TY - JOUR
T1 - Transferon™, a peptide mixture with immunomodulatory properties is not immunogenic when administered with various adjuvants
AU - Avila, Sandra
AU - Muñoz-García, Leslie
AU - Vázquez-Leyva, Said
AU - Salinas-Jazmín, Nohemí
AU - Medina-Rivero, Emilio
AU - Pavón, Lenin
AU - Mellado-Sánchez, Gabriela
AU - Chacón-Salinas, Rommel
AU - Estrada-Parra, Sergio
AU - Vallejo-Castillo, Luis
AU - Pérez-Tapia, Sonia Mayra
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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 peptidederived 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 lg 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.
AB - 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 peptidederived 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 lg 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.
KW - ADA
KW - Adjuvants
KW - Immunogenicity
KW - Transferon™
KW - hDLE
UR - http://www.scopus.com/inward/record.url?scp=85046052210&partnerID=8YFLogxK
U2 - 10.1080/1547691X.2017.1346009
DO - 10.1080/1547691X.2017.1346009
M3 - Artículo
SN - 1547-691X
VL - 14
SP - 169
EP - 177
JO - Journal of Immunotoxicology
JF - Journal of Immunotoxicology
IS - 1
ER -