A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice
The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immuniza...
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MDPI AG
2023-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/238 |
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| author | Rushit N. Lodaya Amey P. Kanitkar Asma Ashraf Douty Bamba Mansoor M. Amiji Derek T. O’Hagan |
| author_facet | Rushit N. Lodaya Amey P. Kanitkar Asma Ashraf Douty Bamba Mansoor M. Amiji Derek T. O’Hagan |
| author_sort | Rushit N. Lodaya |
| collection | DOAJ |
| description | The development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse. |
| first_indexed | 2024-03-09T11:27:52Z |
| format | Article |
| id | doaj.art-c0bf05fd78584559baf39398c77b6cd2 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:27:52Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-c0bf05fd78584559baf39398c77b6cd22023-11-30T23:59:37ZengMDPI AGPharmaceutics1999-49232023-01-0115123810.3390/pharmaceutics15010238A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in MiceRushit N. Lodaya0Amey P. Kanitkar1Asma Ashraf2Douty Bamba3Mansoor M. Amiji4Derek T. O’Hagan5Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, USAGSK, Rockville Centre for Vaccines Research, Rockville, MD 20850, USAGSK, Rockville Centre for Vaccines Research, Rockville, MD 20850, USAGSK, Rockville Centre for Vaccines Research, Rockville, MD 20850, USADepartment of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, MA 02115, USAGSK, Rockville Centre for Vaccines Research, Rockville, MD 20850, USAThe development of new vaccine adjuvants represents a key approach to improvingi the immune responses to recombinant vaccine antigens. Emulsion adjuvants, such as AS03 and MF59, in combination with influenza vaccines, have allowed antigen dose sparing, greater breadth of responses and fewer immunizations. It has been demonstrated previously that emulsion adjuvants can be prepared using a simple, low-shear process of self-emulsification (SE). The role of alpha tocopherol as an immune potentiator in emulsion adjuvants is clear from the success of AS03 in pandemic responses, both to influenza and COVID-19. Although it was a significant formulation challenge to include alpha tocopherol in an emulsion prepared by a low-shear process, the resultant self-emulsifying adjuvant system (SE-AS) showed a comparable effect to the established AS03 when used with a quadrivalent influenza vaccine (QIV). In this paper, we first optimized the SE-AS with alpha tocopherol to create SE-AS44, which allowed the emulsion to be sterile-filtered. Then, we compared the in vitro cell activation cytokine profile of SE-AS44 with the self-emulsifying adjuvant 160 (SEA160), a squalene-only adjuvant. In addition, we evaluated SE-AS44 and SEA160 competitively, in combination with a recombinant cytomegalovirus (CMV) pentamer antigen mouse.https://www.mdpi.com/1999-4923/15/1/238adjuvantsalpha-tocopherolnanoemulsionsvaccine deliveryself-emulsification |
| spellingShingle | Rushit N. Lodaya Amey P. Kanitkar Asma Ashraf Douty Bamba Mansoor M. Amiji Derek T. O’Hagan A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice Pharmaceutics adjuvants alpha-tocopherol nanoemulsions vaccine delivery self-emulsification |
| title | A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice |
| title_full | A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice |
| title_fullStr | A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice |
| title_full_unstemmed | A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice |
| title_short | A Self-Emulsified Adjuvant System Containing the Immune Potentiator Alpha Tocopherol Induces Higher Neutralizing Antibody Responses than a Squalene-Only Emulsion When Evaluated with a Recombinant Cytomegalovirus (CMV) Pentamer Antigen in Mice |
| title_sort | self emulsified adjuvant system containing the immune potentiator alpha tocopherol induces higher neutralizing antibody responses than a squalene only emulsion when evaluated with a recombinant cytomegalovirus cmv pentamer antigen in mice |
| topic | adjuvants alpha-tocopherol nanoemulsions vaccine delivery self-emulsification |
| url | https://www.mdpi.com/1999-4923/15/1/238 |
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