Sandra Avila, Leslie Muñoz-García, Said Vázquez-Leyva, Nohemí Salinas-Jazmín, Emilio Medina-Rivero, Lenin Pavón, Gabriela Mellado-Sánchez, Rommel Chacón-Salinas, Sergio Estrada-Parra, Luis Vallejo-Castillo, Sonia Mayra Pérez-Tapia
{"title":"Transferon™是一种具有免疫调节特性的多肽混合物,当与各种佐剂一起使用时,不会产生免疫原性。","authors":"Sandra Avila, Leslie Muñoz-García, Said Vázquez-Leyva, Nohemí Salinas-Jazmín, Emilio Medina-Rivero, Lenin Pavón, Gabriela Mellado-Sánchez, Rommel Chacón-Salinas, Sergio Estrada-Parra, Luis Vallejo-Castillo, Sonia Mayra Pérez-Tapia","doi":"10.1080/1547691X.2017.1346009","DOIUrl":null,"url":null,"abstract":"<p><p>Transferon, a human dialyzable leukocyte extract (hDLE), is a biotherapeutic that comprises a complex mixture of low-molecular-weight peptides (< 10 kDa) and is used to treat diseases with an inflammatory component. Some biotherapeutics, including those composed of peptides, can induce anti-drug antibodies (ADA) that block or diminish their therapeutic effect. Nevertheless, few studies have evaluated peptide-derived drug immunogenicity. In this study, the immunogenicity of Transferon was examined in a murine model during an immunization scheme using the following adjuvants: Al(OH)<sub>3</sub>, incomplete Freund's adjuvant (IFA), or Titermax Gold. The inoculation scheme entailed three routes of administration (intraperitoneal, Day 1; subcutaneous, Day 7; and intramuscular, Day 14) using 200 μg Transferon/inoculation. Serum samples were collected on Day 21. Total IgG levels were quantitated by affinity chromatography, and specific antibodies against components of Transferon were analyzed by dot-blot and ELISA. Ovalbumin (OVA, 44 kDa) and peptides from hydrolyzed collagen (PFHC, < 17 kDa) were used as positive and negative controls, respectively, in the same inoculation scheme and analyses for Transferon. OVA, PFHC, and Transferon increased total IgG concentrations in mice. However, only IgG antibodies against OVA were detected. Based on the results, it is concluded that Transferon does not induce generation of specific antibodies against its components in this model, regardless of adjuvant and route of administration. These results support the safety of Transferon by confirming its inability to induce ADA in this animal model.</p>","PeriodicalId":16073,"journal":{"name":"Journal of Immunotoxicology","volume":"14 1","pages":"169-177"},"PeriodicalIF":2.4000,"publicationDate":"2017-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/1547691X.2017.1346009","citationCount":"3","resultStr":"{\"title\":\"Transferon™, a peptide mixture with immunomodulatory properties is not immunogenic when administered with various adjuvants.\",\"authors\":\"Sandra Avila, Leslie Muñoz-García, Said Vázquez-Leyva, Nohemí Salinas-Jazmín, Emilio Medina-Rivero, Lenin Pavón, Gabriela Mellado-Sánchez, Rommel Chacón-Salinas, Sergio Estrada-Parra, Luis Vallejo-Castillo, Sonia Mayra Pérez-Tapia\",\"doi\":\"10.1080/1547691X.2017.1346009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Transferon, a human dialyzable leukocyte extract (hDLE), is a biotherapeutic that comprises a complex mixture of low-molecular-weight peptides (< 10 kDa) and is used to treat diseases with an inflammatory component. Some biotherapeutics, including those composed of peptides, can induce anti-drug antibodies (ADA) that block or diminish their therapeutic effect. Nevertheless, few studies have evaluated peptide-derived drug immunogenicity. In this study, the immunogenicity of Transferon was examined in a murine model during an immunization scheme using the following adjuvants: Al(OH)<sub>3</sub>, incomplete Freund's adjuvant (IFA), or Titermax Gold. The inoculation scheme entailed three routes of administration (intraperitoneal, Day 1; subcutaneous, Day 7; and intramuscular, Day 14) using 200 μg Transferon/inoculation. Serum samples were collected on Day 21. Total IgG levels were quantitated by affinity chromatography, and specific antibodies against components of Transferon were analyzed by dot-blot and ELISA. Ovalbumin (OVA, 44 kDa) and peptides from hydrolyzed collagen (PFHC, < 17 kDa) were used as positive and negative controls, respectively, in the same inoculation scheme and analyses for Transferon. OVA, PFHC, and Transferon increased total IgG concentrations in mice. However, only IgG antibodies against OVA were detected. Based on the results, it is concluded that Transferon does not induce generation of specific antibodies against its components in this model, regardless of adjuvant and route of administration. These results support the safety of Transferon by confirming its inability to induce ADA in this animal model.</p>\",\"PeriodicalId\":16073,\"journal\":{\"name\":\"Journal of Immunotoxicology\",\"volume\":\"14 1\",\"pages\":\"169-177\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2017-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1080/1547691X.2017.1346009\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Immunotoxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/1547691X.2017.1346009\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Immunotoxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1547691X.2017.1346009","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
Transferon™, a peptide mixture with immunomodulatory properties is not immunogenic when administered with various adjuvants.
Transferon, a human dialyzable leukocyte extract (hDLE), is a biotherapeutic that comprises a complex mixture of low-molecular-weight peptides (< 10 kDa) and is used to treat diseases with an inflammatory component. Some biotherapeutics, including those composed of peptides, can induce anti-drug antibodies (ADA) that block or diminish their therapeutic effect. Nevertheless, few studies have evaluated peptide-derived drug immunogenicity. In this study, the immunogenicity of Transferon was examined in a murine model during an immunization scheme using the following adjuvants: Al(OH)3, incomplete Freund's adjuvant (IFA), or Titermax Gold. The inoculation scheme entailed three routes of administration (intraperitoneal, Day 1; subcutaneous, Day 7; and intramuscular, Day 14) using 200 μg Transferon/inoculation. Serum samples were collected on Day 21. Total IgG levels were quantitated by affinity chromatography, and specific antibodies against components of Transferon were analyzed by dot-blot and ELISA. Ovalbumin (OVA, 44 kDa) and peptides from hydrolyzed collagen (PFHC, < 17 kDa) were used as positive and negative controls, respectively, in the same inoculation scheme and analyses for Transferon. OVA, PFHC, and Transferon increased total IgG concentrations in mice. However, only IgG antibodies against OVA were detected. Based on the results, it is concluded that Transferon does not induce generation of specific antibodies against its components in this model, regardless of adjuvant and route of administration. These results support the safety of Transferon by confirming its inability to induce ADA in this animal model.
期刊介绍:
The Journal of Immunotoxicology is an open access, peer-reviewed journal that provides a needed singular forum for the international community of immunotoxicologists, immunologists, and toxicologists working in academia, government, consulting, and industry to both publish their original research and be made aware of the research findings of their colleagues in a timely manner. Research from many subdisciplines are presented in the journal, including the areas of molecular, developmental, pulmonary, regulatory, nutritional, mechanistic, wildlife, and environmental immunotoxicology, immunology, and toxicology. Original research articles as well as timely comprehensive reviews are published.