A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component
Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence...
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| Published in | Frontiers in immunology Vol. 14; p. 1116238 |
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| Main Authors | , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
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Switzerland
Frontiers Media S.A
20.02.2023
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| Abstract | Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.
To characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.
This study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants. |
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| AbstractList | Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.
To characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.
This study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants. BackgroundAdjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.Methods and ResultsTo characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.ConclusionsThis study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants. Adjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.BackgroundAdjuvants are chemical or biological materials that enhance the efficacy of vaccines. A-910823 is a squalene-based emulsion adjuvant used for S-268019-b, a novel vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that is currently in clinical development. Published evidence has demonstrated that A-910823 can enhance the induction of neutralizing antibodies against SARS-CoV-2 in humans and animal models. However, the characteristics and mechanisms of the immune responses induced by A-910823 are not yet known.To characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.Methods and ResultsTo characterize A-910823, we compared the adaptive immune response profile enhanced by A-910823 with that of other adjuvants (AddaVax, QS21, aluminum salt-based adjuvants, and empty lipid nanoparticle [eLNP]) in a murine model. Compared with other adjuvants, A-910823 enhanced humoral immune responses to an equal or greater extent following potent T follicular helper (Tfh) and germinal center B (GCB) cell induction, without inducing a strong systemic inflammatory cytokine response. Furthermore, S-268019-b containing A-910823 adjuvant produced similar results even when given as a booster dose following primary administration of a lipid nanoparticle-encapsulated messenger RNA (mRNA-LNP) vaccine. Preparation of modified A-910823 adjuvants to identify which components of A-910823 play a role in driving the adjuvant effect and detailed evaluation of the immunological characteristics induced by each adjuvant showed that the induction of humoral immunity and Tfh and GCB cell induction in A-910823 were dependent on α-tocopherol. Finally, we revealed that the recruitment of inflammatory cells to the draining lymph nodes and induction of serum cytokines and chemokines by A-910823 were also dependent on the α-tocopherol component.This study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants.ConclusionsThis study demonstrates that the novel adjuvant A-910823 is capable of robust Tfh cell induction and humoral immune responses, even when given as a booster dose. The findings also emphasize that α-tocopherol drives the potent Tfh-inducing adjuvant function of A-910823. Overall, our data provide key information that may inform the future production of improved adjuvants. |
| Author | Tajiri, Minako Asaoka, Yoshiji Nakagawa, Takayuki Kobiyama, Kouji Hayashi, Tomoya Nishinaka, Anri Hirose, Jun Hayata, Atsushi Hashimoto, Masayuki Ishida, Satoru Omoto, Shinya Nagira, Morio Yoshioka, Yuya Onishi, Motoyasu Yanagida, Yosuke Ishii, Ken J. |
| AuthorAffiliation | 3 International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo , Tokyo , Japan 4 Formulation R&D Laboratory, Shionogi & Co., Ltd. , Osaka , Japan 5 Laboratory for Drug Discovery and Development, Shionogi & Co., Ltd. , Osaka , Japan 6 Laboratory for Bio-Modality Research, Shionogi & Co. , Osaka , Japan 1 Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd. , Osaka , Japan 8 Laboratory of Vaccine Science, Immunology Frontier Research Center, Osaka University , Osaka , Japan 7 Vaccine and Adjuvant Research Center (CVAR), National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN) , Osaka , Japan 2 Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo , Japan |
| AuthorAffiliation_xml | – name: 3 International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo , Tokyo , Japan – name: 8 Laboratory of Vaccine Science, Immunology Frontier Research Center, Osaka University , Osaka , Japan – name: 1 Laboratory for Bio-Drug Discovery, Shionogi & Co., Ltd. , Osaka , Japan – name: 2 Division of Vaccine Science, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo , Japan – name: 4 Formulation R&D Laboratory, Shionogi & Co., Ltd. , Osaka , Japan – name: 6 Laboratory for Bio-Modality Research, Shionogi & Co. , Osaka , Japan – name: 5 Laboratory for Drug Discovery and Development, Shionogi & Co., Ltd. , Osaka , Japan – name: 7 Vaccine and Adjuvant Research Center (CVAR), National Institute of Biomedical Innovation, Health and Nutrition (NIBIOHN) , Osaka , Japan |
| Author_xml | – sequence: 1 givenname: Yuya surname: Yoshioka fullname: Yoshioka, Yuya – sequence: 2 givenname: Kouji surname: Kobiyama fullname: Kobiyama, Kouji – sequence: 3 givenname: Tomoya surname: Hayashi fullname: Hayashi, Tomoya – sequence: 4 givenname: Motoyasu surname: Onishi fullname: Onishi, Motoyasu – sequence: 5 givenname: Yosuke surname: Yanagida fullname: Yanagida, Yosuke – sequence: 6 givenname: Takayuki surname: Nakagawa fullname: Nakagawa, Takayuki – sequence: 7 givenname: Masayuki surname: Hashimoto fullname: Hashimoto, Masayuki – sequence: 8 givenname: Anri surname: Nishinaka fullname: Nishinaka, Anri – sequence: 9 givenname: Jun surname: Hirose fullname: Hirose, Jun – sequence: 10 givenname: Yoshiji surname: Asaoka fullname: Asaoka, Yoshiji – sequence: 11 givenname: Minako surname: Tajiri fullname: Tajiri, Minako – sequence: 12 givenname: Atsushi surname: Hayata fullname: Hayata, Atsushi – sequence: 13 givenname: Satoru surname: Ishida fullname: Ishida, Satoru – sequence: 14 givenname: Shinya surname: Omoto fullname: Omoto, Shinya – sequence: 15 givenname: Morio surname: Nagira fullname: Nagira, Morio – sequence: 16 givenname: Ken J. surname: Ishii fullname: Ishii, Ken J. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36891311$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright © 2023 Yoshioka, Kobiyama, Hayashi, Onishi, Yanagida, Nakagawa, Hashimoto, Nishinaka, Hirose, Asaoka, Tajiri, Hayata, Ishida, Omoto, Nagira and Ishii. Copyright © 2023 Yoshioka, Kobiyama, Hayashi, Onishi, Yanagida, Nakagawa, Hashimoto, Nishinaka, Hirose, Asaoka, Tajiri, Hayata, Ishida, Omoto, Nagira and Ishii 2023 Yoshioka, Kobiyama, Hayashi, Onishi, Yanagida, Nakagawa, Hashimoto, Nishinaka, Hirose, Asaoka, Tajiri, Hayata, Ishida, Omoto, Nagira and Ishii |
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| Keywords | mouse vaccine adjuvant immune response severe acute respiratory syndrome coronavirus 2 Tfh S-268019-b A-910823 |
| Language | English |
| License | Copyright © 2023 Yoshioka, Kobiyama, Hayashi, Onishi, Yanagida, Nakagawa, Hashimoto, Nishinaka, Hirose, Asaoka, Tajiri, Hayata, Ishida, Omoto, Nagira and Ishii. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Elke Bergmann-Leitner, Walter Reed Army Institute of Research, United States Reviewed by: Kentner Singleton, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), United States; Mehdi Mahdavi, Motamed Cancer Institute, Iran; Carolyn M. Nielsen, Department of Biochemistry, University of Oxford, United Kingdom This article was submitted to Vaccines and Molecular Therapeutics, a section of the journal Frontiers in Immunology |
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| SubjectTerms | A-910823 adjuvant Adjuvants, Immunologic - pharmacology Adjuvants, Pharmaceutic alpha-Tocopherol - pharmacology Animals COVID-19 Emulsions Humans Immunity, Humoral Immunology Mice mouse S-268019-b SARS-CoV-2 Squalene - pharmacology T Follicular Helper Cells Tfh vaccine |
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| Title | A-910823, a squalene-based emulsion adjuvant, induces T follicular helper cells and humoral immune responses via α-tocopherol component |
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