Prospects of Obtaining Antitoxins and Immunoglobulin Preparations from Animal Blood, Their Purification and Application

Authors

DOI:

https://doi.org/10.60988/p.v36i3.37

Keywords:

antitoxin, immunoglobulin preparation, F(ab’)2 fragments, antivenom, proteolytic digestion

Abstract

Animal hyperimmune sera containing specific protective antibodies against bacterial and viral antigens, snake and insect venoms have been used for more than 120 years. Currently, antitoxins against bacterial toxins (diphtheria, tetanus, botulism, etc.), viruses (rabies, Ebola, SARS-CoV-2, etc.), venoms of snakes (viper, gyurza, efa, cobra, etc.), spiders (black widow spider, red-backed spider, etc.), and scorpions have been developed and are successfully used.  The review is devoted to modern technologies for producing antitoxins and immunoglobulin preparations, as well as the main areas of their application, such as the prevention or treatment of bacterial and viral diseases, bites of venomous snakes and spiders. The main stages of the production of antitoxins and immunoglobulin preparations are considered. An important step in the production of these drugs is the proteolytic digestion of native immunoglobulin molecules using enzymes to obtain F(ab')2-fragments and remove Fc-fragments, that leads to the elimination of undesirable interactions with Fc-receptors in tissue, which reduces the frequency of side effects. Today, antitoxins and immunoglobulin preparations are widely used in practical medicine. In addition to the application of well-known antitoxins, purification methods are being improved and new drugs are being developed to fight with actual threats such as antitoxin against COVID-19.

References

Popoff M.R., Faure G., Legout S., Ladant D. Animal Toxins: A Historical Outlook at the Institut Pasteur of Paris. Toxins. 15, 462, 2023. https://doi.org/10.3390/toxins15070462

Cholakov I. (1987). Nobel Prizes. Scientists and discoveries. Moscow, World, pp. 369.

Krasnopolsky Yu.M., Borshchevskaya M.I. (2008). Biotechnology of immunobiological preparations. Kharkiv, Farmitek, pp. 267-288.

Ek N. Serum levels of the immunoglobulins IgG and IgG(T) in horses. Acta veterinaria Scandinavica. 15, 609-619, 1974. https://doi.org/10.1186/BF03547230

Wagner B. Immunoglobulins and immunoglobulin genes of the horse. Developmental and comparative immunology. 30, 155-164, 2006. https://doi.org/10.1016/j.dci.2005.06.008

Burgasova P.N.(ed). (1978) Guide to vaccine-serum production. Moscow, Medicine, pp. 439.

Karpov S.P., Prager S.M., Sinelnikov G.E., Fedorov Yu.V. (1976). Hyperimmune serums. Tomsk, Publishing house TSU, pp. 376.

Korshun S.V., Nedrigailov V.I., Ostryanin G.Ya. (1902). On obtaining anti-diphtheria serum rich in antitoxins. In: Materials of reports at the Pirogov Congress. Moscow.

Golbets I.I. (1998). To the 100th anniversary of the Biolek enterprise. Scientific research. In: Collection of reports of the scientific and practical conference “Standardization, control and production of immunobiological and medicinal products”, dedicated to the 100th anniversary of the Kharkov enterprise “Biolek”». Kharkiv, pp. 12-35.

Petrenko M.D., Cherkas G.P., Ponomarenko M.G. Obtaining polyvalent serums against gas gangrene and tetanus. Collection of works of the Kharkov Mechnikov Research Institute of Vaccines and Serums. 27, 141-144. 1963.

Golbets I.I., Kazarova T.A., Orlova G.L.. Dynamics of biochemical and immunochemical properties of purified toxoid Cl. oedematiens in the process of its manufacture. Vaccines and Serums. 7, 66-78, 1973.

Golbets I.I. On the issue of fractionation of botulinum antigens types A and B. Theoretical and practical issues of vaccine-serum business : Republican interdepartmental collection. 3, 89-100, 1969.

Dalin M.V., Fish N.G. (1980). Protein toxins of microbes. Moscow, Medicine, pp. 224.

Sonobe M.H., A Trezena.G., Guilhen F.B., Takano V.L., Fratelli F., Sakauchi D., Morais J.F., Prado S.M., Higashi H.G. Determination of low tetanus or diphtheria antitoxin titers in sera by a toxin neutralization assay and a modified toxin-binding inhibition test. Brazilian journal of medical and biological research. 40, 69-76, 2007. https://doi.org/10.1590/s0100-879x2007000100009

Smith H.L., Saia G., Lobikin M., T. Tiwari, S.C. Cheng, D.C. Molrine. Characterization of serum anti-diphtheria antibody activity following administration of equine anti-toxin for suspected diphtheria. Human vaccines & immunotherapeutics. 13, 2738-2741, 2017. https://doi.org/10.1080/21645515.2017.1362516

Bermejo-Martin J.F., Avila-Alonso A., González-Rivera M., Tamayo E., Eiros J.M., Almansa R. Postbooster Antibodies from Humans as Source of Diphtheria Antitoxin. Emerging infectious diseases. 22, 1265-1267, 2016. https://doi.org/10.3201/eid2207.151670

Mezin I.A., Menzeleev R.F., Krasnopolsky Yu.M.. Purification of tetanus toxin by affinity chromatography on reversed-phase sorbents with adsorbed gangliosides. Biotechnology. 4, 22-25, 1992.

Calvo A.C., Oliván S., Manzano R., Zaragoza P., Aguilera J., Osta R. Fragment C of tetanus toxin: new insights into its neuronal signaling pathway. International journal of molecular sciences. 13, 6883-6901, 2012. https://doi.org/10.3390/ijms13066883

Yu R., Ji C., Xu J., Wang D., Fang T., Jing Y., Kwang-Fu Shen C., Chen W. The Immunogenicity of the C Fragment of Tetanus Neurotoxin in Production of Tetanus Antitoxin. BioMed research international. 2018, 6057348, 2018. https://doi.org/10.1155/2018/6057348

Helting T.B., Zwisler O.. Structure of tetanus toxin. I. Breakdown of the toxin molecule and discrimination between polypeptide fragments. The Journal of biological chemistry 252, 187-193, 1977.

Joseph M., Woldeamanuel Y., Medhin G., Manyazewal T., Fekadu A., Makonnen E.. Safety of equine tetanus antitoxin for prophylactic use in Ethiopia: a retrospective multi-center study. Tropical medicine and health. 51, 23, 2023. https://doi.org/10.1186/s41182-023-00518-8

Giri B., Kole L. (2015). Combating the Insidious Enemy: Epidemiology, Pathophysiology, and Treatment of Clostridial Gas Gangrene. In: Gopalakrishnakone P., Balali-Mood M., Llewellyn L., Singh B.R. Ed(s). Biological Toxins and Bioterrorism. Toxinology. Dordrecht, Springer, pp. 425–448. https://doi.org/10.1007/978-94-007-5869-8_36

Fu Y., Alenezi T., Sun X. Clostridium perfringens-Induced Necrotic Diseases: An Overview. Immuno. 2, 387-407, 2022. https://doi.org/10.3390/immuno2020024

Aggelidakis J., Lasithiotakis K., Topalidou A., Koutroumpas J., Kouvidis G., Katonis P..Limb salvage after gas gangrene: a case report and review of the literature. World journal of emergency surgery : WJES. 6, 28, 2011. https://doi.org/10.1186/1749-7922-6-28

Becker M. On the production of gas gangrene serum in general and of polyvalent gas gangrene aphylacto-serum of the horse especially using the simultaneous immunization method with the 4 known gas gangrene types in uno. Archiv fur experimentelle Veterinarmedizin. 21, 519-546, 1967.

Yanamoto A., Ito A., Murata R., Uematsu N., Nagai K. Hyperimmunization of horses with alpha toxoid of Clostridium perfringens. Japanese journal of medical science & biology. 23, 111-115, 1970. https://doi.org/10.7883/yoken1952.23.111

Orlova G.L., Krasnopolsky Yu.M., Golbets I.I. (1981). Standardization of methods for monitoring and specific activity of gangrenous toxins and anti-gangrenous serums. In: Current issues of immunoprophylaxis of viral and bacterial infections, Tomsk. pp. 179-180.

Chai T., Liu X., Wang H., inventors; Shandong Agricultural University, assignee. C and D type C. perfringens antitoxin serum and preparation method thereof. China patent 104829712A. 2015.

Komarovskaya E.I., Perelygina O.V. Current incidence of certain clostridial infections: gas gangrene and tetanus. Biopreparations. Biogical Products Prevention, Diagnostis, Treatment. 21, 31-38, 2021. http://dx.doi.org/10.30895/2221-996X-2021-21-1-31-38

Hifumi T., Koido Y., Takahashi M., Yamamoto A. Antitoxin treatment for liver abscess caused by Clostridium perfringens. Clinical and molecular hepatology. 19, 97-98, 2013. https://doi.org/10.3350/cmh.2013.19.1.97

Liu S., Yang X., Zhang H., Zhang J., Zhou Y., Wang T., Hu N., Deng X., Bai X., Wang J. Amentoflavone Attenuates Clostridium perfringens Gas Gangrene by Targeting Alpha-Toxin and Perfringolysin O. Frontiers in pharmacology. 11, 179, 2020. https://doi.org/10.3389/fphar.2020.00179

Zhang J., Liu S., Xia L., Wen Z., Hu N., Wang T., Deng X., He J., Wang J. Verbascoside Protects Mice From Clostridial Gas Gangrene by Inhibiting the Activity of Alpha Toxin and Perfringolysin O. Frontiers in microbiology. 11, 1504, 2020. https://doi.org/10.3389/fmicb.2020.01504

Wendt S., Eder I., Wölfel R., Braun P., Lippmann N., Rodloff A. Botulism: Diagnosis and Therapy. Deutsche medizinische Wochenschrift. 142, 1304-1312, 2017. https://doi.org/10.1055/s-0043-112232

Silvaggi N.R., Boldt G.E., Hixon M.S., Kennedy J.P., Tzipori S., Janda K.D., Allen K.N. Structures of Clostridium botulinum Neurotoxin Serotype A Light Chain complexed with small-molecule inhibitors highlight active-site flexibility. Chemistry & biology. 14, 533-542, 2007. https://doi.org/10.1016/j.chembiol.2007.03.014

Matak I., Lacković Z. Botulinum neurotoxin type A: Actions beyond SNAP-25. Toxicology. 335, 79-84, 2015. https://doi.org/10.1016/j.tox.2015.07.003

Siegel L.S. Evaluation of neutralizing antibodies to type A, B, E, and F botulinum toxins in sera from human recipients of botulinum pentavalent (ABCDE) toxoid. Journal of clinical microbiology. 27, 1906-1908, 1989. https://doi.org/10.1128/jcm.27.8.1906-1908.1989

Li D., Mattoo P., Keller J.E.. New equine antitoxins to botulinum neurotoxins serotypes A and B. Biologicals : journal of the International Association of Biological Standardization. 40, 240-246, 2012. https://doi.org/10.1016/j.biologicals.2012.03.004

Kim N.Y., Park K.E., Lee Y.J., Kim Y.M., Hong S.H., Son W.R., Hong S., Lee S., Ahn H.B., Yang J., Seo J.P., Lim Y.K., Yu C.H., Hur G.H., Jeong S.T., Lee H.S., Song K., Kang T.J., Shin Y.K., Choi J.S., Choi J.Y. Development of an Equine Antitoxin by Immunizing the Halla Horse with the Receptor-Binding Domain of Botulinum Neurotoxin Type A1. Journal of microbiology and biotechnology. 29, 1165-1176, 2019. https://doi.org/10.4014/jmb.1904.04027

Shi D.Y., Lu J.S., Mao Y.Y., Liu F.J., Wang R., Du P., Yu S., Yu Y.Z., Yang Z.X. Characterization of a novel tetravalent botulism antitoxin based on receptor-binding domain of BoNTs. Biotechnological Products and Process Engineering. 107, 3205–32162023. https://doi.org/10.1007/s00253-023-12515-2

Shi D.Y., Liu F.J., Mao Y.Y., Cui R.T., Lu J.S., Yu Y.Z., Dong X.J., Yang Z.X., Sun Z.W., Pang X.B. Development and evaluation of candidate subunit vaccine and novel antitoxin against botulinum neurotoxin serotype E. Human vaccines & immunotherapeutics. 16, 100-108, 2020. https://doi.org/10.1080/21645515.2019.1633878

Rasetti-Escargueil C., Popoff M.R. Antibodies and Vaccines against Botulinum Toxins: Available Measures and Novel Approaches. Toxins. 11, 528, 2019. https://doi.org/10.3390/toxins11090528

Wheeler M.W. Production of Monovalent Botulinus Antitoxic Serum Types A and B. The Journal of immunology. 8, 501–505, 1923. https://doi.org/10.4049/jimmunol.8.6.501

Rao A.K., Sobel J., Chatham-Stephens K., Luquez C. Clinical Guidelines for Diagnosis and Treatment of Botulism, 2021. Recommendations and reports. 70, 1-30, 2021. https://doi.org/10.15585/mmwr.rr7002a1

Barker D., Gillum K.T., Niemuth N.A., Kodihalli S.. Therapeutic efficacy of equine botulism heptavalent antitoxin against all seven botulinum neurotoxins in symptomatic guinea pigs. PloS one. 14, e0222670, 2019. https://doi.org/10.1371/journal.pone.0222670

Beliveau M., Anderson D., Barker D., Kodihalli S., Simard E., Hall C., Richardson J.S.. Exposure-Response Modeling and Simulation to Support Human Dosing of Botulism Antitoxin Heptavalent Product. Clinical pharmacology and therapeutics. 112, 171-180, 2022. https://doi.org/10.1002/cpt.2620

Zheng X., Wong G., Zhao Y., Wang H., He S., Bi Y., Chen W., Jin H., Gai W., Chu D., Cao Z., Wang C., Fan Q., Chi H., Gao Y., Wang T., Feng N., Yan F., Huang G., Zheng Y., N Li., Li Y., Qian J., Zou Y., Kobinger G., Gao G.F., Qiu X., Yang S., Xia X. Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection. Scientific reports. 6, 24179, 2016. https://doi.org/10.1038/srep24179

Wang H., Wong G., Zhu W., He S., Zhao Y., Yan F., Rahim M.N., Bi Y., Zhang Z., Cheng K., Jin H., Cao Z., Zheng X., Gai W., Bai J., Chen W., Zou Y., Gao Y., G Gao.F., Yang S., Xia X., Qiu X. Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease. Journal of virology. 93, e01548-18, 2019. https://doi.org/10.1128/JVI.01548-18

Hansda A., Biswas D., Bhatta A., Chakravorty N., Mukherjee G. Plasma therapy: a passive resistance against the deadliest. Human vaccines & immunotherapeutics. 18, 2006026, 2022. https://doi.org/10.1080/21645515.2021.2006026

Li E., Han Q., Bi J., Wei S., Wang S., Zhang Y., Liu J., Feng N., Wang T., J Wu., Yang S., Zhao Y., Liu B., Yan F., Xia X. Therapeutic equine hyperimmune antibodies with high and broad-spectrum neutralizing activity protect rodents against SARS-CoV-2 infection. Frontiers in immunology. 14, 1066730, 2023. https://doi.org/10.3389/fimmu.2023.1066730

Cunha L.E.R., Stolet A.A., Strauch M.A., Pereira V.A.R., Dumard C.H., Gomes A.M.O., Monteiro F.L., Higa L.M., Souza P.N.C., Fonseca J.G., Pontes F.E., Meirelles L.G.R., Albuquerque J.W.M., C Sacramento.Q., N Fintelman-Rodrigues., Lima T.M., Alvim R.G.F., Marsili F.F., Caldeira M.M., Zingali R.B., G. de Oliveira A.P., Souza T.M.L., Silva A.S., Muller R Rodrigues., D.D.R.F., Jesus da Costa L., Alves A.D.R., Pinto M.A., Oliveira A.C., Guedes H.L.M., Tanuri A., Castilho L.R., Silva J.L. Polyclonal F(ab')2 fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency. iScience. 24, 103315, 2021. https://doi.org/10.1016/j.isci.2021.103315

Andrade S.A., Batalha-Carvalho J.V., Curi R., Wen F.H., Covas D.T., Chudzinski-Tavassi A.M., Moro A.M. Equine Anti-SARS-CoV-2 Serum (ECIG) Binds to Mutated RBDs and N Proteins of Variants of Concern and Inhibits the Binding of RBDs to ACE-2 Receptor. Frontiers in immunology. 13, 871874, 2022. https://doi.org/10.3389/fimmu.2022.871874

Liu X., Liu Y., Jin X., He Z., Huang Z., Sun S., Gao Y., Li J., Ning Q., Xie Z., Jin N., Liu M. Rapidly developable therapeutic-grade equine immunoglobulin against the SARS-CoV-2 infection in rhesus macaques. Signal transduction and targeted therapy. 7, 219, 2022. https://doi.org/10.1038/s41392-022-01095-8

Lub M.Yu., Shevtsov A.N., Kozhukhov V.V., Logvinov S.V., Sedelnikov I.N., Kozlova T.N., Fokina V.V., inventors; Federal State Institution "48 Central Research Institute of the Ministry of Defense of the Russian Federation", assignee. Serum immunobiological preparation for emergency anthrax prevention and treatment. Russian Federation patent 2381037C1. 2010.

Mikhailov V.V., Borisevich N.A., Timankova A.D., Krasnyansky V.P., Potryvaeva N.V., Lebedinskaya E.V., Chernikova N.K., inventors; Virology Center of the Research Institute of Microbiology of the Ministry of Defense of the Russian Federation, assignee. Preparation containing immunoglobulin against abol fever from horse blood serum and liquid abol immunoglobulin. Russian Federation patent 2130318C1, 1999.

Shi B., Han H., Tan L., Liu Y., Yan F., Li B., Zheng N., Li M., Zhao L., Li H., Fan T., Zhang Z., Li X., Tian C., Zheng Y., He W., Zhao Z. Preparation of Equine Immunoglobulin F(ab′) 2 against Smallpox and Evaluation of its Immunoprotective Effect. Zoonoses. 3, e992, 2023. http://dx.doi.org/10.15212/ZOONOSES-2022-0048

Cohn E.J., Oncley J.L., Strong L.E., Hughes W.L., Armstrong S.H. Chemical, clinical, and immunological studies on the products of human plasma fractionation. I. The characterization of the protein fractions of human plasma. The Journal of clinical investigation. 23, 417-432, 1944. https://doi.org/10.1172/JCI101508

Cruz A.M., Oscar O.A., Dailin D.C., Oliver P.M. (2015). Caprylic Acid in the purification of horse tetanus IgG immunoglobulin. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology. Frontiers in Immunology. https://doi.org/10.3389/conf.fimmu.2015.05.00241

Al-Abdulla I., Casewell N.R., Landon J. Single-reagent one-step procedures for the purification of ovine IgG, F(ab')2 and Fab antivenoms by caprylic acid. Journal of immunological methods. 402, 15-22, 2014. https://doi.org/10.1016/j.jim.2013.11.001

Puvanakrishnan R., Bose S.M. Immobilization of pepsin on sand: preparation, characterization and application. Indian journal of biochemistry & biophysics. 21, 323-326, 1984.

Sitnik N.P. (2007). Development of a highly purified anti-rabies immunoglobulin preparation from horse plasma. Ufa, Ph.D. thesis in biology. pp. 20.

WHO Expert Consultation on Rabies: first report. Geneva, 2004, pp. 121.

Generalov S.V., Abramova E.G., Nikiforov A.K., Hramkova E.M., Shepelev I.A., Savitskaya L.V., Minaeva L.N., Galkina M.V., Miheeva T.A., Kochkalova N.N., Kireev M.N.. F(ab’)2-Fragments of Antirabic Immunoglobulin Production Using Immobilized Pepsin. Problems of especially dangerous infections. 97, 53-56, 2008.

Mótyán J.A., Tóth F., Tőzsér J. Research applications of proteolytic enzymes in molecular biology. Biomolecules. 3, 923-942, 2013. https://doi.org/10.3390/biom3040923

Miranda-Cruz A.R., Sánchez-Artigas R., Otero-Alfaro O., Góngora-Amores W., Cobos-Valdes D., Goya-Batista Y., Balboa-González J., Pérez-Martín O. Using the caprylic acid in obtaining the horse immunoglobulin anti tetanus toxin. VacciMonitor. 23, 63-72, 2014.

Borisevich S.V., Kutaev D.A., Rozhdestvensky E.V., Gordeev E.V., Khmelev A.L., Nazarov S.V., Melnikov S.A., Nimirskaya S.A., Chernikova N.K., Podkuiko V.N., inventors; Federal State Institution "48 Central Research Institute of the Ministry of Defense of the Russian Federation", assignee. Method of producing smallpox immunoglobulin from horse blood serum. Russian Federation patent 2770425C2. 2021.

Fernandes A., Kaundinya J.O., Daftary G., Saxena L., Banerjee S., Pattnaik P. Chromatographic purification of equine immunoglobulin G F(ab)2 from plasma. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 876, 109-115, 2008. https://doi.org/10.1016/j.jchromb.2008.10.030

Mateljak Lukačević S., Kurtović T., Lang Balija M., Brgles M., Steinberger S., Marchetti-Deschmann M., Halassy B. Quality-Related Properties of Equine Immunoglobulins Purified by Different Approaches. Toxins. 12, 798, 2020. https://doi.org/10.3390/toxins12120798

Sapsutthipas S., Leong P.K., Akesowan S., Pratanaphon R., Tan N.H., Ratanabanangkoon K. Effective equine immunization protocol for production of potent poly-specific antisera against Calloselasma rhodostoma, Cryptelytrops albolabris and Daboia siamensis. PLoS neglected tropical diseases. 9, e0003609, 2015. https://doi.org/10.1371/journal.pntd.0003609

de la Rosa G., Olvera F., Archundia I.G., Lomonte B., Alagón A., G. Corzo. Horse immunization with short-chain consensus α-neurotoxin generates antibodies against broad spectrum of elapid venomous species. Nature communications. 10, 3642, 2019. https://doi.org/10.1038/s41467-019-11639-2

Wang B., Liu G., Luo M., Zhang X., Wang Q., Zou S., Zhang F., Jin X., Zhang L. Preparation and Evaluation of a Horse Antiserum against the Venom of Sea Snake Hydrophis curtus from Hainan, China. Toxins. 14, 253, 2022. https://doi.org/10.3390/toxins14040253

Pucca M.B., Cerni F.A., Janke R., Bermúdez-Méndez E., Ledsgaard L., Barbosa J.E., Laustsen A.H. History of Envenoming Therapy and Current Perspectives. Frontiers in immunology. 10, 1598, 2019. https://doi.org/10.3389/fimmu.2019.01598

Dart R.C., Bush S.P., Heard K., Arnold T.C., Sutter M., Campagne D., Holstege C.P., Seifert S.A., Lo J.C.Y., Quan D., S Borron., Meurer D.A., Burnham R.I., McNally J., Garcia-Ubbelohde W., Anderson V.E. The Efficacy of Antivenin Latrodectus (Black Widow) Equine Immune F(ab')2 Versus Placebo in the Treatment of Latrodectism: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial. Annals of emergency medicine. 74, 439-449, 2019. https://doi.org/10.1016/j.annemergmed.2019.02.007

Mori S., Horita A., Ginnaga A., Miyatsu Y., Sawabe K., Matsumura T., Ato M., Yamamoto A., Shibayama K., Arai S., Yamagishi T., Takahashi M., Taki H., Hifumi T. Venom and Antivenom of the Redback Spider (Latrodectus hasseltii) in Japan. Part II. Experimental Production of Equine Antivenom against the Redback Spider. Japanese journal of infectious diseases. 70, 635-641, 2017. https://doi.org/10.7883/yoken.JJID.2017.125

Manteca Vilanova X., Beaver B., Uldahl M., Turner P.V. Recommendations for Ensuring Good Welfare of Horses Used for Industrial Blood, Serum, or Urine Production. Animals. 11, 1466, 2021. https://doi.org/10.3390/ani11051466

Freund J., Thomson K.J. Antibody formation and sensitization with the aid of adjuvants. Journal of immunology. 60, 383-398, 1948.

Cox J.C., Liefman C.E., Premier R.R., Chandler H.M., Herrington R.W., Middleton H.D., Hurrell J.G. Immune response and reactions to various dose regimens for raising hyperimmune antisera in sheep. Veterinary immunology and immunopathology. 7, 65-72, 1984. https://doi.org/10.1016/0165-2427(84)90028-x

Krasnopolsky Yu.M., Pylypenko D.M. (2022). Pharmaceutical biotechnology: present and future. Kharkiv, Printing House “Madrid”. pp. 151.

Krasnopolsky Y., Pylypenko D. Licensed liposomal vaccines and adjuvants in the antigen delivery system. Biotechnologia. 103, 409-423, 2022. https://doi.org/10.5114/bta.2022.120709

Buer A.W. A method for production of high-titre tetanus serum. Acta Pathologica Microbiologica Scandinavica. 23, 293-298, 1946. https://doi.org/10.1111/j.1699-0463.1946.tb00543.x

Pan X., Wu Y., Wang W., Zhang L., Xiao G. Development of horse neutralizing immunoglobulin and immunoglobulin fragments against Junín virus. Antiviral research. 174, 104666, 2020. https://doi.org/10.1016/j.antiviral.2019.104666

Mashin V.V., Sergeev A.N., Martynova N.N., Oganov M.D., Sergeev A.A., Kataeva V.V., Zagidullin N.V. Ensuring Viral Safety of Equine Immunoglobulins during Production. Pharmaceutical chemistry journal. 56, 283-288, 2022. https://doi.org/10.1007/s11094-022-02632-z

Mottate K., Yokote H., Mori S., Horita A., Miyatsu Y., Torii Y., Kozaki S., Iwaki M., Takahashi M., Ginnaga A.. Retrospective survey to evaluate the safety and efficacy of Japanese botulinum antitoxin therapy in Japan. Toxicon : official journal of the International Society on Toxinology. 110, 12-18, 2016. https://doi.org/10.1016/j.toxicon.2015.11.010

Moreira-Soto A., Arguedas M., Brenes H., Buján W., Corrales-Aguilar E., Díaz C., Echeverri A., Flores-Díaz M., Gómez A., Hernández A., Herrera M., León G., Macaya R., Kühne A., Molina-Mora J.A., Mora J., Sanabria A., Sánchez A., Sánchez L., Segura Á., Segura E., Solano D., Soto C., Stynoski J.L., Vargas M., Villalta M., Reusken C.B.E.M., Drosten C., Gutiérrez J.M., Alape-Girón A., Drexler J.F. High Efficacy of Therapeutic Equine Hyperimmune Antibodies Against SARS-CoV-2 Variants of Concern. Frontiers in medicine. 8, 735853, 2021. https://doi.org/10.3389/fmed.2021.735853

Bozheyeva G., Kunakbayev Y., Yeleukenov D. (1999). Former Soviet biological weapons facilities in Kazakhstan : past, present, and future. USA, Center for Nonproliferation Studies, Monterey Institute of International Studies, Monterey, CA. pp. 29.

Expanded Access Investigational New Drug (IND) Application Protocol: Use of Diphtheria Antitoxin (DAT) for Possible Diphtheria Cases BB-IND 11184. Version Number 12.0. Centers for Disease Control and Prevention, Atlanta, 2023, pp. 19.

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