In Vivo Analysis of the Potency of Silicone Oil Microdroplets as Immunological Adjuvants in Protein Formulations
Open accessAbstract
Subvisible particles in a therapeutic protein product may act as adjuvants to promote unwanted immune responses against the protein. Silicone oil is used as a lubricant in prefilled syringes, and microdroplets of silicone oil are often detected in protein formulations expelled from prefilled syringes. In order to test the adjuvant potency of silicone oil microdroplets, antibody responses in mice to subcutaneous injections of formulations of ovalbumin (OVA) that contained silicone oil microdroplets were measured. These responses were compared against responses to oil-free OVA formulations and to OVA formulations that contained microparticulate aluminum hydroxide ("alum"), the common vaccine adjuvant. When administered with high concentrations of silicone oil microdroplets, OVA formulations elicited strong anti-OVA IgG1 and IgG2a antibody responses. These responses were equivalent to those observed when alum microparticles were added to OVA formulations, suggesting that silicone oil can act as a potent adjuvant. However, when OVA formulations were prepared with lower levels of silicone oil that had been obtained directly from commercial siliconized syringes, the anti-OVA antibody response was not enhanced significantly compared with responses against OVA alone.
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Processes that result in SO-protein complex formation and protein aggregates can elicit an immune response.
“All of these processes that result in SO-protein complex formation as well as protein aggregates can, in turn, elicit an immune response [61, 69].”
From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [69]
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- Authors
- Chisholm, C. F., Nguyen, B. H., Soucie, K. R., Torres, R. M., Carpenter, J. F., & Randolph, T. W.
- Affiliations
- University of Colorado Boulder (US)
- University of Colorado Anschutz (US)
- Corresponding author
- Randolph, Theodore W.
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2015-11
- Volume
- 104
- Issue
- 11
- Pages
- 3681-3690
- ISSN
- 0022-3549 (ISSN-L)
- PMC
- PMC4604024
- OpenAlex
- W1757210261
- Cited by
- 55
- References
- 57
- Citations by year
- 2026: 2 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 9 · 2020: 10 · 2019: 9 · 2017: 4 · 2016: 4 · 2015: 1
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Pharmaceutical Sciences (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- NIH (ROI EB006006)
- FDA Office of Women’s Health
- US Food and Drug Administration
- Oak Ridge Institute for Science and Education
- US Department of Energy
- FDA/Center
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- immunoadjuvant, prefilled syringes, subvisible particles, therapeutic protein formulations, ovalbumin, aluminum hydroxide, antibody response, IgG1, IgG2a
- MeSH terms
- Adjuvants, Immunologic, Aluminum Hydroxide, Animals, Antibody Formation, Immunoglobulin G, Mice, Inbred BALB C, Mice, Inbred C57BL, Ovalbumin, Silicone Oils, Syringes, Mice
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