Immunoprofiling of Equine Plasma against Deinagkistrodon acutus in Taiwan: Key to Understanding Differential Neutralization Potency in Immunized Horses.
Abstract: Snakebite envenoming is a public health issue linked to high mortality and morbidity rates worldwide. Although antivenom has been the mainstay treatment for envenomed victims receiving medical care, the diverse therapeutic efficacy of the produced antivenom is a major limitation. is a venomous snake that poses significant concern of risks to human life in Taiwan, and successful production of antivenom against envenoming remains a considerable challenge. Among groups of horses subjected to immunization schedules, few or none subsequently meet the quality required for further scale-up harvesting. The determinants underlying the variable immune responses of horses to venom are currently unknown. In this study, we assessed the immunoprofiles of high-potency and low-potency horse plasma against venom and explored the conspicuous differences between these two groups. Based on the results of liquid chromatography with tandem mass spectrometry (LC-MS/MS), acutolysin A was identified as the major component of venom proteins that immunoreacted differentially with the two plasma samples. Our findings indicate underlying differences in antivenoms with variable neutralization efficacies, and may provide valuable insights for improvement of antivenom production in the future.
Publication Date: 2023-01-09 PubMed ID: 36668958PubMed Central: PMC9866385DOI: 10.3390/tropicalmed8010051Google Scholar: Lookup
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- Journal Article
Summary
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The research involves analysis of the different immune responses in horses against the venom of the Deinagkistrodon acutus snake in Taiwan. The aim is to improve the quality and effectiveness of antivenom produced for treating snakebite envenoming, which results in significantly high mortality and morbidity rates worldwide.
Introduction and Background
- Snakebite envenoming is identified as a significant public health issue across the globe, associated with high rates of mortality and morbidity. Therefore, the development of effective antivenom treatments is crucial.
- The study focuses on venom from Deinagkistrodon acutus, a snake species in Taiwan that poses a significant threat to human lives. It’s noted that producing a successful antivenom against this snake’s venom remains a significant challenge.
- Researchers have noted that only a small number or none of the immunized horses meet the required quality for large-scale harvesting (production) of antivenom. Hence, there is a need for robust research to understand the determinants of variable immune responses in these horses.
Aim and Methodology
- The researchers aim to assess the immunoprofiles of horse plasma with different potency levels (high and low) against the venom of Deinagkistrodon acutus.
- A key objective is to explore noticeable distinctions between these two potency groups. The research will aid in understanding different immune reactions and improve the efficacy of antivenom.
- They use liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify the primary venom protein that reacts differentially to the two plasma samples.
Findings and Conclusions
- Researchers identified acutolysin A as the venom’s main protein component, which showed an apparent differential immunoreaction in the plasma samples.
- This finding highlights underlying differences in antivenoms and contributes to an understanding of the variations in neutralization efficacies.
- The study concludes that such findings could provide essential insights for enhancing antivenom production in the future. Improving the quality and quantity of antivenom produced will aid in effectively treating victims subjected to snakebite envenoming.
Cite This Article
APA
Wu CJ, Liaw GW, Chen CK, Ouyang CH, Yang YX, Chu LC, Hsiao YC, Liu CH, Hsieh WC, Wang CY, Liou YS, Liu CC, Hsieh CH.
(2023).
Immunoprofiling of Equine Plasma against Deinagkistrodon acutus in Taiwan: Key to Understanding Differential Neutralization Potency in Immunized Horses.
Trop Med Infect Dis, 8(1), 51.
https://doi.org/10.3390/tropicalmed8010051 Publication
Researcher Affiliations
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
- Department of Emergency Medicine, Yeezen General Hospital, Taoyuan 32645, Taiwan.
- Master Program of Health Policy and Business Administration, College of Technology Management, National Tsing Hua University, Hsinchu 30013, Taiwan.
- Department of Emergency Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
- Department of Trauma and Emergency Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
- College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
- Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
- Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
- Department of Otolaryngology Head and Neck Surgery, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan.
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
- Center for Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei 11561, Taiwan.
- Center for Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei 11561, Taiwan.
- Center for Diagnostics and Vaccine Development, Centers for Disease Control, Ministry of Health and Welfare, Taipei 11561, Taiwan.
- Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
- Molecular Medicine Research Center, Chang Gung University, Taoyuan 33302, Taiwan.
- Department of Emergency Medicine, En Chu Kong Hospital, New Taipei City 23741, Taiwan.
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan.
Grant Funding
- 110-2314-B-182A-012 / Ministry of Science and Technology, Taiwan
- ECKH_W11003 / En Chu Kong Hospital, Taiwan
- ECKH_W11106 / En Chu Kong Hospital, Taiwan
- CMRPG3M0241 / Chang Gung Memorial Hospital, Taiwan
- CMRPG3L1231 / Chang Gung Memorial Hospital, Taiwan
Conflict of Interest Statement
The authors declare no conflict of interest.
References
This article includes 51 references
- Chippaux JP. Snake-bites: appraisal of the global situation.. Bull World Health Organ 1998;76(5):515-24.
- Kasturiratne A, Wickremasinghe AR, de Silva N, Gunawardena NK, Pathmeswaran A, Premaratna R, Savioli L, Lalloo DG, de Silva HJ. The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths.. PLoS Med 2008 Nov 4;5(11):e218.
- Gutiérrez JM, Calvete JJ, Habib AG, Harrison RA, Williams DJ, Warrell DA. Snakebite envenoming.. Nat Rev Dis Primers 2017 Oct 5;3:17079.
- Chang KP, Lai CS, Lin SD. Management of poisonous snake bites in southern Taiwan.. Kaohsiung J Med Sci 2007 Oct;23(10):511-8.
- Su HY, Huang SW, Mao YC, Liu MW, Lee KH, Lai PF, Tsai MJ. Clinical and laboratory features distinguishing between Deinagkistrodon acutus and Daboia siamensis envenomation.. J Venom Anim Toxins Incl Trop Dis 2018;24:43.
- Huang J, Zhao M, Xue C, Liang J, Huang F. Analysis of the Composition of Deinagkistrodon acutus Snake Venom Based on Proteomics, and Its Antithrombotic Activity and Toxicity Studies.. Molecules 2022 Mar 29;27(7).
- Chen PC, Huang MN, Chang JF, Liu CC, Chen CK, Hsieh CH. Snake venom proteome and immuno-profiling of the hundred-pace viper, Deinagkistrodon acutus, in Taiwan.. Acta Trop 2019 Jan;189:137-144.
- Tan KY, Shamsuddin NN, Tan CH. Sharp-nosed Pit Viper (Deinagkistrodon acutus) from Taiwan and China: A comparative study on venom toxicity and neutralization by two specific antivenoms across the Strait.. Acta Trop 2022 Aug;232:106495.
- Meyer WP, Habib AG, Onayade AA, Yakubu A, Smith DC, Nasidi A, Daudu IJ, Warrell DA, Theakston RD. First clinical experiences with a new ovine Fab Echis ocellatus snake bite antivenom in Nigeria: randomized comparative trial with Institute Pasteur Serum (Ipser) Africa antivenom.. Am J Trop Med Hyg 1997 Mar;56(3):291-300.
- Bochner R. Paths to the discovery of antivenom serotherapy in France.. J Venom Anim Toxins Incl Trop Dis 2016;22:20.
- Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States.. Ann Emerg Med 2001 Feb;37(2):181-8.
- de Silva HA, Ryan NM, de Silva HJ. Adverse reactions to snake antivenom, and their prevention and treatment.. Br J Clin Pharmacol 2016 Mar;81(3):446-52.
- Meenatchisundaram S, Parameswari G, Michael A, Ramalingam S. Studies on pharmacological effects of Russell's viper and Saw-scaled viper venom and its neutralization by chicken egg yolk antibodies.. Int Immunopharmacol 2008 Aug;8(8):1067-73.
- Karlson-Stiber C, Persson H. Antivenom treatment in Vipera berus envenoming--report of 30 cases.. J Intern Med 1994 Jan;235(1):57-61.
- León G, Herrera M, Segura Á, Villalta M, Vargas M, Gutiérrez JM. Pathogenic mechanisms underlying adverse reactions induced by intravenous administration of snake antivenoms.. Toxicon 2013 Dec 15;76:63-76.
- . Progress in the characterization of venoms and standardization of antivenoms.. WHO Offset Publ 1981;(58):1-44.
- Harrison RA, Hargreaves A, Wagstaff SC, Faragher B, Lalloo DG. Snake envenoming: a disease of poverty.. PLoS Negl Trop Dis 2009 Dec 22;3(12):e569.
- Brown NI. Consequences of neglect: analysis of the sub-Saharan African snake antivenom market and the global context.. PLoS Negl Trop Dis 2012;6(6):e1670.
- Habib AG, Lamorde M, Dalhat MM, Habib ZG, Kuznik A. Cost-effectiveness of antivenoms for snakebite envenoming in Nigeria.. PLoS Negl Trop Dis 2015 Jan;9(1):e3381.
- Harrison RA, Cook DA, Renjifo C, Casewell NR, Currier RB, Wagstaff SC. Research strategies to improve snakebite treatment: challenges and progress.. J Proteomics 2011 Aug 24;74(9):1768-80.
- Chippaux JP. The development and use of immunotherapy in Africa.. Toxicon 1998 Nov;36(11):1503-6.
- Patikorn C, Ismail AK, Abidin SAZ, Blanco FB, Blessmann J, Choumlivong K, Comandante JD, Doan UV, Mohamed Ismail Z, Khine YY, Maharani T, Nwe MT, Qamruddin RM, Safferi RS, Santamaria E, Tiglao PJG, Trakulsrichai S, Vasaruchapong T, Chaiyakunapruk N, Taychakhoonavudh S, Othman I. Situation of snakebite, antivenom market and access to antivenoms in ASEAN countries.. BMJ Glob Health 2022 Mar;7(3).
- Alangode A, Rajan K, Nair BG. Snake antivenom: Challenges and alternate approaches.. Biochem Pharmacol 2020 Nov;181:114135.
- Isbister GK. Antivenom efficacy or effectiveness: the Australian experience.. Toxicology 2010 Feb 9;268(3):148-54.
- Maria WS, Cambuy MO, Costa JO, Velarde DT, Chávez-Olórtegui C. Neutralizing potency of horse antibothropic antivenom. Correlation between in vivo and in vitro methods.. Toxicon 1998 Oct;36(10):1433-9.
- Santos Barreto GN, de Oliveira SS, Dos Anjos IV, Chalkidis HM, Mourão RH, Moura-da-Silva AM, Sano-Martins IS, Gonçalves LR. Experimental Bothrops atrox envenomation: Efficacy of antivenom therapy and the combination of Bothrops antivenom with dexamethasone.. PLoS Negl Trop Dis 2017 Mar;11(3):e0005458.
- Muniz EG, Maria WS, Estevão-Costa MI, Buhrnheim P, Chávez-Olórtegui C. Neutralizing potency of horse antibothropic Brazilian antivenom against Bothrops snake venoms from the Amazonian rain forest.. Toxicon 2000 Dec;38(12):1859-63.
- Oshima-Franco Y, Hyslop S, Prado-Franceschi J, Cruz-Höfling MA, Rodrigues-Simioni L. Neutralizing capacity of antisera raised in horses and rabbits against Crotalus durissus terrificus (South American rattlesnake) venom and its main toxin, crotoxin.. Toxicon 1999 Oct;37(10):1341-57.
- Villalta M, Pla D, Yang SL, Sanz L, Segura A, Vargas M, Chen PY, Herrera M, Estrada R, Cheng YF, Lee CD, Cerdas M, Chiang JR, Angulo Y, León G, Calvete JJ, Gutiérrez JM. Snake venomics and antivenomics of Protobothrops mucrosquamatus and Viridovipera stejnegeri from Taiwan: keys to understand the variable immune response in horses.. J Proteomics 2012 Oct 22;75(18):5628-45.
- KUWAJIMA Y. Immunological researches on the main Formosan poisonous snakes, especially on the venoms. 5. Therapeutic experiment of mice injected with the snake venom by means of the antivenin serum.. Jpn J Exp Med 1953 Oct;23(5):457-64.
- Liau MY, Huang RJ. Toxoids and antivenoms of venomous snakes in Taiwan. J. Toxicol. Toxin. Rev. 1997;16:163–175.
- Howard-Jones N. A CIOMS ethical code for animal experimentation.. WHO Chron 1985;39(2):51-6.
- Liu CC, Hsiao YC, Chu LJ, Wang PJ, Liu CH, Hsieh WC, Yu JS. Development of Antibody Detection ELISA Based on Immunoreactive Toxins and Toxin-Derived Peptides to Evaluate the Neutralization Potency of Equine Plasma against Naja atra in Taiwan.. Toxins (Basel) 2021 Nov 19;13(11).
- Liu CC, Wu CJ, Hsiao YC, Yang YH, Liu KL, Huang GJ, Hsieh CH, Chen CK, Liaw GW. Snake venom proteome of Protobothrops mucrosquamatus in Taiwan: Delaying venom-induced lethality in a rodent model by inhibition of phospholipase A(2) activity with varespladib.. J Proteomics 2021 Mar 15;234:104084.
- Liu CC, Lin CC, Hsiao YC, Wang PJ, Yu JS. Proteomic characterization of six Taiwanese snake venoms: Identification of species-specific proteins and development of a SISCAPA-MRM assay for cobra venom factors.. J Proteomics 2018 Sep 15;187:59-68.
- Liu Q, Xu W, Cheng X, Jin G, Shen X, Lou H, Liu J. Molecular cloning and sequence analysis of cDNA encoding haemorrhagic toxin acutolysin A from Agkistrodon acutus.. Toxicon 1999 Nov;37(11):1539-48.
- Bode W, Gomis-Rüth FX, Stöckler W. Astacins, serralysins, snake venom and matrix metalloproteinases exhibit identical zinc-binding environments (HEXXHXXGXXH and Met-turn) and topologies and should be grouped into a common family, the 'metzincins'.. FEBS Lett 1993 Sep 27;331(1-2):134-40.
- Borkakoti N, Winkler FK, Williams DH, D'Arcy A, Broadhurst MJ, Brown PA, Johnson WH, Murray EJ. Structure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor.. Nat Struct Biol 1994 Feb;1(2):106-10.
- Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N, Martinez-Fierro ML. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases.. Int J Mol Sci 2020 Dec 20;21(24).
- Gutiérrez JM, Escalante T, Rucavado A, Herrera C. Hemorrhage Caused by Snake Venom Metalloproteinases: A Journey of Discovery and Understanding.. Toxins (Basel) 2016 Mar 26;8(4):93.
- Xu X, Wang C, Liu J, Lu Z. Purification and characterization of hemorrhagic components from Agkistrodon acutus (hundred pace snake) venom.. Toxicon 1981;19(5):633-44.
- Cheng CL, Mao YC, Liu PY, Chiang LC, Liao SC, Yang CC. Deinagkistrodon acutus envenomation: a report of three cases.. J Venom Anim Toxins Incl Trop Dis 2017;23:20.
- Valenta J, Stach Z, Michálek P. Envenoming by Crotalid Snake Chinese Moccasin Agkistrodon Acutus Bite - A Case Report.. Prague Med Rep 2015;116(2):155-60.
- Huang F, Zhao S, Tong F, Liang Y, Le Grange JM, Kuang W, Zhou Y. Unexpected death in a young man associated with a unilateral swollen leg: Pathological and toxicological findings in a fatal snakebite from Deinagkistrodon acutus (Chinese moccasin).. J Forensic Sci 2021 Mar;66(2):786-792.
- Li QB, Yu QS, Huang GW, Tokeshi Y, Nakamura M, Kinjoh K, Kosugi T. Hemostatic disturbances observed in patients with snakebite in south China.. Toxicon 2000 Oct;38(10):1355-66.
- Williams DJ, Gutiérrez JM, Calvete JJ, Wüster W, Ratanabanangkoon K, Paiva O, Brown NI, Casewell NR, Harrison RA, Rowley PD, O'Shea M, Jensen SD, Winkel KD, Warrell DA. Ending the drought: new strategies for improving the flow of affordable, effective antivenoms in Asia and Africa.. J Proteomics 2011 Aug 24;74(9):1735-67.
- Laustsen AH, Karatt-Vellatt A, Masters EW, Arias AS, Pus U, Knudsen C, Oscoz S, Slavny P, Griffiths DT, Luther AM, Leah RA, Lindholm M, Lomonte B, Gutiérrez JM, McCafferty J. In vivo neutralization of dendrotoxin-mediated neurotoxicity of black mamba venom by oligoclonal human IgG antibodies.. Nat Commun 2018 Oct 2;9(1):3928.
- Ahmad ZA, Yeap SK, Ali AM, Ho WY, Alitheen NB, Hamid M. scFv antibody: principles and clinical application.. Clin Dev Immunol 2012;2012:980250.
- Bulfone TC, Samuel SP, Bickler PE, Lewin MR. Developing Small Molecule Therapeutics for the Initial and Adjunctive Treatment of Snakebite.. J Trop Med 2018;2018:4320175.
- Gutiérrez JM, Rucavado A, Ovadia M. Metalloproteinase inhibitors in snakebite envenomations.. Drug Discov Today 1999 Nov;4(11):532-533.
- Albulescu LO, Xie C, Ainsworth S, Alsolaiss J, Crittenden E, Dawson CA, Softley R, Bartlett KE, Harrison RA, Kool J, Casewell NR. A therapeutic combination of two small molecule toxin inhibitors provides broad preclinical efficacy against viper snakebite.. Nat Commun 2020 Dec 15;11(1):6094.
Citations
This article has been cited 2 times.- Liu CC, Chou YS, Yang YX, Hsiao YC, Chu LJ, Yang C, Yan Z, Peng R, Chao HY, Li MX, Wu CJ. Enhancing Deinagkistrodon acutus antivenom potency through acutolysin A-targeted antibody supplementation. PLoS Negl Trop Dis 2025 Dec;19(12):e0013847.
- Zhu H, Pan Y, Tai Z, Wang M, Liu X, Yu X, He Q. Epitope-based antibody development against metalloproteinases and phospholipases A(2) from Deinagkistrodon acutus venom. J Venom Anim Toxins Incl Trop Dis 2025;31:e20240060.
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