances in study on novel immunogen of venomous animals and toxin vaccines so as to prepare more effective antiserum and toxin vaccines.
引文
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[2] AKBARI A,RABIEI H,HEDAYAT A,et al. Production of effective antivenin to treat cobra snake(Naja naja oxiana)envenoming[J]. Arch Razi Instit,2010,65(1):33-37.
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[4] ZHANG Z X,ZHENG Y,FAN Q S. Progress in research on snake venom metalloproteinases[J]. Chin J Biologicals,2016,29(7):770-773,777.(in Chinese)张志晓,郑颖,范泉水.蛇毒金属蛋白酶的研究进展[J].中国生物制品学杂志,2016,29(7):770-773,777.
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[9] FELICORI L,FERNANDES P B,GIUSTA M S,et al. An in vivo protective response against toxic effects of the dermonecrotic protein from Loxosceles intermedia spider venom elicited by synthetic epitopes[J]. Vaccine,2009,27(31):4201-4208.
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[11] DE MOURA J,FELICORI L,MOREAU V,et al. Protection against the toxic effects of Loxosceles intermedia spider venom elicited by mimotope peptides[J]. Vaccine,2011,29(45):7992-8001.
[12] MENDES T M,OLIVEIRA D,FIGUEIREDO L F,et al. Generation and characterization of a recombinant chimeric protein(rCpLi)consisting of B-cell epitopes of a dermonecrotic protein from Loxosceles intermedia spider venom[J]. Vaccine,2013,31(25):2749-2755.
[13] DUARTE C G,ALVARENGA L M,DIAS-LOPES C,et al. In vivo protection against Tityus serrulatus scorpion venom by antibodies raised against a discontinuous synthetic epitope[J].Vaccine,2010,28(5):1168-1176.
[14] LILA B A,LARABA-DJEBARI F. Enhanced immune sera and vaccine:safe approach to treat scorpion envenoming[J]. Vaccine,2011,29(48):8951-8959.
[15] ALAM M J,ASHRAF K U M. Prediction of an epitope-based computational vaccine strategy for gaining concurrent immunization against the venom proteins of Australian Box Jellyfish[J]. Toxicol Int,2013,20(3):235-253.
[16] GOIOS A,LUTYNSKA A. Aluminium-adjuvanted vaccines-a review of the current state of knowledge[J]. Przegl Epidemiol,2015,69(4):731-734,871-874.
[17] MASSON J D,THIBAUDON M,BELEC L,et al. Calcium phosphate:a substitute for aluminum adjuvants[J]. Expert Rev Vaccines,2017,16(3):289-299.
[18] OLMEDO H,HERRERA M,ROJAS L,et al. Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom[J]. J Immunotoxicol,2014,11(1):44-49.
[19] HARRISON R A,MOURA-DA-SILVA A M,LAING G D,et al. Antibody from mice immunized with DNA encoding the carboxyl-disintegrin and cysteine-rich domain(JD9)of the haemorrhagic metalloprotease,Jararhagin,inhibits the main lethal component of viper venom[J]. Clin Exp Immunol,2000,121(2):358-363.
[20] MOHAMMADPOURDOUNIGHI N,BEHFAR A,EZABADI A,et al. Preparation of chitosan nanoparticles containing Naja naja oxiana snake venom[J]. Nanomedcine,2010,6(1):137-143.
[21] MOHAMMADPOUR DOUNIGHI N,ESKANDARI R,AVADI M,et al. Preparation and in vitro characterization of chitosan nanoparticles containing Mesobuthus eupeus scorpion venom as an antigen delivery system[J]. J Veno Anim Toxins Including Trop Dis,2012,18(1):44-52.
[22] BUENO-DA-COSTA M H,DE ARAUJO P S,TRINDADE R A.Hoffmeister ion series protected bee venom proteins from damages induced by microencapsulation process[J]. Drug Deliv Lett,2012,2(1):54-59.
[23] ZOLFAGHARIAN H,DOUNIGHI N M. Encapsulation of NajaNaja Oxiana Snake venom into Poly(lactide-co-glycolide)microspheres[J]. Arch Razi Instit,2009,64(2):101-107.
[24] WAGHMARE A,DEOPURKAR R L,SALVI N,et al. Comparison of montanide adjuvants,IMS 3012(nanoparticle),ISA206 and ISA 35(emulsion based)along with incomplete Freund's adjuvant for hyperimmunization of equines used for production of polyvalent snake antivenom[J]. Vaccine,2009,27(7):1067-1072.
[25] WAGHMARE A,SALVI N,DEOPURKAR R L,et al. Evaluation of health status of horses immunized with snake venom and montanide adjuvants,IMS 3012(nanoparticle),ISA 206 and ISA 35(emulsion based)during polyvalent snake antivenom production:Hematological and biochemical assessment[J].Toxicon,2014,82(1):83-92.
[26] SEVERINO M,BONADONNA P,BIL? M,et al. Safety and efficacy of immunotherapy with Polistes dominulus venom:results from a large Italian database[J]. Allergy,2009,64(8):1229-1230.
[27] LEONARD M J,BRESEE C,CRUIKSHANK A. Effects of the canine rattlesnake vaccine in moderate to severe cases of canine crotalid envenomation[J]. Vet Med Res Rep,2014,5:153-158.
[28] CATES C C,VALORE E V,COUTO M A,et al. Comparison of the protective effect of a commercially available western diamondback rattlesnake toxoid vaccine for dogs against envenomation of mice with western diamondback rattlesnake(Crotalus atrox),northern Pacific rattlesnake(Crotalus oreganus oreganus),and southern Pacific rattlesnake(Crotalus oreganus helleri)venom[J]. Am J Vet Res,2015,76(3):272-279.
[29] CHACON F,OVIEDO A,ESCALANTE T,et al. The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom:pathophysiological mechanisms,prophylactic analgesia,and a surrogate in vitro assay[J]. Toxicon,2015,93(1):41-50.
[30] PORNMUTTAKUN D,RATANABANGKOON K. Development of an in vitro potency assay for antivenom against Malayan pit viper(Calloselasma rhodostoma)[J]. Toxicon,2014,77(1):1-5.
[31] OGUIURA N,KAPRONEZAI J,RIBEIRO T,et al. An alternative micromethod to access the procoagulant activity of Bothrops jararaca venom and the efficacy of antivenom[J]. Toxicon,2014,90(1):148-154.
[32] LAINES J,SEGURAA,VILLALTA M,et al. Toxicity of Bothrops sp snake venoms from Ecuador and preclinical assessment of the neutralizing efficacy of a polyspecific antivenom from Costa Rica[J]. Toxicon,2014,88(1):34-37.
[33] GUTIERREZ J M,SOLANO G,PLA D,et al. Assessing the preclinical efficacy of antivenoms:from the lethality neutralization assay to antivenomics[J]. Toxicon,2013,69(1):168-179.
[34] WIESE M D,MILNE R W,DAVIES N W,et al. Myrmecia pilosula(Jack Jumper)ant venom:validation of a procedure to standardise an allergy vaccine[J]. J Pharma Biomed Anal,2008,46(1):58-65.
[2] AKBARI A,RABIEI H,HEDAYAT A,et al. Production of effective antivenin to treat cobra snake(Naja naja oxiana)envenoming[J]. Arch Razi Instit,2010,65(1):33-37.
[3] FRAUCHES T S,PETRETSKI J H,ARNHOLDT A C,et al.Bothropic antivenom based on monoclonal antibodies,is it possible[J]. Toxicon,2013,71(2):49-56.
[4] ZHANG Z X,ZHENG Y,FAN Q S. Progress in research on snake venom metalloproteinases[J]. Chin J Biologicals,2016,29(7):770-773,777.(in Chinese)张志晓,郑颖,范泉水.蛇毒金属蛋白酶的研究进展[J].中国生物制品学杂志,2016,29(7):770-773,777.
[5] AZOFEIFA-CORDERO G,ARCE-ESTRADA V,FLORES-DIAZ M,et al. Immunization with cDNA of a novel P-III type metalloproteinase from the rattlesnake Crotalus durissus durissus elicits antibodies which neutralize 69%of the hemorrhage induced by the whole venom[J]. Toxicon,2008,52(2):302-308.
[6] ARCE-ESTRADA V,AZOFEIFA-CORDERO G,ESTRADA R,et al. Neutralization of venom-induced hemorrhage by equine antibodies raised by immunization with a plasmid encoding a novel P-II metalloproteinase from the lancehead pitviper Bothrops asper[J]. Vaccine,2009,27(3):460-466.
[7] LEAO L I,HO P L JUNQUEIRA-AZEVEDO IDE L. Transcriptomic basis for an antiserum against Micrurus corallinus(coral snake)venom[J]. BMC Genomics,2009,10:112. doi:10.1186/1471-2164-10-112.
[8] RAMOS H R,HO P L. Developing snake antivenom sera by genetic immunization:a review[M]. Springer:Clinical Toxinology,2014:1-12.
[9] FELICORI L,FERNANDES P B,GIUSTA M S,et al. An in vivo protective response against toxic effects of the dermonecrotic protein from Loxosceles intermedia spider venom elicited by synthetic epitopes[J]. Vaccine,2009,27(31):4201-4208.
[10] DIAS-LOPES C,GUIMARAES G,FELICORI L,et al. A protective immune response against lethal, dermonecrotic and hemorrhagic effects of Loxosceles intermedia venom elicited by a 27-residue peptide[J]. Toxicon,2010,55(2-3):481-487.
[11] DE MOURA J,FELICORI L,MOREAU V,et al. Protection against the toxic effects of Loxosceles intermedia spider venom elicited by mimotope peptides[J]. Vaccine,2011,29(45):7992-8001.
[12] MENDES T M,OLIVEIRA D,FIGUEIREDO L F,et al. Generation and characterization of a recombinant chimeric protein(rCpLi)consisting of B-cell epitopes of a dermonecrotic protein from Loxosceles intermedia spider venom[J]. Vaccine,2013,31(25):2749-2755.
[13] DUARTE C G,ALVARENGA L M,DIAS-LOPES C,et al. In vivo protection against Tityus serrulatus scorpion venom by antibodies raised against a discontinuous synthetic epitope[J].Vaccine,2010,28(5):1168-1176.
[14] LILA B A,LARABA-DJEBARI F. Enhanced immune sera and vaccine:safe approach to treat scorpion envenoming[J]. Vaccine,2011,29(48):8951-8959.
[15] ALAM M J,ASHRAF K U M. Prediction of an epitope-based computational vaccine strategy for gaining concurrent immunization against the venom proteins of Australian Box Jellyfish[J]. Toxicol Int,2013,20(3):235-253.
[16] GOIOS A,LUTYNSKA A. Aluminium-adjuvanted vaccines-a review of the current state of knowledge[J]. Przegl Epidemiol,2015,69(4):731-734,871-874.
[17] MASSON J D,THIBAUDON M,BELEC L,et al. Calcium phosphate:a substitute for aluminum adjuvants[J]. Expert Rev Vaccines,2017,16(3):289-299.
[18] OLMEDO H,HERRERA M,ROJAS L,et al. Comparison of the adjuvant activity of aluminum hydroxide and calcium phosphate on the antibody response towards Bothrops asper snake venom[J]. J Immunotoxicol,2014,11(1):44-49.
[19] HARRISON R A,MOURA-DA-SILVA A M,LAING G D,et al. Antibody from mice immunized with DNA encoding the carboxyl-disintegrin and cysteine-rich domain(JD9)of the haemorrhagic metalloprotease,Jararhagin,inhibits the main lethal component of viper venom[J]. Clin Exp Immunol,2000,121(2):358-363.
[20] MOHAMMADPOURDOUNIGHI N,BEHFAR A,EZABADI A,et al. Preparation of chitosan nanoparticles containing Naja naja oxiana snake venom[J]. Nanomedcine,2010,6(1):137-143.
[21] MOHAMMADPOUR DOUNIGHI N,ESKANDARI R,AVADI M,et al. Preparation and in vitro characterization of chitosan nanoparticles containing Mesobuthus eupeus scorpion venom as an antigen delivery system[J]. J Veno Anim Toxins Including Trop Dis,2012,18(1):44-52.
[22] BUENO-DA-COSTA M H,DE ARAUJO P S,TRINDADE R A.Hoffmeister ion series protected bee venom proteins from damages induced by microencapsulation process[J]. Drug Deliv Lett,2012,2(1):54-59.
[23] ZOLFAGHARIAN H,DOUNIGHI N M. Encapsulation of NajaNaja Oxiana Snake venom into Poly(lactide-co-glycolide)microspheres[J]. Arch Razi Instit,2009,64(2):101-107.
[24] WAGHMARE A,DEOPURKAR R L,SALVI N,et al. Comparison of montanide adjuvants,IMS 3012(nanoparticle),ISA206 and ISA 35(emulsion based)along with incomplete Freund's adjuvant for hyperimmunization of equines used for production of polyvalent snake antivenom[J]. Vaccine,2009,27(7):1067-1072.
[25] WAGHMARE A,SALVI N,DEOPURKAR R L,et al. Evaluation of health status of horses immunized with snake venom and montanide adjuvants,IMS 3012(nanoparticle),ISA 206 and ISA 35(emulsion based)during polyvalent snake antivenom production:Hematological and biochemical assessment[J].Toxicon,2014,82(1):83-92.
[26] SEVERINO M,BONADONNA P,BIL? M,et al. Safety and efficacy of immunotherapy with Polistes dominulus venom:results from a large Italian database[J]. Allergy,2009,64(8):1229-1230.
[27] LEONARD M J,BRESEE C,CRUIKSHANK A. Effects of the canine rattlesnake vaccine in moderate to severe cases of canine crotalid envenomation[J]. Vet Med Res Rep,2014,5:153-158.
[28] CATES C C,VALORE E V,COUTO M A,et al. Comparison of the protective effect of a commercially available western diamondback rattlesnake toxoid vaccine for dogs against envenomation of mice with western diamondback rattlesnake(Crotalus atrox),northern Pacific rattlesnake(Crotalus oreganus oreganus),and southern Pacific rattlesnake(Crotalus oreganus helleri)venom[J]. Am J Vet Res,2015,76(3):272-279.
[29] CHACON F,OVIEDO A,ESCALANTE T,et al. The lethality test used for estimating the potency of antivenoms against Bothrops asper snake venom:pathophysiological mechanisms,prophylactic analgesia,and a surrogate in vitro assay[J]. Toxicon,2015,93(1):41-50.
[30] PORNMUTTAKUN D,RATANABANGKOON K. Development of an in vitro potency assay for antivenom against Malayan pit viper(Calloselasma rhodostoma)[J]. Toxicon,2014,77(1):1-5.
[31] OGUIURA N,KAPRONEZAI J,RIBEIRO T,et al. An alternative micromethod to access the procoagulant activity of Bothrops jararaca venom and the efficacy of antivenom[J]. Toxicon,2014,90(1):148-154.
[32] LAINES J,SEGURAA,VILLALTA M,et al. Toxicity of Bothrops sp snake venoms from Ecuador and preclinical assessment of the neutralizing efficacy of a polyspecific antivenom from Costa Rica[J]. Toxicon,2014,88(1):34-37.
[33] GUTIERREZ J M,SOLANO G,PLA D,et al. Assessing the preclinical efficacy of antivenoms:from the lethality neutralization assay to antivenomics[J]. Toxicon,2013,69(1):168-179.
[34] WIESE M D,MILNE R W,DAVIES N W,et al. Myrmecia pilosula(Jack Jumper)ant venom:validation of a procedure to standardise an allergy vaccine[J]. J Pharma Biomed Anal,2008,46(1):58-65.