Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens
© 2020 The Authors A two-step developability assessment workflow is described to screen variants of recombinant protein antigens under various formulation conditions to rapidly identify stable, aluminum-adjuvanted, multi-dose vaccine candidates. For proof-of-concept, a series of sequence variants of...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
|
| Online Access: | https://hdl.handle.net/1721.1/134368 |
| _version_ | 1826210618031472640 |
|---|---|
| author | Sawant, Nishant Kaur, Kawaljit Holland, David A Hickey, John M Agarwal, Sanjeev Brady, Joseph R Dalvie, Neil C Tracey, Mary Kate Velez-Suberbie, M Lourdes Morris, Stephen A Jacob, Shaleem I Bracewell, Daniel G Mukhopadhyay, Tarit K Love, Kerry R Love, J Christopher Joshi, Sangeeta B Volkin, David B |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Sawant, Nishant Kaur, Kawaljit Holland, David A Hickey, John M Agarwal, Sanjeev Brady, Joseph R Dalvie, Neil C Tracey, Mary Kate Velez-Suberbie, M Lourdes Morris, Stephen A Jacob, Shaleem I Bracewell, Daniel G Mukhopadhyay, Tarit K Love, Kerry R Love, J Christopher Joshi, Sangeeta B Volkin, David B |
| author_sort | Sawant, Nishant |
| collection | MIT |
| description | © 2020 The Authors A two-step developability assessment workflow is described to screen variants of recombinant protein antigens under various formulation conditions to rapidly identify stable, aluminum-adjuvanted, multi-dose vaccine candidates. For proof-of-concept, a series of sequence variants of the recombinant non-replicating rotavirus (NRRV) P[8] protein antigen (produced in Komagataella phaffii) were compared in terms of primary structure, post-translational modifications, antibody binding, conformational stability, relative solubility and preservative compatibility. Based on these results, promising P[8] variants were down-selected and the impact of key formulation conditions on storage stability was examined (e.g., presence or absence of the aluminum-adjuvant Alhydrogel and the preservative thimerosal) as measured by differential scanning calorimetry (DSC) and antibody binding assays. Good correlations between rapidly-generated developability screening data and storage stability profiles (12 weeks at various temperatures) were observed for aluminum-adsorbed P[8] antigens. These findings were extended and confirmed using variants of a second NRRV antigen, P[4]. These case-study results with P[8] and P[4] NRRV variants are discussed in terms of using this vaccine formulation developability workflow to better inform and optimize formulation design with a wide variety of recombinant protein antigens, with the long-term goal of rapidly and cost-efficiently identifying low-cost vaccine formulations for use in low and middle income countries. |
| first_indexed | 2024-09-23T14:52:29Z |
| format | Article |
| id | mit-1721.1/134368 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:52:29Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1343682023-09-19T18:23:47Z Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens Sawant, Nishant Kaur, Kawaljit Holland, David A Hickey, John M Agarwal, Sanjeev Brady, Joseph R Dalvie, Neil C Tracey, Mary Kate Velez-Suberbie, M Lourdes Morris, Stephen A Jacob, Shaleem I Bracewell, Daniel G Mukhopadhyay, Tarit K Love, Kerry R Love, J Christopher Joshi, Sangeeta B Volkin, David B Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT © 2020 The Authors A two-step developability assessment workflow is described to screen variants of recombinant protein antigens under various formulation conditions to rapidly identify stable, aluminum-adjuvanted, multi-dose vaccine candidates. For proof-of-concept, a series of sequence variants of the recombinant non-replicating rotavirus (NRRV) P[8] protein antigen (produced in Komagataella phaffii) were compared in terms of primary structure, post-translational modifications, antibody binding, conformational stability, relative solubility and preservative compatibility. Based on these results, promising P[8] variants were down-selected and the impact of key formulation conditions on storage stability was examined (e.g., presence or absence of the aluminum-adjuvant Alhydrogel and the preservative thimerosal) as measured by differential scanning calorimetry (DSC) and antibody binding assays. Good correlations between rapidly-generated developability screening data and storage stability profiles (12 weeks at various temperatures) were observed for aluminum-adsorbed P[8] antigens. These findings were extended and confirmed using variants of a second NRRV antigen, P[4]. These case-study results with P[8] and P[4] NRRV variants are discussed in terms of using this vaccine formulation developability workflow to better inform and optimize formulation design with a wide variety of recombinant protein antigens, with the long-term goal of rapidly and cost-efficiently identifying low-cost vaccine formulations for use in low and middle income countries. 2021-10-27T20:04:39Z 2021-10-27T20:04:39Z 2021 2021-06-22T16:46:07Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/134368 en 10.1016/j.xphs.2020.11.039 Journal of Pharmaceutical Sciences Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Sawant, Nishant Kaur, Kawaljit Holland, David A Hickey, John M Agarwal, Sanjeev Brady, Joseph R Dalvie, Neil C Tracey, Mary Kate Velez-Suberbie, M Lourdes Morris, Stephen A Jacob, Shaleem I Bracewell, Daniel G Mukhopadhyay, Tarit K Love, Kerry R Love, J Christopher Joshi, Sangeeta B Volkin, David B Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens |
| title | Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens |
| title_full | Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens |
| title_fullStr | Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens |
| title_full_unstemmed | Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens |
| title_short | Rapid Developability Assessments to Formulate Recombinant Protein Antigens as Stable, Low-Cost, Multi-Dose Vaccine Candidates: Case-Study With Non-Replicating Rotavirus (NRRV) Vaccine Antigens |
| title_sort | rapid developability assessments to formulate recombinant protein antigens as stable low cost multi dose vaccine candidates case study with non replicating rotavirus nrrv vaccine antigens |
| url | https://hdl.handle.net/1721.1/134368 |
| work_keys_str_mv | AT sawantnishant rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT kaurkawaljit rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT hollanddavida rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT hickeyjohnm rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT agarwalsanjeev rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT bradyjosephr rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT dalvieneilc rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT traceymarykate rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT velezsuberbiemlourdes rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT morrisstephena rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT jacobshaleemi rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT bracewelldanielg rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT mukhopadhyaytaritk rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT lovekerryr rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT lovejchristopher rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT joshisangeetab rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens AT volkindavidb rapiddevelopabilityassessmentstoformulaterecombinantproteinantigensasstablelowcostmultidosevaccinecandidatescasestudywithnonreplicatingrotavirusnrrvvaccineantigens |