Carly Chisholm - Academia.edu (original) (raw)
Papers by Carly Chisholm
한국공업화학회 연구논문 초록집, 2016
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Journal of Pharmaceutical Sciences, 2020
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Subvisible particles in therapeutic protein products may act as adjuvants to provoke unwanted imm... more Subvisible particles in therapeutic protein products may act as adjuvants to provoke unwanted immune responses against administered proteins. Silicone oil is used as a lubricant in prefilled syringes, and microdroplets of silicone oil are frequently detected in protein formulations expelled from prefilled syringes. In this work, we investigated the potential of silicone oil microdroplets to act as an adjuvant to elicit immune responses against formulations containing foreign or self-protein in vivo . First, we tested the immunogenicity of formulations that contained a foreign protein and silicone oil microdroplets. A foreign model protein, ovalbumin (OVA), was added to emulsions of silicone oil microdroplets. Antibody responses in mice to subcutaneous injections of protein formulations that contained silicone oil microdroplets were measured using enzyme-linked immunosorbent assays. These responses were compared against responses to oil-free protein formulations and to protein formulations that contained microparticulate aluminum hydroxide (alum), the common vaccine adjuvant. When administered with silicone oil microdroplets, OVA formulations elicited robust anti-OVA IgG1 and IgG2a antibody responses in mice relative to oil-free OVA formulations. These responses were equivalent to those observed when alum microparticles were added to OVA formulations, indicating that silicone oil can act as a potent adjuvant against proteins containing foreign epitopes. Mice were also injected with similar formulations wherein recombinant murine growth hormone (rmGH), a recombinant self-protein, was substituted in place of OVA. In this study, we found that immunological tolerance was broken in mice when formulations of rmGH that contained silicone oil microdroplets were administered daily. Thus, silicone oil microdroplets can promote a breakage in immunological tolerance and induce antibody responses against recombinant self-proteins. Furthermore, we investigated the capacity of silicone oil microdroplets to induce antibody responses against a model protein known to form agglomerates and undergo structural perturbations in the presence of silicone oil microdroplets, hen egg lysozyme (HEL). Silicone oil microdroplets elicited robust antibody responses against HEL in non-transgenic mice where HEL was recognized as foreign, but silicone oil microdroplets did not promote a break in tolerance in immune tolerant transgenic mice. Thus, structural perturbations in proteins adsorbed to silicone oil microdroplets may not increase the immunogenicity of proteins.
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Journal of Pharmaceutical Sciences, Mar 1, 2020
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International Journal of Pharmaceutics, 2023
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International Journal of Pharmaceutics
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Proteins of pathogens whether prepared as inactivated viruses/bacteria or recombinantly produced ... more Proteins of pathogens whether prepared as inactivated viruses/bacteria or recombinantly produced can potentially act as vaccines. However, a recombinant protein alone is usually not immunogenic enough to evoke meaningful antibody production in human bodies, which leads to the formulation with a proper adjuvant. Currently, either aluminum hydroxide or aluminum phosphate is used in the most of adjuvanted vaccines in the market. Considering that the both aluminum salts are prone to aggregation upon freeze in the cold chain, the vaccine formulations with aluminum salts can be greatly stabilized in the absence of water. Since proteins in general become more stable upon heat shocks as well when they are in a solid state drying approaches in vaccine formulation can also be justified. As a part of continued efforts to prove the concept, here we report the stabilization and characterization of Ebola glycoprotein adjuvanted with aluminum hydroxide by lyophilization.
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Subvisible particles in therapeutic protein products may act as adjuvants to provoke unwanted imm... more Subvisible particles in therapeutic protein products may act as adjuvants to provoke unwanted immune responses against administered proteins. Silicone oil is used as a lubricant in prefilled syringes, and microdroplets of silicone oil are frequently detected in protein formulations expelled from prefilled syringes. In this work, we investigated the potential of silicone oil microdroplets to act as an adjuvant to elicit immune responses against formulations containing foreign or self-protein in vivo . First, we tested the immunogenicity of formulations that contained a foreign protein and silicone oil microdroplets. A foreign model protein, ovalbumin (OVA), was added to emulsions of silicone oil microdroplets. Antibody responses in mice to subcutaneous injections of protein formulations that contained silicone oil microdroplets were measured using enzyme-linked immunosorbent assays. These responses were compared against responses to oil-free protein formulations and to protein formul...
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Journal of Pharmaceutical Sciences, 2019
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Journal of Pharmaceutical Sciences, 2019
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European Journal of Pharmaceutics and Biopharmaceutics, 2019
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Journal of pharmaceutical sciences, Jun 16, 2017
Silicone oil microdroplets may act as adjuvants, promoting unwanted immune responses against both... more Silicone oil microdroplets may act as adjuvants, promoting unwanted immune responses against both foreign and self-proteins. Proteins often unfold upon adsorption to silicone oil microdroplets, but it is unclear how such unfolding might affect the immune response. In this study, we found that hen egg lysozyme (HEL) readily adsorbed to silicone oil microdroplets and perturbed the conformation of HEL. We compared the immune response to injections of HEL formulated in the presence and absence of silicone oil microdroplets in both wild-type mice and transgenic littermates that express a soluble form of HEL (sHEL), thus rendering them immunologically tolerant to this nominal self-antigen. Following two subcutaneous injections of a HEL formulation containing silicone oil microdroplets, wild-type mice exhibited a stronger IgG1 antibody response against HEL compared to the response in wild-type mice administered an oil-free HEL formulation. However, when HEL was subcutaneously administered ...
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Journal of pharmaceutical sciences, May 25, 2016
Therapeutic protein products can cause adverse immune responses in patients. The presence of subv... more 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...
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Journal of pharmaceutical sciences, Jan 17, 2015
Subvisible particles in a therapeutic protein product may act as adjuvants to promote unwanted im... more 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 sili...
Bookmarks Related papers MentionsView impact
Journal of pharmaceutical sciences, Jan 17, 2015
Subvisible particles in a therapeutic protein product may act as adjuvants to promote unwanted im... more 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 sili...
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한국공업화학회 연구논문 초록집, 2016
Bookmarks Related papers MentionsView impact
Journal of Pharmaceutical Sciences, 2020
Bookmarks Related papers MentionsView impact
Subvisible particles in therapeutic protein products may act as adjuvants to provoke unwanted imm... more Subvisible particles in therapeutic protein products may act as adjuvants to provoke unwanted immune responses against administered proteins. Silicone oil is used as a lubricant in prefilled syringes, and microdroplets of silicone oil are frequently detected in protein formulations expelled from prefilled syringes. In this work, we investigated the potential of silicone oil microdroplets to act as an adjuvant to elicit immune responses against formulations containing foreign or self-protein in vivo . First, we tested the immunogenicity of formulations that contained a foreign protein and silicone oil microdroplets. A foreign model protein, ovalbumin (OVA), was added to emulsions of silicone oil microdroplets. Antibody responses in mice to subcutaneous injections of protein formulations that contained silicone oil microdroplets were measured using enzyme-linked immunosorbent assays. These responses were compared against responses to oil-free protein formulations and to protein formulations that contained microparticulate aluminum hydroxide (alum), the common vaccine adjuvant. When administered with silicone oil microdroplets, OVA formulations elicited robust anti-OVA IgG1 and IgG2a antibody responses in mice relative to oil-free OVA formulations. These responses were equivalent to those observed when alum microparticles were added to OVA formulations, indicating that silicone oil can act as a potent adjuvant against proteins containing foreign epitopes. Mice were also injected with similar formulations wherein recombinant murine growth hormone (rmGH), a recombinant self-protein, was substituted in place of OVA. In this study, we found that immunological tolerance was broken in mice when formulations of rmGH that contained silicone oil microdroplets were administered daily. Thus, silicone oil microdroplets can promote a breakage in immunological tolerance and induce antibody responses against recombinant self-proteins. Furthermore, we investigated the capacity of silicone oil microdroplets to induce antibody responses against a model protein known to form agglomerates and undergo structural perturbations in the presence of silicone oil microdroplets, hen egg lysozyme (HEL). Silicone oil microdroplets elicited robust antibody responses against HEL in non-transgenic mice where HEL was recognized as foreign, but silicone oil microdroplets did not promote a break in tolerance in immune tolerant transgenic mice. Thus, structural perturbations in proteins adsorbed to silicone oil microdroplets may not increase the immunogenicity of proteins.
Bookmarks Related papers MentionsView impact
Journal of Pharmaceutical Sciences, Mar 1, 2020
Bookmarks Related papers MentionsView impact
International Journal of Pharmaceutics, 2023
Bookmarks Related papers MentionsView impact
International Journal of Pharmaceutics
Bookmarks Related papers MentionsView impact
Proteins of pathogens whether prepared as inactivated viruses/bacteria or recombinantly produced ... more Proteins of pathogens whether prepared as inactivated viruses/bacteria or recombinantly produced can potentially act as vaccines. However, a recombinant protein alone is usually not immunogenic enough to evoke meaningful antibody production in human bodies, which leads to the formulation with a proper adjuvant. Currently, either aluminum hydroxide or aluminum phosphate is used in the most of adjuvanted vaccines in the market. Considering that the both aluminum salts are prone to aggregation upon freeze in the cold chain, the vaccine formulations with aluminum salts can be greatly stabilized in the absence of water. Since proteins in general become more stable upon heat shocks as well when they are in a solid state drying approaches in vaccine formulation can also be justified. As a part of continued efforts to prove the concept, here we report the stabilization and characterization of Ebola glycoprotein adjuvanted with aluminum hydroxide by lyophilization.
Bookmarks Related papers MentionsView impact
Subvisible particles in therapeutic protein products may act as adjuvants to provoke unwanted imm... more Subvisible particles in therapeutic protein products may act as adjuvants to provoke unwanted immune responses against administered proteins. Silicone oil is used as a lubricant in prefilled syringes, and microdroplets of silicone oil are frequently detected in protein formulations expelled from prefilled syringes. In this work, we investigated the potential of silicone oil microdroplets to act as an adjuvant to elicit immune responses against formulations containing foreign or self-protein in vivo . First, we tested the immunogenicity of formulations that contained a foreign protein and silicone oil microdroplets. A foreign model protein, ovalbumin (OVA), was added to emulsions of silicone oil microdroplets. Antibody responses in mice to subcutaneous injections of protein formulations that contained silicone oil microdroplets were measured using enzyme-linked immunosorbent assays. These responses were compared against responses to oil-free protein formulations and to protein formul...
Bookmarks Related papers MentionsView impact
Journal of Pharmaceutical Sciences, 2019
Bookmarks Related papers MentionsView impact
Journal of Pharmaceutical Sciences, 2019
Bookmarks Related papers MentionsView impact
European Journal of Pharmaceutics and Biopharmaceutics, 2019
Bookmarks Related papers MentionsView impact
Journal of pharmaceutical sciences, Jun 16, 2017
Silicone oil microdroplets may act as adjuvants, promoting unwanted immune responses against both... more Silicone oil microdroplets may act as adjuvants, promoting unwanted immune responses against both foreign and self-proteins. Proteins often unfold upon adsorption to silicone oil microdroplets, but it is unclear how such unfolding might affect the immune response. In this study, we found that hen egg lysozyme (HEL) readily adsorbed to silicone oil microdroplets and perturbed the conformation of HEL. We compared the immune response to injections of HEL formulated in the presence and absence of silicone oil microdroplets in both wild-type mice and transgenic littermates that express a soluble form of HEL (sHEL), thus rendering them immunologically tolerant to this nominal self-antigen. Following two subcutaneous injections of a HEL formulation containing silicone oil microdroplets, wild-type mice exhibited a stronger IgG1 antibody response against HEL compared to the response in wild-type mice administered an oil-free HEL formulation. However, when HEL was subcutaneously administered ...
Bookmarks Related papers MentionsView impact
Journal of pharmaceutical sciences, May 25, 2016
Therapeutic protein products can cause adverse immune responses in patients. The presence of subv... more 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...
Bookmarks Related papers MentionsView impact
Journal of pharmaceutical sciences, Jan 17, 2015
Subvisible particles in a therapeutic protein product may act as adjuvants to promote unwanted im... more 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 sili...
Bookmarks Related papers MentionsView impact
Journal of pharmaceutical sciences, Jan 17, 2015
Subvisible particles in a therapeutic protein product may act as adjuvants to promote unwanted im... more 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 sili...
Bookmarks Related papers MentionsView impact