Immunogenicity of Recombinant Human Interferon Beta Interacting with Particles of Glass, Metal, and Polystyrene
Aggregates play a major role in the immunogenicity of recombinant human interferon beta (rhIFNβ), a protein used to treat multiple sclerosis. A possible cause of aggregation is interaction between therapeutic protein and surfaces encountered during processing, storage, and administration. Moreover,...
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| Veröffentlicht in: | Journal of pharmaceutical sciences 2012-01, Vol.101 (1), p.187-199 |
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| creator | Van Beers, Miranda M.C. Gilli, Francesca Schellekens, Huub Randolph, Theodore W. Jiskoot, Wim |
| description | Aggregates play a major role in the immunogenicity of recombinant human interferon beta (rhIFNβ), a protein used to treat multiple sclerosis. A possible cause of aggregation is interaction between therapeutic protein and surfaces encountered during processing, storage, and administration. Moreover, proteins may adsorb to particles shed from these surfaces. In this work, we studied the immunogenicity of recombinant human interferon beta-1a (rhIFNβ-1a) interacting with glass microparticles, stainless steel microparticles, and polystyrene nanoparticles. At physiological pH, rhIFNβ-1a readily adsorbed to the particles, while the degree of adsorption was influenced by the ionic strength of the phosphate buffer. Front-face fluorescence showed that the tertiary structure of rhIFNβ-1a slightly changed upon adsorption to glass. The interaction with stainless steel microparticles resulted in increased levels of aggregates in the free protein fraction. Furthermore, protein adsorbed to stainless steel microparticles was more difficult to desorb than protein adsorbed to glass. Incubation with stainless steel considerably enhanced the immunogenicity of rhIFNβ-1a in transgenic mice immune tolerant for human interferon beta. The protein fraction adsorbed on stainless steel particles was responsible for this. In conclusion, rhIFNβ-1a adsorbs to common hydrophilic surface materials, possibly increasing the immunogenicity of the protein. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association. |
| doi_str_mv | 10.1002/jps.22744 |
| format | Article |
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A possible cause of aggregation is interaction between therapeutic protein and surfaces encountered during processing, storage, and administration. Moreover, proteins may adsorb to particles shed from these surfaces. In this work, we studied the immunogenicity of recombinant human interferon beta-1a (rhIFNβ-1a) interacting with glass microparticles, stainless steel microparticles, and polystyrene nanoparticles. At physiological pH, rhIFNβ-1a readily adsorbed to the particles, while the degree of adsorption was influenced by the ionic strength of the phosphate buffer. Front-face fluorescence showed that the tertiary structure of rhIFNβ-1a slightly changed upon adsorption to glass. The interaction with stainless steel microparticles resulted in increased levels of aggregates in the free protein fraction. Furthermore, protein adsorbed to stainless steel microparticles was more difficult to desorb than protein adsorbed to glass. Incubation with stainless steel considerably enhanced the immunogenicity of rhIFNβ-1a in transgenic mice immune tolerant for human interferon beta. The protein fraction adsorbed on stainless steel particles was responsible for this. In conclusion, rhIFNβ-1a adsorbs to common hydrophilic surface materials, possibly increasing the immunogenicity of the protein. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.</description><identifier>ISSN: 0022-3549</identifier><identifier>ISSN: 1520-6017</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1002/jps.22744</identifier><identifier>PMID: 21918983</identifier><identifier>CODEN: JPMSAE</identifier><language>eng</language><publisher>Hoboken: Elsevier Inc</publisher><subject>Adsorption ; alpha -Interferon ; Animals ; beta -Interferon ; Biological and medical sciences ; Buffers ; Chromium ; Fluorescence ; fluorescence spectroscopy ; General pharmacology ; Glass - chemistry ; Humans ; Hydrogen-Ion Concentration ; Immune Tolerance ; Immunogenicity ; Interferon ; Interferon beta-1a ; Interferon-beta - chemistry ; Interferon-beta - immunology ; Ionic strength ; Medical sciences ; Metals ; Metals - chemistry ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; microparticles ; Multiple sclerosis ; nanoparticles ; Nanoparticles - chemistry ; Osmolar Concentration ; pH effects ; Pharmaceutical technology. Pharmaceutical industry ; Pharmacology. Drug treatments ; Phosphate ; polystyrene ; Polystyrenes - chemistry ; protein aggregates ; Protein structure ; Protein Structure, Tertiary ; recombinant human interferon beta ; Recombinant Proteins - chemistry ; Recombinant Proteins - immunology ; stainless steel ; Surface Properties ; Tertiary structure ; Transgenic mice ; transgenics</subject><ispartof>Journal of pharmaceutical sciences, 2012-01, Vol.101 (1), p.187-199</ispartof><rights>2012 Wiley-Liss, Inc.</rights><rights>Copyright © 2011 Wiley‐Liss, Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4974-31504cdfa39d417545a8e79db96f4b96cc1cb9e43aa3bfb3b2ad7224cf88e4cf3</citedby><cites>FETCH-LOGICAL-c4974-31504cdfa39d417545a8e79db96f4b96cc1cb9e43aa3bfb3b2ad7224cf88e4cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjps.22744$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjps.22744$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,4021,27921,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25505704$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21918983$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van Beers, Miranda M.C.</creatorcontrib><creatorcontrib>Gilli, Francesca</creatorcontrib><creatorcontrib>Schellekens, Huub</creatorcontrib><creatorcontrib>Randolph, Theodore W.</creatorcontrib><creatorcontrib>Jiskoot, Wim</creatorcontrib><title>Immunogenicity of Recombinant Human Interferon Beta Interacting with Particles of Glass, Metal, and Polystyrene</title><title>Journal of pharmaceutical sciences</title><addtitle>J. Pharm. Sci</addtitle><description>Aggregates play a major role in the immunogenicity of recombinant human interferon beta (rhIFNβ), a protein used to treat multiple sclerosis. A possible cause of aggregation is interaction between therapeutic protein and surfaces encountered during processing, storage, and administration. Moreover, proteins may adsorb to particles shed from these surfaces. In this work, we studied the immunogenicity of recombinant human interferon beta-1a (rhIFNβ-1a) interacting with glass microparticles, stainless steel microparticles, and polystyrene nanoparticles. At physiological pH, rhIFNβ-1a readily adsorbed to the particles, while the degree of adsorption was influenced by the ionic strength of the phosphate buffer. Front-face fluorescence showed that the tertiary structure of rhIFNβ-1a slightly changed upon adsorption to glass. The interaction with stainless steel microparticles resulted in increased levels of aggregates in the free protein fraction. Furthermore, protein adsorbed to stainless steel microparticles was more difficult to desorb than protein adsorbed to glass. Incubation with stainless steel considerably enhanced the immunogenicity of rhIFNβ-1a in transgenic mice immune tolerant for human interferon beta. The protein fraction adsorbed on stainless steel particles was responsible for this. In conclusion, rhIFNβ-1a adsorbs to common hydrophilic surface materials, possibly increasing the immunogenicity of the protein. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.</description><subject>Adsorption</subject><subject>alpha -Interferon</subject><subject>Animals</subject><subject>beta -Interferon</subject><subject>Biological and medical sciences</subject><subject>Buffers</subject><subject>Chromium</subject><subject>Fluorescence</subject><subject>fluorescence spectroscopy</subject><subject>General pharmacology</subject><subject>Glass - chemistry</subject><subject>Humans</subject><subject>Hydrogen-Ion Concentration</subject><subject>Immune Tolerance</subject><subject>Immunogenicity</subject><subject>Interferon</subject><subject>Interferon beta-1a</subject><subject>Interferon-beta - chemistry</subject><subject>Interferon-beta - immunology</subject><subject>Ionic strength</subject><subject>Medical sciences</subject><subject>Metals</subject><subject>Metals - chemistry</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>microparticles</subject><subject>Multiple sclerosis</subject><subject>nanoparticles</subject><subject>Nanoparticles - chemistry</subject><subject>Osmolar Concentration</subject><subject>pH effects</subject><subject>Pharmaceutical technology. Pharmaceutical industry</subject><subject>Pharmacology. Drug treatments</subject><subject>Phosphate</subject><subject>polystyrene</subject><subject>Polystyrenes - chemistry</subject><subject>protein aggregates</subject><subject>Protein structure</subject><subject>Protein Structure, Tertiary</subject><subject>recombinant human interferon beta</subject><subject>Recombinant Proteins - chemistry</subject><subject>Recombinant Proteins - immunology</subject><subject>stainless steel</subject><subject>Surface Properties</subject><subject>Tertiary structure</subject><subject>Transgenic mice</subject><subject>transgenics</subject><issn>0022-3549</issn><issn>1520-6017</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90V1v0zAUBuAIgVgZXPAHUCSEAGnZ_BknlzCxrmiFioG4tBznZLgkdrEdRv89LumGhIAbW5afc47sN8seY3SMESIn6004JkQwdiebYU5QUSIs7mazdEcKyll9kD0IYY0QKhHn97MDgmtc1RWdZW4xDKN1V2CNNnGbuy7_ANoNjbHKxvx8HJTNFzaC78A7m7-GqKaz0tHYq_zaxC_5SvlodA9hVz_vVQhH-TLJ_ihXts1Xrt-GuPVg4WF2r1N9gEf7_TD7dPbm4-l5cfF-vjh9dVFoVgtWUMwR022naN0yLDjjqgJRt01ddiwtWmPd1MCoUrTpGtoQ1QpCmO6qCtJKD7PnU9-Nd99GCFEOJmjoe2XBjUHWiNclY5gl-eK_Eqe_rAUtCUr06R907UZv0zsk5ljQqsKIJPVyUtq7EDx0cuPNoPw2tZK7vGTKS_7KK9kn-45jM0B7K28CSuDZHqigVd95ZbUJvx3niAu0a3QyuWvTw_bfE-Xb1eXN6GKqMCHCj9sK5b_KUlDB5ed3czlf4jM-F5dymTydPKTYvhvwMmgDVkNrPOgoW2f-8sCf4oXM1w</recordid><startdate>201201</startdate><enddate>201201</enddate><creator>Van Beers, Miranda M.C.</creator><creator>Gilli, Francesca</creator><creator>Schellekens, Huub</creator><creator>Randolph, Theodore W.</creator><creator>Jiskoot, Wim</creator><general>Elsevier Inc</general><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><general>American Pharmaceutical Association</general><general>Elsevier Limited</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>201201</creationdate><title>Immunogenicity of Recombinant Human Interferon Beta Interacting with Particles of Glass, Metal, and Polystyrene</title><author>Van Beers, Miranda M.C. ; Gilli, Francesca ; Schellekens, Huub ; Randolph, Theodore W. ; Jiskoot, Wim</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4974-31504cdfa39d417545a8e79db96f4b96cc1cb9e43aa3bfb3b2ad7224cf88e4cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adsorption</topic><topic>alpha -Interferon</topic><topic>Animals</topic><topic>beta -Interferon</topic><topic>Biological and medical sciences</topic><topic>Buffers</topic><topic>Chromium</topic><topic>Fluorescence</topic><topic>fluorescence spectroscopy</topic><topic>General pharmacology</topic><topic>Glass - chemistry</topic><topic>Humans</topic><topic>Hydrogen-Ion Concentration</topic><topic>Immune Tolerance</topic><topic>Immunogenicity</topic><topic>Interferon</topic><topic>Interferon beta-1a</topic><topic>Interferon-beta - chemistry</topic><topic>Interferon-beta - immunology</topic><topic>Ionic strength</topic><topic>Medical sciences</topic><topic>Metals</topic><topic>Metals - chemistry</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>microparticles</topic><topic>Multiple sclerosis</topic><topic>nanoparticles</topic><topic>Nanoparticles - chemistry</topic><topic>Osmolar Concentration</topic><topic>pH effects</topic><topic>Pharmaceutical technology. Pharmaceutical industry</topic><topic>Pharmacology. Drug treatments</topic><topic>Phosphate</topic><topic>polystyrene</topic><topic>Polystyrenes - chemistry</topic><topic>protein aggregates</topic><topic>Protein structure</topic><topic>Protein Structure, Tertiary</topic><topic>recombinant human interferon beta</topic><topic>Recombinant Proteins - chemistry</topic><topic>Recombinant Proteins - immunology</topic><topic>stainless steel</topic><topic>Surface Properties</topic><topic>Tertiary structure</topic><topic>Transgenic mice</topic><topic>transgenics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Van Beers, Miranda M.C.</creatorcontrib><creatorcontrib>Gilli, Francesca</creatorcontrib><creatorcontrib>Schellekens, Huub</creatorcontrib><creatorcontrib>Randolph, Theodore W.</creatorcontrib><creatorcontrib>Jiskoot, Wim</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Van Beers, Miranda M.C.</au><au>Gilli, Francesca</au><au>Schellekens, Huub</au><au>Randolph, Theodore W.</au><au>Jiskoot, Wim</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunogenicity of Recombinant Human Interferon Beta Interacting with Particles of Glass, Metal, and Polystyrene</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J. Pharm. Sci</addtitle><date>2012-01</date><risdate>2012</risdate><volume>101</volume><issue>1</issue><spage>187</spage><epage>199</epage><pages>187-199</pages><issn>0022-3549</issn><issn>1520-6017</issn><eissn>1520-6017</eissn><coden>JPMSAE</coden><abstract>Aggregates play a major role in the immunogenicity of recombinant human interferon beta (rhIFNβ), a protein used to treat multiple sclerosis. A possible cause of aggregation is interaction between therapeutic protein and surfaces encountered during processing, storage, and administration. Moreover, proteins may adsorb to particles shed from these surfaces. In this work, we studied the immunogenicity of recombinant human interferon beta-1a (rhIFNβ-1a) interacting with glass microparticles, stainless steel microparticles, and polystyrene nanoparticles. At physiological pH, rhIFNβ-1a readily adsorbed to the particles, while the degree of adsorption was influenced by the ionic strength of the phosphate buffer. Front-face fluorescence showed that the tertiary structure of rhIFNβ-1a slightly changed upon adsorption to glass. The interaction with stainless steel microparticles resulted in increased levels of aggregates in the free protein fraction. Furthermore, protein adsorbed to stainless steel microparticles was more difficult to desorb than protein adsorbed to glass. Incubation with stainless steel considerably enhanced the immunogenicity of rhIFNβ-1a in transgenic mice immune tolerant for human interferon beta. The protein fraction adsorbed on stainless steel particles was responsible for this. In conclusion, rhIFNβ-1a adsorbs to common hydrophilic surface materials, possibly increasing the immunogenicity of the protein. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.</abstract><cop>Hoboken</cop><pub>Elsevier Inc</pub><pmid>21918983</pmid><doi>10.1002/jps.22744</doi><tpages>13</tpages></addata></record> |
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| subjects | Adsorption alpha -Interferon Animals beta -Interferon Biological and medical sciences Buffers Chromium Fluorescence fluorescence spectroscopy General pharmacology Glass - chemistry Humans Hydrogen-Ion Concentration Immune Tolerance Immunogenicity Interferon Interferon beta-1a Interferon-beta - chemistry Interferon-beta - immunology Ionic strength Medical sciences Metals Metals - chemistry Mice Mice, Inbred C57BL Mice, Transgenic microparticles Multiple sclerosis nanoparticles Nanoparticles - chemistry Osmolar Concentration pH effects Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Phosphate polystyrene Polystyrenes - chemistry protein aggregates Protein structure Protein Structure, Tertiary recombinant human interferon beta Recombinant Proteins - chemistry Recombinant Proteins - immunology stainless steel Surface Properties Tertiary structure Transgenic mice transgenics |
| title | Immunogenicity of Recombinant Human Interferon Beta Interacting with Particles of Glass, Metal, and Polystyrene |
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