Guinea Pig Animal Model for Predicting Immunogenicity of Insulin Analogues
Keywords:
Neutralizing Nab, Lispro, Glargine, Aspart, AIA, and HRP Conjugated Secondary Antibody
Abstract
Our objective is to use the guinea pig model to evaluate the immunogenicity of recombinant insulin and three specific insulin analogs: Glargine, Aspart, and Lispro. These analogs have been structurally modified from the original insulin sequence to enhance their pharmacokinetic and pharmacodynamic properties, leading to better blood glucose management in diabetic patients. This study aims to determine whether these commercially available analogs can trigger an immune response, potentially leading to the production of antibodies. Such immune responses could reduce the effectiveness of the insulin analogs and cause adverse effects. Additionally, we aim to gain valuable insights into the immunogenicity of these insulin analogs, thereby enhancing our understanding of their safety and efficacy. This knowledge will support the development of improved insulin therapies for diabetes management.
References
1. Home P, Derwahl KM, Ziemen M, et al. Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes. 2018;20(2):160-170. doi:10.1089/dia.2017.0373
2. Cheng R, Taleb N, Stainforth-Dubois M, Rabasa-Lhoret R. The promising future of insulin therapy in diabetes mellitus. Am J Physiol - Endocrinol Metab. 2021;320(5):E886-E890. doi:10.1152/AJPENDO.00608.2020
3. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133-2223. doi:10.1152/physrev.00063.2017
4. Ae SO, Thi TH, Ae P, et al. Animal insulin therapy induces a biased insulin antibody response that persists for years after introduction of human insulin. doi:10.1007/s00592-009-0135-2
5. Jarosinski MA, Dhayalan B, Chen YS, Chatterjee D, Varas N, Weiss MA. Structural principles of insulin formulation and analog design: A century of innovation. Mol Metab. 2021;52(August):1-19. doi:10.1016/j.molmet.2021.101325
6. Menting JG, Whittaker J, Margetts MB, et al. How insulin engages its primary binding site on the insulin receptor. Nature. Published online 2013. doi:10.1038/nature11781
7. Heise T, Mathieu C. Impact of the mode of protraction of basal insulin therapies on their pharmacokinetic and pharmacodynamic properties and resulting clinical outcomes. Diabetes, Obes Metab. 2017;19(1). doi:10.1111/dom.12782
8. Zieliński M, Romanik-Chruścielewska A, Mikiewicz D, et al. Expression and purification of recombinant human insulin from E. coli 20 strain. Protein Expr Purif. 2019;157:63-69. doi:10.1016/j.pep.2019.02.002
9. Makulu DR, Wright P. Immune response to insulin in guinea pigs. Metabolism. 1971;20(8):770-781. doi:10.1016/S0026-0495(71)80007-0
10. Fineberg SE, Kawabata TT, Finco-Kent D, Fountaine RJ, Finch GL, Krasner AS. Immunological responses to exogenous insulin. Endocr Rev. 2007;28(6):625-652. doi:10.1210/er.2007-0002
11. Home P, Derwahl KM, Ziemen M, et al. Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes. Diabetes Technol Ther. 2018;20(2):160-170. doi:10.1089/dia.2017.0373
12. GARG SK, WERNICKE-PANTEN K, WARDECKI M, et al. 129-LB: Similar Efficacy, Safety, and Immunogenicity in People with Diabetes Using SAR341402 or Insulin Aspart: Gemelli 1 Study. Diabetes. 2019;68(Supplement 1). doi:10.2337/db19-129-lb
13. Ilag LL, Deeg MA, Costigan T, et al. Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus. Diabetes, Obes Metab. 2016;18(2):159-168. doi:10.1111/dom.12584
14. Varadarajan S, Muruganandam A, Kumar VR. Development and Characterization of Guinea Pig Anti-Insulin Polyclonal Antibody. Appl Biochem Biotechnol. Published online September 15, 2023. doi:10.1007/s12010-023-04670-z
15. Fineberg SE, Galloway JA, Fineberg NS, Rathbun MJ, Hufferd S. Immunogenicity of recombinant DNA human insulin. Diabetologia. 1983;25(6):465-469. doi:10.1007/BF00284452
16. Fishman JB, Berg EA. Peptide affinity purification of antibodies. Cold Spring Harb Protoc. 2019;2019(5):379-381. doi:10.1101/pdb.prot099176
17. Jaeger C, Winter S, Eckhard M, Hardt P, Brendel MD, Bretzel RG. Binding characteristics and crossreactivity of insulin autoantibodies and insulin antibodies directed to three different insulin molecules. Acta Diabetol. 2008;45(3):191-194. doi:10.1007/s00592-008-0041-z
18. Heinemann L, Owens D. Biosimilar Insulin and Insulin Antibodies. Vol 7.; 2013. www.journalofdst.org
19. Wilkin T, Nicholson S, Casey C. A micro enzyme-linked immunosorbent assay for insulin antibodies in serum. J Immunol Methods. 1985;76(1):185-194. doi:10.1016/0022-1759(85)90490-9
20. Cheng LT, Zeng YJ, Chu CY, Wang HY. Development of a quick dot blot assay for the titering of bovine ephemeral fever virus. BMC Vet Res. 2019;15(1). doi:10.1186/s12917-019-2059-6
2. Cheng R, Taleb N, Stainforth-Dubois M, Rabasa-Lhoret R. The promising future of insulin therapy in diabetes mellitus. Am J Physiol - Endocrinol Metab. 2021;320(5):E886-E890. doi:10.1152/AJPENDO.00608.2020
3. Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4):2133-2223. doi:10.1152/physrev.00063.2017
4. Ae SO, Thi TH, Ae P, et al. Animal insulin therapy induces a biased insulin antibody response that persists for years after introduction of human insulin. doi:10.1007/s00592-009-0135-2
5. Jarosinski MA, Dhayalan B, Chen YS, Chatterjee D, Varas N, Weiss MA. Structural principles of insulin formulation and analog design: A century of innovation. Mol Metab. 2021;52(August):1-19. doi:10.1016/j.molmet.2021.101325
6. Menting JG, Whittaker J, Margetts MB, et al. How insulin engages its primary binding site on the insulin receptor. Nature. Published online 2013. doi:10.1038/nature11781
7. Heise T, Mathieu C. Impact of the mode of protraction of basal insulin therapies on their pharmacokinetic and pharmacodynamic properties and resulting clinical outcomes. Diabetes, Obes Metab. 2017;19(1). doi:10.1111/dom.12782
8. Zieliński M, Romanik-Chruścielewska A, Mikiewicz D, et al. Expression and purification of recombinant human insulin from E. coli 20 strain. Protein Expr Purif. 2019;157:63-69. doi:10.1016/j.pep.2019.02.002
9. Makulu DR, Wright P. Immune response to insulin in guinea pigs. Metabolism. 1971;20(8):770-781. doi:10.1016/S0026-0495(71)80007-0
10. Fineberg SE, Kawabata TT, Finco-Kent D, Fountaine RJ, Finch GL, Krasner AS. Immunological responses to exogenous insulin. Endocr Rev. 2007;28(6):625-652. doi:10.1210/er.2007-0002
11. Home P, Derwahl KM, Ziemen M, et al. Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes. Diabetes Technol Ther. 2018;20(2):160-170. doi:10.1089/dia.2017.0373
12. GARG SK, WERNICKE-PANTEN K, WARDECKI M, et al. 129-LB: Similar Efficacy, Safety, and Immunogenicity in People with Diabetes Using SAR341402 or Insulin Aspart: Gemelli 1 Study. Diabetes. 2019;68(Supplement 1). doi:10.2337/db19-129-lb
13. Ilag LL, Deeg MA, Costigan T, et al. Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus. Diabetes, Obes Metab. 2016;18(2):159-168. doi:10.1111/dom.12584
14. Varadarajan S, Muruganandam A, Kumar VR. Development and Characterization of Guinea Pig Anti-Insulin Polyclonal Antibody. Appl Biochem Biotechnol. Published online September 15, 2023. doi:10.1007/s12010-023-04670-z
15. Fineberg SE, Galloway JA, Fineberg NS, Rathbun MJ, Hufferd S. Immunogenicity of recombinant DNA human insulin. Diabetologia. 1983;25(6):465-469. doi:10.1007/BF00284452
16. Fishman JB, Berg EA. Peptide affinity purification of antibodies. Cold Spring Harb Protoc. 2019;2019(5):379-381. doi:10.1101/pdb.prot099176
17. Jaeger C, Winter S, Eckhard M, Hardt P, Brendel MD, Bretzel RG. Binding characteristics and crossreactivity of insulin autoantibodies and insulin antibodies directed to three different insulin molecules. Acta Diabetol. 2008;45(3):191-194. doi:10.1007/s00592-008-0041-z
18. Heinemann L, Owens D. Biosimilar Insulin and Insulin Antibodies. Vol 7.; 2013. www.journalofdst.org
19. Wilkin T, Nicholson S, Casey C. A micro enzyme-linked immunosorbent assay for insulin antibodies in serum. J Immunol Methods. 1985;76(1):185-194. doi:10.1016/0022-1759(85)90490-9
20. Cheng LT, Zeng YJ, Chu CY, Wang HY. Development of a quick dot blot assay for the titering of bovine ephemeral fever virus. BMC Vet Res. 2019;15(1). doi:10.1186/s12917-019-2059-6
Published
2024-06-15
How to Cite
Varadarajan Sathiya, & V Ramesh Kumar. (2024). Guinea Pig Animal Model for Predicting Immunogenicity of Insulin Analogues. Revista Electronica De Veterinaria, 25(1), 632-642. https://doi.org/10.53555/redvet.v25i1.622
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