Development and characterization of two equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19.

1. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin.. Nature 2020 Mar;579(7798):270-273.
   doi: 10.1038/s41586-020-2012-7pmc: PMC7095418pubmed: 32015507google scholar: lookup
2. Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W. A Novel Coronavirus from Patients with Pneumonia in China, 2019.. N Engl J Med 2020 Feb 20;382(8):727-733.
   doi: 10.1056/NEJMoa2001017pmc: PMC7092803pubmed: 31978945google scholar: lookup
3. Tanne JH. Covid-19: FDA approves use of convalescent plasma to treat critically ill patients.. BMJ 2020 Mar 26;368:m1256.
   pubmed: 32217555doi: 10.1136/bmj.m1256google scholar: lookup
4. Phua J, Weng L, Ling L, Egi M, Lim CM, Divatia JV, Shrestha BR, Arabi YM, Ng J, Gomersall CD, Nishimura M, Koh Y, Du B. Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations.. Lancet Respir Med 2020 May;8(5):506-517.
   doi: 10.1016/S2213-2600(20)30161-2pmc: PMC7198848pubmed: 32272080google scholar: lookup
5. Tortorici MA, Veesler D. Structural insights into coronavirus entry.. Adv Virus Res 2019;105:93-116.
   pmc: PMC7112261pubmed: 31522710doi: 10.1016/bs.aivir.2019.08.002google scholar: lookup
6. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein.. Cell 2020 Apr 16;181(2):281-292.e6.
   doi: 10.1016/j.cell.2020.02.058pmc: PMC7102599pubmed: 32155444google scholar: lookup
7. Zhang Z, Xie YW, Hong J, Zhang X, Kwok SY, Huang X, Wong SW, Wong BL. Purification of severe acute respiratory syndrome hyperimmune globulins for intravenous injection from convalescent plasma.. Transfusion 2005 Jul;45(7):1160-4.
   doi: 10.1111/j.1537-2995.2005.00179.xpmc: PMC7201861pubmed: 15987362google scholar: lookup
8. Ainsworth S, Menzies S, Pleass RJ. Animal derived antibodies should be considered alongside convalescent human plasma to deliver treatments for COVID-19.. Wellcome Open Res 2020;5:115.
   doi: 10.12688/wellcomeopenres.15990.1google scholar: lookup
9. Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19.. J Clin Invest 2020 Apr 1;130(4):1545-1548.
   doi: 10.1172/JCI138003pmc: PMC7108922pubmed: 32167489google scholar: lookup
10. de Alwis R, Chen S, Gan ES, Ooi EE. Impact of immune enhancement on Covid-19 polyclonal hyperimmune globulin therapy and vaccine development.. EBioMedicine 2020 May;55:102768.
    doi: 10.1016/j.ebiom.2020.102768pmc: PMC7161485pubmed: 32344202google scholar: lookup
11. Liu STH, Lin HM, Baine I, Wajnberg A, Gumprecht JP, Rahman F, Rodriguez D, Tandon P, Bassily-Marcus A, Bander J, Sanky C, Dupper A, Zheng A, Nguyen FT, Amanat F, Stadlbauer D, Altman DR, Chen BK, Krammer F, Mendu DR, Firpo-Betancourt A, Levin MA, Bagiella E, Casadevall A, Cordon-Cardo C, Jhang JS, Arinsburg SA, Reich DL, Aberg JA, Bouvier NM. Convalescent plasma treatment of severe COVID-19: a propensity score-matched control study.. Nat Med 2020 Nov;26(11):1708-1713.
    doi: 10.1038/s41591-020-1088-9pubmed: 32934372google scholar: lookup
12. Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, Zhou M, Chen L, Meng S, Hu Y, Peng C, Yuan M, Huang J, Wang Z, Yu J, Gao X, Wang D, Yu X, Li L, Zhang J, Wu X, Li B, Xu Y, Chen W, Peng Y, Hu Y, Lin L, Liu X, Huang S, Zhou Z, Zhang L, Wang Y, Zhang Z, Deng K, Xia Z, Gong Q, Zhang W, Zheng X, Liu Y, Yang H, Zhou D, Yu D, Hou J, Shi Z, Chen S, Chen Z, Zhang X, Yang X. Effectiveness of convalescent plasma therapy in severe COVID-19 patients.. Proc Natl Acad Sci U S A 2020 Apr 28;117(17):9490-9496.
    doi: 10.1073/pnas.2004168117pmc: PMC7196837pubmed: 32253318google scholar: lookup
13. Ahn JY, Sohn Y, Lee SH, Cho Y, Hyun JH, Baek YJ, Jeong SJ, Kim JH, Ku NS, Yeom JS, Roh J, Ahn MY, Chin BS, Kim YS, Lee H, Yong D, Kim HO, Kim S, Choi JY. Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea.. J Korean Med Sci 2020 Apr 13;35(14):e149.
    doi: 10.3346/jkms.2020.35.e2pmc: PMC7152526pubmed: 32281317google scholar: lookup
14. Shen C, Wang Z, Zhao F, Yang Y, Li J, Yuan J, Wang F, Li D, Yang M, Xing L, Wei J, Xiao H, Yang Y, Qu J, Qing L, Chen L, Xu Z, Peng L, Li Y, Zheng H, Chen F, Huang K, Jiang Y, Liu D, Zhang Z, Liu Y, Liu L. Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma.. JAMA 2020 Apr 28;323(16):1582-1589.
    doi: 10.1001/jama.2020.4783pmc: PMC7101507pubmed: 32219428google scholar: lookup
15. Joyner MJ. Evidence favouring the efficacy of convalescent plasma for COVID-19 therapy.. medRxiv 2020.07.29.20162917 (2020).
16. Mair-Jenkins J, Saavedra-Campos M, Baillie JK, Cleary P, Khaw FM, Lim WS, Makki S, Rooney KD, Nguyen-Van-Tam JS, Beck CR. The effectiveness of convalescent plasma and hyperimmune immunoglobulin for the treatment of severe acute respiratory infections of viral etiology: a systematic review and exploratory meta-analysis.. J Infect Dis 2015 Jan 1;211(1):80-90.
    doi: 10.1093/infdis/jiu396pmc: PMC4264590pubmed: 25030060google scholar: lookup
17. Ali MB. Treating severe acute respiratory syndrome with hyperimmune globulins.. Hong Kong Med J 2003 Oct;9(5):391-2.
    pubmed: 14530539
18. Burnouf T, Radosevich M. Treatment of severe acute respiratory syndrome with convalescent plasma.. Hong Kong Med J 2003 Aug;9(4):309; author reply 310.
    pubmed: 12904626
19. Luo D, Ni B, Zhao G, Jia Z, Zhou L, Pacal M, Zhang L, Zhang S, Xing L, Lin Z, Wang L, Li J, Liang Y, Shi X, Zhao T, Zou L, Wu Y, Wang X. Protection from infection with severe acute respiratory syndrome coronavirus in a Chinese hamster model by equine neutralizing F(ab')2.. Viral Immunol 2007 Sep;20(3):495-502.
    doi: 10.1089/vim.2007.0038pubmed: 17931120google scholar: lookup
20. Lu JH, Guo ZM, Han WY, Wang GL, Zhang DM, Wang YF, Sun SY, Yang QH, Zheng HY, Wong BL, Zhong NS. Preparation and development of equine hyperimmune globulin F(ab')2 against severe acute respiratory syndrome coronavirus.. Acta Pharmacol Sin 2005 Dec;26(12):1479-84.
    doi: 10.1111/j.1745-7254.2005.00210.xpmc: PMC7091834pubmed: 16297347google scholar: lookup
21. Wang X, Ni B, Du X, Zhao G, Gao W, Shi X, Zhang S, Zhang L, Wang D, Luo D, Xing L, Jiang H, Li W, Jiang M, Mao L, He Y, Xiao Y, Wu Y. Protection of mammalian cells from severe acute respiratory syndrome coronavirus infection by equine neutralizing antibody.. Antivir Ther 2005;10(5):681-90.
    pubmed: 16152762
22. Zhou L, Ni B, Luo D, Zhao G, Jia Z, Zhang L, Lin Z, Wang L, Zhang S, Xing L, Li J, Liang Y, Shi X, Zhao T, Zhou L, Wu Y, Wang X. Inhibition of infection caused by severe acute respiratory syndrome-associated coronavirus by equine neutralizing antibody in aged mice.. Int Immunopharmacol 2007 Mar;7(3):392-400.
    doi: 10.1016/j.intimp.2006.10.009pmc: PMC7106264pubmed: 17276898google scholar: lookup
23. Zhao G, Ni B, Jiang H, Luo D, Pacal M, Zhou L, Zhang L, Xing L, Zhang L, Jia Z, Lin Z, Wang L, Li J, Liang Y, Shi X, Zhao T, Zhou L, Wu Y, Wang X. Inhibition of severe acute respiratory syndrome-associated coronavirus infection by equine neutralizing antibody in golden Syrian hamsters.. Viral Immunol 2007 Spring;20(1):197-205.
    doi: 10.1089/vim.2006.0064pubmed: 17425434google scholar: lookup
24. Zhao Y, Wang C, Qiu B, Li C, Wang H, Jin H, Gai W, Zheng X, Wang T, Sun W, Yan F, Gao Y, Wang Q, Yan J, Chen L, Perlman S, Zhong N, Zhao J, Yang S, Xia X. Passive immunotherapy for Middle East Respiratory Syndrome coronavirus infection with equine immunoglobulin or immunoglobulin fragments in a mouse model.. Antiviral Res 2017 Jan;137:125-130.
    doi: 10.1016/j.antiviral.2016.11.016pmc: PMC7113855pubmed: 27890674google scholar: lookup
25. Pan X, Zhou P, Fan T, Wu Y, Zhang J, Shi X, Shang W, Fang L, Jiang X, Shi J, Sun Y, Zhao S, Gong R, Chen Z, Xiao G. Immunoglobulin fragment F(ab')(2) against RBD potently neutralizes SARS-CoV-2 in vitro.. Antiviral Res 2020 Oct;182:104868.
    doi: 10.1016/j.antiviral.2020.104868pmc: PMC7351055pubmed: 32659292google scholar: lookup
26. Zylberman V, Sanguineti S, Pontoriero AV, Higa SV, Cerutti ML, Morrone Seijo SM, Pardo R, Muñoz L, Acuña Intrieri ME, Alzogaray VA, Avaro MM, Benedetti E, Berguer PM, Bocanera L, Bukata L, Bustelo MS, Campos AM, Colonna M, Correa E, Cragnaz L, Dattero ME, Dellafiore M, Foscaldi S, González JV, Guerra LL, Klinke S, Labanda MS, Lauché C, López JC, Martínez AM, Otero LH, Peyric EH, Ponziani PF, Ramondino R, Rinaldi J, Rodríguez S, Russo JE, Russo ML, Saavedra SL, Seigelchifer M, Sosa S, Vilariño C, López Biscayart P, Corley E, Spatz L, Baumeister EG, Goldbaum FA. Development of a hyperimmune equine serum therapy for COVID-19 in Argentina.. Medicina (B Aires) 2020;80 Suppl 3:1-6.
    pubmed: 32658841
27. Cunha LE. Equine hyperimmune globulin raised against the SARS-CoV-2 spike glycoprotein has extremely high neutralizing titers.. bioRxiv 2020.08.17.254375 (2020).
28. León G, Vargas M, Segura Á, Herrera M, Villalta M, Sánchez A, Solano G, Gómez A, Sánchez M, Estrada R, Gutiérrez JM. Current technology for the industrial manufacture of snake antivenoms.. Toxicon 2018 Sep 1;151:63-73.
    doi: 10.1016/j.toxicon.2018.06.084pubmed: 29959968google scholar: lookup
29. Angulo Y, Estrada R, María Gutiérrez J. Effects of bleeding in horses inmunized with snake venoms for antivenom production.. Rev. Biol. Trop. 1997;45:1215–1221.
30. Rojas G, Jiménez JM, Gutiérrez JM. Caprylic acid fractionation of hyperimmune horse plasma: description of a simple procedure for antivenom production.. Toxicon 1994 Mar;32(3):351-63.
    doi: 10.1016/0041-0101(94)90087-6pubmed: 8016856google scholar: lookup
31. Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.. Nature 1970 Aug 15;227(5259):680-5.
    doi: 10.1038/227680a0pubmed: 5432063google scholar: lookup
32. PARVIN R, PANDE SV, VENKITASUBRAMANIAN TA. ON THE COLORIMETRIC BIURET METHOD OF PROTEIN DETERMINATION.. Anal Biochem 1965 Aug;12:219-29.
    doi: 10.1016/0003-2697(65)90085-0pubmed: 14340012google scholar: lookup
33. USP (United States Pharmacopoeia). USP 37/NF32.. U. S. Pharmacopeial Convention, Rockville, United States. (2014).
34. Lacoste RJ, Venable S, Stone JC. Modified 4-aminoantipyrine colorimetric method for phenols: application to an acrylic monomer.. Anal. Chem. 1959;31:1246–1249.
    doi: 10.1021/ac60151a007google scholar: lookup
35. Herrera M, Meneses F, Gutiérrez JM, León G. Development and validation of a reverse phase HPLC method for the determination of caprylic acid in formulations of therapeutic immunoglobulins and its application to antivenom production.. Biologicals 2009 Aug;37(4):230-4.
    doi: 10.1016/j.biologicals.2009.02.020pubmed: 19375941google scholar: lookup
36. Solano G, Gómez A, León G. Assessing endotoxins in equine-derived snake antivenoms: Comparison of the USP pyrogen test and the Limulus Amoebocyte Lysate assay (LAL).. Toxicon 2015 Oct;105:13-8.
    doi: 10.1016/j.toxicon.2015.08.015pubmed: 26325294google scholar: lookup
37. Corrales-Aguilar E, Trilling M, Reinhard H, Mercé-Maldonado E, Widera M, Schaal H, Zimmermann A, Mandelboim O, Hengel H. A novel assay for detecting virus-specific antibodies triggering activation of Fcγ receptors.. J Immunol Methods 2013 Jan 31;387(1-2):21-35.
    doi: 10.1016/j.jim.2012.09.006pubmed: 23023090google scholar: lookup
38. Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research.. PLoS Biol 2010 Jun 29;8(6):e1000412.
    doi: 10.1371/journal.pbio.1000412pmc: PMC2893951pubmed: 20613859google scholar: lookup
39. . CIOMS International Guiding Principles for Biomedical Research Involving Animals.. Altern Lab Anim 1985 Jun;12(4):ii-.
    pubmed: 11653736
40. Wang Q, Zhang Y, Wu L, Niu S, Song C, Zhang Z, Lu G, Qiao C, Hu Y, Yuen KY, Wang Q, Zhou H, Yan J, Qi J. Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2.. Cell 2020 May 14;181(4):894-904.e9.
    doi: 10.1016/j.cell.2020.03.045pmc: PMC7144619pubmed: 32275855google scholar: lookup
41. Jiang S, Du L, Shi Z. An emerging coronavirus causing pneumonia outbreak in Wuhan, China: calling for developing therapeutic and prophylactic strategies.. Emerg Microbes Infect 2020;9(1):275-277.
    doi: 10.1080/22221751.2020.1723441pmc: PMC7033706pubmed: 32005086google scholar: lookup
42. Wang H, Wong G, Zhu W, He S, Zhao Y, Yan F, Rahim MN, Bi Y, Zhang Z, Cheng K, Jin H, Cao Z, Zheng X, Gai W, Bai J, Chen W, Zou Y, Gao Y, Gao GF, Yang S, Xia X, Qiu X. Equine-Origin Immunoglobulin Fragments Protect Nonhuman Primates from Ebola Virus Disease.. J Virol 2019 Mar 1;93(5).
    pmc: PMC6384060pubmed: 30541860doi: 10.1128/jvi.01548-18google scholar: lookup
43. Hwang WC, Lin Y, Santelli E, Sui J, Jaroszewski L, Stec B, Farzan M, Marasco WA, Liddington RC. Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.. J Biol Chem 2006 Nov 10;281(45):34610-6.
    doi: 10.1074/jbc.M603275200pmc: PMC7981188pubmed: 16954221google scholar: lookup
44. Liu L, Wang P, Nair MS, Yu J, Rapp M, Wang Q, Luo Y, Chan JF, Sahi V, Figueroa A, Guo XV, Cerutti G, Bimela J, Gorman J, Zhou T, Chen Z, Yuen KY, Kwong PD, Sodroski JG, Yin MT, Sheng Z, Huang Y, Shapiro L, Ho DD. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike.. Nature 2020 Aug;584(7821):450-456.
    doi: 10.1038/s41586-020-2571-7pubmed: 32698192google scholar: lookup
45. Du L, He Y, Zhou Y, Liu S, Zheng BJ, Jiang S. The spike protein of SARS-CoV--a target for vaccine and therapeutic development.. Nat Rev Microbiol 2009 Mar;7(3):226-36.
    doi: 10.1038/nrmicro2090pmc: PMC2750777pubmed: 19198616google scholar: lookup
46. Yu IM, Oldham ML, Zhang J, Chen J. Crystal structure of the severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein dimerization domain reveals evolutionary linkage between corona- and arteriviridae.. J Biol Chem 2006 Jun 23;281(25):17134-17139.
    doi: 10.1074/jbc.M602107200pmc: PMC7946579pubmed: 16627473google scholar: lookup
47. Liu L, Liu W, Zheng Y, Jiang X, Kou G, Ding J, Wang Q, Huang Q, Ding Y, Ni W, Wu W, Tang S, Tan L, Hu Z, Xu W, Zhang Y, Zhang B, Tang Z, Zhang X, Li H, Rao Z, Jiang H, Ren X, Wang S, Zheng S. A preliminary study on serological assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 238 admitted hospital patients.. Microbes Infect 2020 May-Jun;22(4-5):206-211.
    doi: 10.1016/j.micinf.2020.05.008pmc: PMC7233230pubmed: 32425648google scholar: lookup
48. Long QX, Tang XJ, Shi QL, Li Q, Deng HJ, Yuan J, Hu JL, Xu W, Zhang Y, Lv FJ, Su K, Zhang F, Gong J, Wu B, Liu XM, Li JJ, Qiu JF, Chen J, Huang AL. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.. Nat Med 2020 Aug;26(8):1200-1204.
    doi: 10.1038/s41591-020-0965-6pubmed: 32555424google scholar: lookup
49. Long QX, Liu BZ, Deng HJ, Wu GC, Deng K, Chen YK, Liao P, Qiu JF, Lin Y, Cai XF, Wang DQ, Hu Y, Ren JH, Tang N, Xu YY, Yu LH, Mo Z, Gong F, Zhang XL, Tian WG, Hu L, Zhang XX, Xiang JL, Du HX, Liu HW, Lang CH, Luo XH, Wu SB, Cui XP, Zhou Z, Zhu MM, Wang J, Xue CJ, Li XF, Wang L, Li ZJ, Wang K, Niu CC, Yang QJ, Tang XJ, Zhang Y, Liu XM, Li JJ, Zhang DC, Zhang F, Liu P, Yuan J, Li Q, Hu JL, Chen J, Huang AL. Antibody responses to SARS-CoV-2 in patients with COVID-19.. Nat Med 2020 Jun;26(6):845-848.
    doi: 10.1038/s41591-020-0897-1pubmed: 32350462google scholar: lookup
50. Guo L, Ren L, Yang S, Xiao M, Chang D, Yang F, Dela Cruz CS, Wang Y, Wu C, Xiao Y, Zhang L, Han L, Dang S, Xu Y, Yang QW, Xu SY, Zhu HD, Xu YC, Jin Q, Sharma L, Wang L, Wang J. Profiling Early Humoral Response to Diagnose Novel Coronavirus Disease (COVID-19).. Clin Infect Dis 2020 Jul 28;71(15):778-785.
    doi: 10.1093/cid/ciaa310pmc: PMC7184472pubmed: 32198501google scholar: lookup
51. Zhao J. Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019.. Clin. Infect. Dis. 2020;26:845–848.
52. To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, Yip CC, Cai JP, Chan JM, Chik TS, Lau DP, Choi CY, Chen LL, Chan WM, Chan KH, Ip JD, Ng AC, Poon RW, Luo CT, Cheng VC, Chan JF, Hung IF, Chen Z, Chen H, Yuen KY. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study.. Lancet Infect Dis 2020 May;20(5):565-574.
    doi: 10.1016/S1473-3099(20)30196-1pmc: PMC7158907pubmed: 32213337google scholar: lookup
53. Schoeman D, Fielding BC. Coronavirus envelope protein: current knowledge.. Virol J 2019 May 27;16(1):69.
    doi: 10.1186/s12985-019-1182-0pmc: PMC6537279pubmed: 31133031google scholar: lookup
54. Siu YL, Teoh KT, Lo J, Chan CM, Kien F, Escriou N, Tsao SW, Nicholls JM, Altmeyer R, Peiris JS, Bruzzone R, Nal B. The M, E, and N structural proteins of the severe acute respiratory syndrome coronavirus are required for efficient assembly, trafficking, and release of virus-like particles.. J Virol 2008 Nov;82(22):11318-30.
    doi: 10.1128/JVI.01052-08pmc: PMC2573274pubmed: 18753196google scholar: lookup
55. León G, Sánchez L, Hernández A, Villalta M, Herrera M, Segura A, Estrada R, Gutiérrez JM. Immune response towards snake venoms.. Inflamm Allergy Drug Targets 2011 Oct;10(5):381-98.
    doi: 10.2174/187152811797200605pubmed: 21824081google scholar: lookup
56. WHO (World Health Organization). WHO Guidelines for the Production , Control and Regulation of Snake Antivenom Immunoglobulins.. WHO Technical Report Series Annex 5 No. 1004. Geneva (2017).
57. Abubakar IS, Abubakar SB, Habib AG, Nasidi A, Durfa N, Yusuf PO, Larnyang S, Garnvwa J, Sokomba E, Salako L, Theakston RD, Juszczak E, Alder N, Warrell DA. Randomised controlled double-blind non-inferiority trial of two antivenoms for saw-scaled or carpet viper (Echis ocellatus) envenoming in Nigeria.. PLoS Negl Trop Dis 2010 Jul 27;4(7):e767.
    doi: 10.1371/journal.pntd.0000767pmc: PMC2910709pubmed: 20668549google scholar: lookup
58. Otero R, Gutiérrez JM, Rojas G, Núñez V, Díaz A, Miranda E, Uribe AF, Silva JF, Ospina JG, Medina Y, Toro MF, García ME, León G, García M, Lizano S, De La Torre J, Márquez J, Mena Y, González N, Arenas LC, Puzón A, Blanco N, Sierra A, Espinal ME, Lozano R. A randomized blinded clinical trial of two antivenoms, prepared by caprylic acid or ammonium sulphate fractionation of IgG, in Bothrops and Porthidium snake bites in Colombia: correlation between safety and biochemical characteristics of antivenoms.. Toxicon 1999 Jun;37(6):895-908.
    doi: 10.1016/S0041-0101(98)00220-7pubmed: 10340829google scholar: lookup
59. Otero-Patiño R, Segura A, Herrera M, Angulo Y, León G, Gutiérrez JM, Barona J, Estrada S, Pereañez A, Quintana JC, Vargas LJ, Gómez JP, Díaz A, Suárez AM, Fernández J, Ramírez P, Fabra P, Perea M, Fernández D, Arroyo Y, Betancur D, Pupo L, Córdoba EA, Ramírez CE, Arrieta AB, Rivero A, Mosquera DC, Conrado NL, Ortiz R. Comparative study of the efficacy and safety of two polyvalent, caprylic acid fractionated [IgG and F(ab')2] antivenoms, in Bothrops asper bites in Colombia.. Toxicon 2012 Feb;59(2):344-55.
    doi: 10.1016/j.toxicon.2011.11.017pubmed: 22146491google scholar: lookup
60. Mpandi M, Schmutz P, Legrand E, Duc R, Geinoz J, Henzelin-Nkubana C, Giorgia S, Clerc O, Genoud D, Weber T. Partitioning and inactivation of viruses by the caprylic acid precipitation followed by a terminal pasteurization in the manufacturing process of horse immunoglobulins.. Biologicals 2007 Oct;35(4):335-41.
    doi: 10.1016/j.biologicals.2007.02.004pubmed: 17470396google scholar: lookup
61. Caricati CP, Oliveira-Nascimento L, Yoshida JT, Caricati AT, Raw I, Stephano MA. Safety of snake antivenom immunoglobulins: efficacy of viral inactivation in a complete downstream process.. Biotechnol Prog 2013 Jul-Aug;29(4):972-9.
    doi: 10.1002/btpr.1758pmc: PMC7161767pubmed: 23804299google scholar: lookup
62. 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.
    doi: 10.1016/j.toxicon.2013.09.010pubmed: 24055551google scholar: lookup
63. Bolles M, Deming D, Long K, Agnihothram S, Whitmore A, Ferris M, Funkhouser W, Gralinski L, Totura A, Heise M, Baric RS. A double-inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge.. J Virol 2011 Dec;85(23):12201-15.
    doi: 10.1128/JVI.06048-11pmc: PMC3209347pubmed: 21937658google scholar: lookup
64. Iwasaki A, Yang Y. The potential danger of suboptimal antibody responses in COVID-19.. Nat Rev Immunol 2020 Jun;20(6):339-341.
    doi: 10.1038/s41577-020-0321-6pmc: PMC7187142pubmed: 32317716google scholar: lookup
65. van Erp EA, Luytjes W, Ferwerda G, van Kasteren PB. Fc-Mediated Antibody Effector Functions During Respiratory Syncytial Virus Infection and Disease.. Front Immunol 2019;10:548.
    doi: 10.3389/fimmu.2019.00548pmc: PMC6438959pubmed: 30967872google scholar: lookup
66. Yip MS, Leung HL, Li PH, Cheung CY, Dutry I, Li D, Daëron M, Bruzzone R, Peiris JS, Jaume M. Antibody-dependent enhancement of SARS coronavirus infection and its role in the pathogenesis of SARS.. Hong Kong Med J 2016 Jun;22(3 Suppl 4):25-31.
    pubmed: 27390007
67. Wang Q, Zhang L, Kuwahara K, Li L, Liu Z, Li T, Zhu H, Liu J, Xu Y, Xie J, Morioka H, Sakaguchi N, Qin C, Liu G. Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates.. ACS Infect Dis 2016 May 13;2(5):361-76.
    doi: 10.1021/acsinfecdis.6b00006pmc: PMC7075522pubmed: 27627203google scholar: lookup
68. Jaume M, Yip MS, Cheung CY, Leung HL, Li PH, Kien F, Dutry I, Callendret B, Escriou N, Altmeyer R, Nal B, Daëron M, Bruzzone R, Peiris JS. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway.. J Virol 2011 Oct;85(20):10582-97.
    doi: 10.1128/JVI.00671-11pmc: PMC3187504pubmed: 21775467google scholar: lookup
69. Liu L, Wei Q, Lin Q, Fang J, Wang H, Kwok H, Tang H, Nishiura K, Peng J, Tan Z, Wu T, Cheung KW, Chan KH, Alvarez X, Qin C, Lackner A, Perlman S, Yuen KY, Chen Z. Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection.. JCI Insight 2019 Feb 21;4(4).
    doi: 10.1172/jci.insight.123158pmc: PMC6478436pubmed: 30830861google scholar: lookup
70. Quinlan BD. The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement.. SSRN 2020.
71. Xu Y, Jia Z, Zhou L, Wang L, Li J, Liang Y, Zhao T, Ni B, Wu Y. Evaluation of the safety, immunogenicity and pharmacokinetics of equine anti-SARS-CoV F(ab')(2) in macaque.. Int Immunopharmacol 2007 Dec 15;7(13):1834-40.
    doi: 10.1016/j.intimp.2007.09.011pmc: PMC7106090pubmed: 17996696google scholar: lookup
72. Segura A, Herrera M, González E, Vargas M, Solano G, Gutiérrez JM, León G. Stability of equine IgG antivenoms obtained by caprylic acid precipitation: towards a liquid formulation stable at tropical room temperature.. Toxicon 2009 May;53(6):609-15.
    doi: 10.1016/j.toxicon.2009.01.012pubmed: 19673074google scholar: lookup

Citations

1. Abavisani M, Rahimian K, Mahdavi B, Tokhanbigli S, Mollapour Siasakht M, Farhadi A, Kodori M, Mahmanzar M, Meshkat Z. Mutations in SARS-CoV-2 structural proteins: a global analysis. Virol J 2022 Dec 18;19(1):220.
   doi: 10.1186/s12985-022-01951-7pubmed: 36528612google scholar: lookup
2. Andrade SA, Batalha-Carvalho JV, Curi R, Wen FH, Covas DT, Chudzinski-Tavassi AM, Moro AM. 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. Front Immunol 2022;13:871874.
   doi: 10.3389/fimmu.2022.871874pubmed: 35898497google scholar: lookup
3. Buyukozkan M, Alvarez-Mulett S, Racanelli AC, Schmidt F, Batra R, Hoffman KL, Sarwath H, Engelke R, Gomez-Escobar L, Simmons W, Benedetti E, Chetnik K, Zhang G, Schenck E, Suhre K, Choi JJ, Zhao Z, Racine-Brzostek S, Yang HS, Choi ME, Choi AMK, Cho SJ, Krumsiek J. Integrative metabolomic and proteomic signatures define clinical outcomes in severe COVID-19. iScience 2022 Jul 15;25(7):104612.
   doi: 10.1016/j.isci.2022.104612pubmed: 35756895google scholar: lookup
4. Strohl WR, Ku Z, An Z, Carroll SF, Keyt BA, Strohl LM. Passive Immunotherapy Against SARS-CoV-2: From Plasma-Based Therapy to Single Potent Antibodies in the Race to Stay Ahead of the Variants. BioDrugs 2022 May;36(3):231-323.
   doi: 10.1007/s40259-022-00529-7pubmed: 35476216google scholar: lookup
5. Gupta D, Ahmed F, Tandel D, Parthasarathy H, Vedagiri D, Sah V, Krishna Mohan B, Khan RA, Kondiparthi C, Savari P, Jain S, Reddy S, Kumar JM, Khan N, Harshan KH. Equine immunoglobulin fragment F(ab')(2) displays high neutralizing capability against multiple SARS-CoV-2 variants. Clin Immunol 2022 Apr;237:108981.
   doi: 10.1016/j.clim.2022.108981pubmed: 35306171google scholar: lookup
6. Botosso VF, Jorge SAC, Astray RM, de Sá Guimarães AM, Mathor MB, de Carneiro PDS, Durigon EL, Covas D, de Oliveira DBL, das Neves Oliveira R, Maria DA, Eto SF, Gallina NMF, Pidde G, Squaiella-Baptistão CC, Silva DT, Villas-Boas IM, Fernandes DC, Auada AVV, Banari AC, de Souza Filho AF, Bianconi C, de Agostini Utescher CL, Oliveira DCA, Mariano DOC, Barbosa FF, Rondon G, Kapronezai J, da Silva JG, Goldfeder MB, Comone P, Junior REC, Pereira TTS, Wen FH, Tambourgi DV, Chudzinski-Tavassi AM. Anti-SARS-CoV-2 equine F (Ab')(2) immunoglobulin as a possible therapy for COVID-19. Sci Rep 2022 Mar 10;12(1):3890.
   doi: 10.1038/s41598-022-07793-1pubmed: 35273234google scholar: lookup
7. González Viacava MB, Varese A, Mazzitelli I, Lanari L, Ávila L, García Vampa MJ, Geffner J, Cascone O, Dokmetjian JC, de Roodt AR, Fingermann M. Immune Maturation Effects on Viral Neutralization and Avidity of Hyperimmunized Equine Anti-SARS-CoV-2 Sera. Antibodies (Basel) 2022 Jan 2;11(1).
   doi: 10.3390/antib11010003pubmed: 35076465google scholar: lookup
8. Rojas-Jiménez G, Solano D, Segura Á, Sánchez A, Chaves-Araya S, Herrera M, Vargas M, Cerdas M, Calvo G, Alfaro J, Molina S, Bolaños K, Moreira-Soto A, Villalta M, Sánchez A, Cordero D, Durán G, Solano G, Gómez A, Hernández A, Sánchez L, Vargas M, Drexler JF, Alape-Girón A, Díaz C, León G. In vitro Characterization of Anti-SARS-CoV-2 Intravenous Immunoglobulins (IVIg) Produced From Plasma of Donors Immunized With the BNT162b2 Vaccine and Its Comparison With a Similar Formulation Produced From Plasma of COVID-19 Convalescent Donors. Front Med Technol 2021;3:772275.
   doi: 10.3389/fmedt.2021.772275pubmed: 35047966google scholar: lookup
9. He Y, Qu J, Wei L, Liao S, Zheng N, Liu Y, Wang X, Jing Y, Shen CK, Ji C, Luo G, Zhang Y, Xiang Q, Fu Y, Li S, Fan Y, Fang S, Wang P, Li L. Generation and Effect Testing of a SARS-CoV-2 RBD-Targeted Polyclonal Therapeutic Antibody Based on a 2-D Airway Organoid Screening System. Front Immunol 2021;12:689065.
   doi: 10.3389/fimmu.2021.689065pubmed: 34733269google scholar: lookup
10. Cunha LER, Stolet AA, Strauch MA, Pereira VAR, Dumard CH, Gomes AMO, Monteiro FL, Higa LM, Souza PNC, Fonseca JG, Pontes FE, Meirelles LGR, Albuquerque JWM, Sacramento CQ, Fintelman-Rodrigues N, Lima TM, Alvim RGF, Marsili FF, Caldeira MM, Zingali RB, de Oliveira GAP, Souza TML, Silva AS, Muller R, Rodrigues DDRF, Jesus da Costa L, Alves ADR, Pinto MA, Oliveira AC, Guedes HLM, Tanuri A, Castilho LR, Silva JL. Polyclonal F(ab')(2) fragments of equine antibodies raised against the spike protein neutralize SARS-CoV-2 variants with high potency. iScience 2021 Nov 19;24(11):103315.
    doi: 10.1016/j.isci.2021.103315pubmed: 34723156google scholar: lookup
11. Alape-Girón A, 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, Molina-Mora JA, Mora J, Narayanan A, Sanabria A, Sánchez A, Sánchez L, Segura Á, Segura E, Solano D, Soto C, Stynoski JL, Vargas M, Villalta M, Drexler JF, Gutiérrez JM. Heterologous Hyperimmune Polyclonal Antibodies Against SARS-CoV-2: A Broad Coverage, Affordable, and Scalable Potential Immunotherapy for COVID-19. Front Med (Lausanne) 2021;8:743325.
    doi: 10.3389/fmed.2021.743325pubmed: 34552950google scholar: lookup
12. 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 JA, Mora J, Sanabria A, Sánchez A, Sánchez L, Segura Á, Segura E, Solano D, Soto C, Stynoski JL, Vargas M, Villalta M, Reusken CBEM, Drosten C, Gutiérrez JM, Alape-Girón A, Drexler JF. High Efficacy of Therapeutic Equine Hyperimmune Antibodies Against SARS-CoV-2 Variants of Concern. Front Med (Lausanne) 2021;8:735853.
    doi: 10.3389/fmed.2021.735853pubmed: 34552949google scholar: lookup
13. Batista CM, Foti L. Anti-SARS-CoV-2 and anti-cytokine storm neutralizing antibody therapies against COVID-19: Update, challenges, and perspectives. Int Immunopharmacol 2021 Oct;99:108036.
    doi: 10.1016/j.intimp.2021.108036pubmed: 34371330google scholar: lookup
14. Majeed R, Bester J, Kgarosi K, Strydom M. Mapping Evidence on the Regulations Affecting the Accessibility, Availability, and Management of Snake Antivenom Globally: A Scoping Review. Trop Med Infect Dis 2025 Aug 14;10(8).
    doi: 10.3390/tropicalmed10080228pubmed: 40864131google scholar: lookup
15. Roncaglia-Pereira VA, Dumard CH, Monteiro-Machado M, Melo PA, Fonseca J, Meirelles L, Cunha-Ribeiro L, Souza P, da Silva JL, Castilho L, de Oliveira AC, Gomes AMO, Strauch MA. Long-Term Maintenance of High Neutralizing Anti-SARS-CoV-2 Antibodies Titres in Mares' Milk and Offspring Serum After Pregnant Mares Immunization With SARS-CoV-2 Spike Protein. Vet Med Sci 2025 Sep;11(5):e70488.
    doi: 10.1002/vms3.70488pubmed: 40699548google scholar: lookup
16. Arias-Arias JL, Monturiol-Gross L, Corrales-Aguilar E. A Live-Cell Imaging-Based Fluorescent SARS-CoV-2 Neutralization Assay by Antibody-Mediated Blockage of Receptor Binding Domain-ACE2 Interaction. BioTech (Basel) 2025 Feb 14;14(1).
    doi: 10.3390/biotech14010010pubmed: 39982277google scholar: lookup
17. Da Costa CBP, Cruz ACM, Penha JCQ, Castro HC, Da Cunha LER, Ratcliffe NA, Cisne R, Martins FJ. Using in vivo animal models for studying SARS-CoV-2. Expert Opin Drug Discov 2022 Feb;17(2):121-137.
    doi: 10.1080/17460441.2022.1995352pubmed: 34727803google scholar: lookup
18. Focosi D, Tuccori M, Franchini M. The Road towards Polyclonal Anti-SARS-CoV-2 Immunoglobulins (Hyperimmune Serum) for Passive Immunization in COVID-19. Life (Basel) 2021 Feb 15;11(2).
    doi: 10.3390/life11020144pubmed: 33671893google scholar: lookup