Feasibility of Freeze-Drying Oil-in-Water Emulsion Adjuvants and Subunit Proteins to Enable Single-Vial Vaccine Drug Products
To generate potent vaccine responses, subunit protein antigens typically require coformulation with an adjuvant. Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However...
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| Veröffentlicht in: | Journal of pharmaceutical sciences 2017-06, Vol.106 (6), p.1490-1498 |
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| creator | Iyer, Vidyashankara Cayatte, Corinne Marshall, Jason D. Sun, Jenny Schneider-Ohrum, Kirsten Maynard, Sean K. Rajani, Gaurav Manohar Bennett, Angie Snell Remmele, Richard L. Bishop, Steve M. McCarthy, Michael P. Muralidhara, Bilikallahalli K. |
| description | To generate potent vaccine responses, subunit protein antigens typically require coformulation with an adjuvant. Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However, most emulsions cannot be readily frozen or lyophilized, on account of the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid coformulation. To circumvent this, current emulsion-formulated vaccines generally require a complex multivial presentation with obvious drawbacks, making a single-vial presentation for such products highly desirable. We describe the development of a stable, lyophilized squalene emulsion adjuvant through innovative formulation and process development approaches. On reconstitution, freeze-dried emulsion preparations were found to have a minimal increase in particle size of ∼20 nm and conferred immunogenicity in BALB/c mice similar in potency to freshly prepared emulsion coformulations in liquid form. |
| doi_str_mv | 10.1016/j.xphs.2017.02.024 |
| format | Article |
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Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However, most emulsions cannot be readily frozen or lyophilized, on account of the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid coformulation. To circumvent this, current emulsion-formulated vaccines generally require a complex multivial presentation with obvious drawbacks, making a single-vial presentation for such products highly desirable. We describe the development of a stable, lyophilized squalene emulsion adjuvant through innovative formulation and process development approaches. On reconstitution, freeze-dried emulsion preparations were found to have a minimal increase in particle size of ∼20 nm and conferred immunogenicity in BALB/c mice similar in potency to freshly prepared emulsion coformulations in liquid form.</description><identifier>ISSN: 0022-3549</identifier><identifier>EISSN: 1520-6017</identifier><identifier>DOI: 10.1016/j.xphs.2017.02.024</identifier><identifier>PMID: 28259764</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adjuvants, Immunologic - chemistry ; Adjuvants, Immunologic - pharmacology ; Animals ; B-Lymphocytes - immunology ; emulsion ; Emulsions - chemistry ; Emulsions - pharmacology ; Epstein-Barr Virus Infections - immunology ; Epstein-Barr Virus Infections - prevention & control ; Female ; formulation ; Freeze Drying - methods ; Herpesvirus 4, Human - immunology ; immune response ; Immunity, Cellular ; lyophilization ; Mice, Inbred C57BL ; Respiratory Syncytial Virus Infections - immunology ; Respiratory Syncytial Virus Infections - prevention & control ; Respiratory Syncytial Viruses - immunology ; Squalene - chemistry ; Squalene - pharmacology ; T-Lymphocytes - immunology ; vaccine adjuvants ; Viral Vaccines - chemistry ; Viral Vaccines - immunology ; Viral Vaccines - pharmacology</subject><ispartof>Journal of pharmaceutical sciences, 2017-06, Vol.106 (6), p.1490-1498</ispartof><rights>2017 American Pharmacists Association</rights><rights>Copyright © 2017 American Pharmacists Association®. 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Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However, most emulsions cannot be readily frozen or lyophilized, on account of the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid coformulation. To circumvent this, current emulsion-formulated vaccines generally require a complex multivial presentation with obvious drawbacks, making a single-vial presentation for such products highly desirable. We describe the development of a stable, lyophilized squalene emulsion adjuvant through innovative formulation and process development approaches. On reconstitution, freeze-dried emulsion preparations were found to have a minimal increase in particle size of ∼20 nm and conferred immunogenicity in BALB/c mice similar in potency to freshly prepared emulsion coformulations in liquid form.</description><subject>Adjuvants, Immunologic - chemistry</subject><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Animals</subject><subject>B-Lymphocytes - immunology</subject><subject>emulsion</subject><subject>Emulsions - chemistry</subject><subject>Emulsions - pharmacology</subject><subject>Epstein-Barr Virus Infections - immunology</subject><subject>Epstein-Barr Virus Infections - prevention & control</subject><subject>Female</subject><subject>formulation</subject><subject>Freeze Drying - methods</subject><subject>Herpesvirus 4, Human - immunology</subject><subject>immune response</subject><subject>Immunity, Cellular</subject><subject>lyophilization</subject><subject>Mice, Inbred C57BL</subject><subject>Respiratory Syncytial Virus Infections - immunology</subject><subject>Respiratory Syncytial Virus Infections - prevention & control</subject><subject>Respiratory Syncytial Viruses - immunology</subject><subject>Squalene - chemistry</subject><subject>Squalene - pharmacology</subject><subject>T-Lymphocytes - immunology</subject><subject>vaccine adjuvants</subject><subject>Viral Vaccines - chemistry</subject><subject>Viral Vaccines - immunology</subject><subject>Viral Vaccines - pharmacology</subject><issn>0022-3549</issn><issn>1520-6017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kF9rFDEUxYModq1-AR8kj75kTTLJJAFfSrurQqFCtT6GTOZuzZLNrPlTXMHv7ixbfRQOXO7ldw7cg9BrRpeMsv7ddvlz_70sOWVqSfks8QQtmOSU9PPpKVpQyjnppDBn6EUpW0ppT6V8js645tKoXizQ7zW4EoYQQz3gaYPXGeAXkKt8COke34RIQiLfXIWMV7sWS5gSvhi37cGlWrBLI75tQ0uh4s95qhBSwXXCq-SGCPh2zohA7oKL-M55HxLgq9zuj-zYfC0v0bONiwVePc5z9HW9-nL5kVzffPh0eXFNfCf7SrQww6bXQoFkkvJB63EwxnNjjBi50PPuldRMglKdkV70WkrGlPBgvBtMd47ennL3efrRoFS7C8VDjC7B1IplWgmlO8XVjPIT6vNUSoaN3eewc_lgGbXH2u3WHmu3x9ot5bPEbHrzmN-GHYz_LH97noH3JwDmLx8CZFt8gORhDBl8teMU_pf_B1Hlk9Y</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Iyer, Vidyashankara</creator><creator>Cayatte, Corinne</creator><creator>Marshall, Jason D.</creator><creator>Sun, Jenny</creator><creator>Schneider-Ohrum, Kirsten</creator><creator>Maynard, Sean K.</creator><creator>Rajani, Gaurav Manohar</creator><creator>Bennett, Angie Snell</creator><creator>Remmele, Richard L.</creator><creator>Bishop, Steve M.</creator><creator>McCarthy, Michael P.</creator><creator>Muralidhara, Bilikallahalli K.</creator><general>Elsevier Inc</general><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>7X8</scope></search><sort><creationdate>201706</creationdate><title>Feasibility of Freeze-Drying Oil-in-Water Emulsion Adjuvants and Subunit Proteins to Enable Single-Vial Vaccine Drug Products</title><author>Iyer, Vidyashankara ; Cayatte, Corinne ; Marshall, Jason D. ; Sun, Jenny ; Schneider-Ohrum, Kirsten ; Maynard, Sean K. ; Rajani, Gaurav Manohar ; Bennett, Angie Snell ; Remmele, Richard L. ; Bishop, Steve M. ; McCarthy, Michael P. ; Muralidhara, Bilikallahalli K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-849bf6847e51502b88db99c29994d24888dc75815e77395c468551174ce9cab93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adjuvants, Immunologic - chemistry</topic><topic>Adjuvants, Immunologic - pharmacology</topic><topic>Animals</topic><topic>B-Lymphocytes - immunology</topic><topic>emulsion</topic><topic>Emulsions - chemistry</topic><topic>Emulsions - pharmacology</topic><topic>Epstein-Barr Virus Infections - immunology</topic><topic>Epstein-Barr Virus Infections - prevention & control</topic><topic>Female</topic><topic>formulation</topic><topic>Freeze Drying - methods</topic><topic>Herpesvirus 4, Human - immunology</topic><topic>immune response</topic><topic>Immunity, Cellular</topic><topic>lyophilization</topic><topic>Mice, Inbred C57BL</topic><topic>Respiratory Syncytial Virus Infections - immunology</topic><topic>Respiratory Syncytial Virus Infections - prevention & control</topic><topic>Respiratory Syncytial Viruses - immunology</topic><topic>Squalene - chemistry</topic><topic>Squalene - pharmacology</topic><topic>T-Lymphocytes - immunology</topic><topic>vaccine adjuvants</topic><topic>Viral Vaccines - chemistry</topic><topic>Viral Vaccines - immunology</topic><topic>Viral Vaccines - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iyer, Vidyashankara</creatorcontrib><creatorcontrib>Cayatte, Corinne</creatorcontrib><creatorcontrib>Marshall, Jason D.</creatorcontrib><creatorcontrib>Sun, Jenny</creatorcontrib><creatorcontrib>Schneider-Ohrum, Kirsten</creatorcontrib><creatorcontrib>Maynard, Sean K.</creatorcontrib><creatorcontrib>Rajani, Gaurav Manohar</creatorcontrib><creatorcontrib>Bennett, Angie Snell</creatorcontrib><creatorcontrib>Remmele, Richard L.</creatorcontrib><creatorcontrib>Bishop, Steve M.</creatorcontrib><creatorcontrib>McCarthy, Michael P.</creatorcontrib><creatorcontrib>Muralidhara, Bilikallahalli K.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iyer, Vidyashankara</au><au>Cayatte, Corinne</au><au>Marshall, Jason D.</au><au>Sun, Jenny</au><au>Schneider-Ohrum, Kirsten</au><au>Maynard, Sean K.</au><au>Rajani, Gaurav Manohar</au><au>Bennett, Angie Snell</au><au>Remmele, Richard L.</au><au>Bishop, Steve M.</au><au>McCarthy, Michael P.</au><au>Muralidhara, Bilikallahalli K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Feasibility of Freeze-Drying Oil-in-Water Emulsion Adjuvants and Subunit Proteins to Enable Single-Vial Vaccine Drug Products</atitle><jtitle>Journal of pharmaceutical sciences</jtitle><addtitle>J Pharm Sci</addtitle><date>2017-06</date><risdate>2017</risdate><volume>106</volume><issue>6</issue><spage>1490</spage><epage>1498</epage><pages>1490-1498</pages><issn>0022-3549</issn><eissn>1520-6017</eissn><abstract>To generate potent vaccine responses, subunit protein antigens typically require coformulation with an adjuvant. Oil-in-water emulsions are among the most widely investigated adjuvants, based on their demonstrated ability to elicit robust antibody and cellular immune responses in the clinic. However, most emulsions cannot be readily frozen or lyophilized, on account of the risk of phase separation, and may have a deleterious effect on protein antigen stability when stored long term as a liquid coformulation. To circumvent this, current emulsion-formulated vaccines generally require a complex multivial presentation with obvious drawbacks, making a single-vial presentation for such products highly desirable. We describe the development of a stable, lyophilized squalene emulsion adjuvant through innovative formulation and process development approaches. On reconstitution, freeze-dried emulsion preparations were found to have a minimal increase in particle size of ∼20 nm and conferred immunogenicity in BALB/c mice similar in potency to freshly prepared emulsion coformulations in liquid form.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28259764</pmid><doi>10.1016/j.xphs.2017.02.024</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of pharmaceutical sciences, 2017-06, Vol.106 (6), p.1490-1498 |
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| subjects | Adjuvants, Immunologic - chemistry Adjuvants, Immunologic - pharmacology Animals B-Lymphocytes - immunology emulsion Emulsions - chemistry Emulsions - pharmacology Epstein-Barr Virus Infections - immunology Epstein-Barr Virus Infections - prevention & control Female formulation Freeze Drying - methods Herpesvirus 4, Human - immunology immune response Immunity, Cellular lyophilization Mice, Inbred C57BL Respiratory Syncytial Virus Infections - immunology Respiratory Syncytial Virus Infections - prevention & control Respiratory Syncytial Viruses - immunology Squalene - chemistry Squalene - pharmacology T-Lymphocytes - immunology vaccine adjuvants Viral Vaccines - chemistry Viral Vaccines - immunology Viral Vaccines - pharmacology |
| title | Feasibility of Freeze-Drying Oil-in-Water Emulsion Adjuvants and Subunit Proteins to Enable Single-Vial Vaccine Drug Products |
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