Route and antigen shape immunity to dmLT-adjuvanted vaccines to a greater extent than biochemical stress or formulation excipients
Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved..
A key aspect to vaccine efficacy is formulation stability. Biochemical evaluations provide information on optimal compositions or thermal stability but are routinely validated by ex vivo analysis and not efficacy in animal models. Here we assessed formulations identified to improve or reduce stability of the mucosal adjuvant dmLT being investigated in polio and enterotoxigenic E. coli (ETEC) clinical vaccines. We observed biochemical changes to dmLT protein with formulation or thermal stress, including aggregation or subunit dissociation or alternatively resistance against these changes with specific buffer compositions. However, upon injection or mucosal vaccination with ETEC fimbriae adhesin proteins or inactivated polio virus, experimental findings indicated immunization route and co-administered antigen impacted vaccine immunogenicity more so than dmLT formulation stability (or instability). These results indicate the importance of both biochemical and vaccine-derived immunity assessment in formulation optimization. In addition, these studies have implications for use of dmLT in clinical settings and for delivery in resource poor settings.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:41 |
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| Enthalten in: |
Vaccine - 41(2023), 9 vom: 24. Feb., Seite 1589-1601 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Stone, Addison E [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.02.2023 Date Revised 16.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.vaccine.2023.01.033 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a A key aspect to vaccine efficacy is formulation stability. Biochemical evaluations provide information on optimal compositions or thermal stability but are routinely validated by ex vivo analysis and not efficacy in animal models. Here we assessed formulations identified to improve or reduce stability of the mucosal adjuvant dmLT being investigated in polio and enterotoxigenic E. coli (ETEC) clinical vaccines. We observed biochemical changes to dmLT protein with formulation or thermal stress, including aggregation or subunit dissociation or alternatively resistance against these changes with specific buffer compositions. However, upon injection or mucosal vaccination with ETEC fimbriae adhesin proteins or inactivated polio virus, experimental findings indicated immunization route and co-administered antigen impacted vaccine immunogenicity more so than dmLT formulation stability (or instability). These results indicate the importance of both biochemical and vaccine-derived immunity assessment in formulation optimization. In addition, these studies have implications for use of dmLT in clinical settings and for delivery in resource poor settings | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Adjuvant | |
| 650 | 4 | |a ETEC | |
| 650 | 4 | |a Formulation stability | |
| 650 | 4 | |a Mucosal immunity | |
| 650 | 4 | |a Polio | |
| 650 | 4 | |a Vaccine efficacy | |
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| 700 | 1 | |a Trinh, Ivy V |e verfasserin |4 aut | |
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| 700 | 1 | |a Jarand, Curtis W |e verfasserin |4 aut | |
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| 700 | 1 | |a Murrell, Amelie E |e verfasserin |4 aut | |
| 700 | 1 | |a Huerter, Chelsea M |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, William |e verfasserin |4 aut | |
| 700 | 1 | |a Palani, Surya |e verfasserin |4 aut | |
| 700 | 1 | |a Nakanishi, Yukihiro |e verfasserin |4 aut | |
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| 700 | 1 | |a White, Jessica A |e verfasserin |4 aut | |
| 700 | 1 | |a Norton, Elizabeth B |e verfasserin |4 aut | |
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