title: Silicone Oil Microdroplets Can Induce Antibody Responses Against Recombinant Murine Growth Hormone in Mice.
abstract: Therapeutic protein products can cause adverse immune responses in patients. The presence of subvisible particles is a potential contributing factor to the immunogenicity of parenterally administered therapeutic protein formulations. Silicone oil microdroplets, which derive from silicone oil used as a lubricating coating on barrels of prefilled glass syringes, are often found in formulations. In this study, we investigated the potential of silicone oil microdroplets to act as adjuvants to induce an immune response in mice against a recombinant murine protein. Antibody responses in mice to subcutaneous injections of formulations of recombinant murine growth hormone (rmGH) that contained silicone oil microdroplets were measured and compared to responses to oil-free rmGH formulations. When rmGH formulations containing silicone oil microdroplets were administered once every other week, anti-rmGH antibodies were not detected. In contrast, mice exhibited a small IgG1 response against rmGH when silicone oil-containing rmGH formulations were administered daily, and an anti-rmGH IgM response was observed at later time points. Our findings showed that silicone oil microdroplets can act as an adjuvant to promote a break in immunological tolerance and induce antibody responses against a recombinant self-protein.
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309.
authors.forename: Carly Fleagle
authors.initials: CF
authors.lastname: Chisholm
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309.
authors.forename: Abby E
authors.initials: AE
authors.lastname: Baker
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309.
authors.forename: Kaitlin R
authors.initials: KR
authors.lastname: Soucie
authors.affiliation: Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, Colorado 80045.
authors.forename: Raul M
authors.initials: RM
authors.lastname: Torres
authors.affiliation: Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045.
authors.forename: John F
authors.initials: JF
authors.lastname: Carpenter
authors.affiliation: Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 80309. Electronic address: Theodore.randolph@colorado.edu.
authors.forename: Theodore W
authors.initials: TW
authors.lastname: Randolph
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000276:immunology*; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008863:Microspheres; D010316:Particle Size; D012827:Silicone Oils / Q000008:administration & dosage*
chemical_list: D012827:Silicone Oils; D013006:Growth Hormone
keywords: adjuvant effect; immune response; immunogenicity; particle size; prefilled syringes; protein aggregation; protein formulation; protein structure; silicone oil; subvisible particles