Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus
Background: Vaccines comprising recombinant subunit proteins are well-suited to low-cost and high-volume production for global use. The design of manufacturing processes to produce subunit vaccines depends, however, on the inherent biophysical traits presented by an individual antigen of interest. N...
| Autores principales: | , , , , , , , , , , , , , , , , , , |
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| Formato: | info:ar-repo/semantics/artículo |
| Lenguaje: | Inglés |
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BMC
2021
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12123/10760 https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-021-01583-6 https://doi.org/10.1186/s12934-021-01583-6 |
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| author | Dalvie, Neil C. Brady, Joseph R. Crowell, Laura E. Tracey, Mary Kate Biedermann, Andrew M. Kaur, Kawaljit Hickey, John M. Kristensen II, D. Lee Bonnyman, Alexandra D. Rodriguez-Aponte, Sergio A. Whittaker, Charles A. Bok, Marina Vega, Celina Guadalupe Mukhopadhyay, Tarit K. Joshi, Sangeeta B. Volkin, David B. Parreño, Gladys Love, Kerry R. Love, J. Christopher |
| author_browse | Biedermann, Andrew M. Bok, Marina Bonnyman, Alexandra D. Brady, Joseph R. Crowell, Laura E. Dalvie, Neil C. Hickey, John M. Joshi, Sangeeta B. Kaur, Kawaljit Kristensen II, D. Lee Love, J. Christopher Love, Kerry R. Mukhopadhyay, Tarit K. Parreño, Gladys Rodriguez-Aponte, Sergio A. Tracey, Mary Kate Vega, Celina Guadalupe Volkin, David B. Whittaker, Charles A. |
| author_facet | Dalvie, Neil C. Brady, Joseph R. Crowell, Laura E. Tracey, Mary Kate Biedermann, Andrew M. Kaur, Kawaljit Hickey, John M. Kristensen II, D. Lee Bonnyman, Alexandra D. Rodriguez-Aponte, Sergio A. Whittaker, Charles A. Bok, Marina Vega, Celina Guadalupe Mukhopadhyay, Tarit K. Joshi, Sangeeta B. Volkin, David B. Parreño, Gladys Love, Kerry R. Love, J. Christopher |
| author_sort | Dalvie, Neil C. |
| collection | INTA Digital |
| description | Background: Vaccines comprising recombinant subunit proteins are well-suited to low-cost and high-volume production for global use. The design of manufacturing processes to produce subunit vaccines depends, however, on the inherent biophysical traits presented by an individual antigen of interest. New candidate antigens typically require developing custom processes for each one and may require unique steps to ensure sufficient yields without product-related variants.
Results: We describe a holistic approach for the molecular design of recombinant protein antigens—considering both their manufacturability and antigenicity—informed by bioinformatic analyses such as RNA-seq, ribosome profiling, and sequence-based prediction tools. We demonstrate this approach by engineering the product sequences of a trivalent non-replicating rotavirus vaccine (NRRV) candidate to improve titers and mitigate product variants caused by N-terminal truncation, hypermannosylation, and aggregation. The three engineered NRRV antigens retained their original antigenicity and immunogenicity, while their improved manufacturability enabled concomitant production and purification of all three serotypes in a single, end-to-end perfusion-based process using the biotechnical yeast Komagataella phaffii.
Conclusions: This study demonstrates that molecular engineering of subunit antigens using advanced genomic methods can facilitate their manufacturing in continuous production. Such capabilities have potential to lower the cost and volumetric requirements in manufacturing vaccines based on recombinant protein subunits. |
| format | info:ar-repo/semantics/artículo |
| id | INTA10760 |
| institution | Instituto Nacional de Tecnología Agropecuaria (INTA -Argentina) |
| language | Inglés |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | BMC |
| publisherStr | BMC |
| record_format | dspace |
| spelling | INTA107602021-11-12T13:58:34Z Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus Dalvie, Neil C. Brady, Joseph R. Crowell, Laura E. Tracey, Mary Kate Biedermann, Andrew M. Kaur, Kawaljit Hickey, John M. Kristensen II, D. Lee Bonnyman, Alexandra D. Rodriguez-Aponte, Sergio A. Whittaker, Charles A. Bok, Marina Vega, Celina Guadalupe Mukhopadhyay, Tarit K. Joshi, Sangeeta B. Volkin, David B. Parreño, Gladys Love, Kerry R. Love, J. Christopher Vacuna Antígenos Genética Molecular Pichia pastoris Vaccines Rotavirus Antigens Molecular Genetics Background: Vaccines comprising recombinant subunit proteins are well-suited to low-cost and high-volume production for global use. The design of manufacturing processes to produce subunit vaccines depends, however, on the inherent biophysical traits presented by an individual antigen of interest. New candidate antigens typically require developing custom processes for each one and may require unique steps to ensure sufficient yields without product-related variants. Results: We describe a holistic approach for the molecular design of recombinant protein antigens—considering both their manufacturability and antigenicity—informed by bioinformatic analyses such as RNA-seq, ribosome profiling, and sequence-based prediction tools. We demonstrate this approach by engineering the product sequences of a trivalent non-replicating rotavirus vaccine (NRRV) candidate to improve titers and mitigate product variants caused by N-terminal truncation, hypermannosylation, and aggregation. The three engineered NRRV antigens retained their original antigenicity and immunogenicity, while their improved manufacturability enabled concomitant production and purification of all three serotypes in a single, end-to-end perfusion-based process using the biotechnical yeast Komagataella phaffii. Conclusions: This study demonstrates that molecular engineering of subunit antigens using advanced genomic methods can facilitate their manufacturing in continuous production. Such capabilities have potential to lower the cost and volumetric requirements in manufacturing vaccines based on recombinant protein subunits. Instituto de Virología Fil: Dalvie, Neil C. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos Fil: Dalvie, Neil C. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Brady, Joseph R. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos Fil: Brady, Joseph R. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Crowell, Laura E. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos Fil: Crowell, Laura E. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Tracey, Mary Kate. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Biedermann, Andrew M. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos Fil: Biedermann, Andrew M. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Kaur, Kawaljit. University of Kansas. Vaccine Analytics and Formulation Center. Department of Pharmaceutical Chemistry; Estados Unidos Fil: Hickey, John M. University of Kansas. Vaccine Analytics and Formulation Center. Department of Pharmaceutical Chemistry; Estados Unidos Fil: Kristensen II, D. Lee. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Bonnyman, Alexandra D. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos Fil: Bonnyman, Alexandra D. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Rodriguez-Aponte, Sergio A. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Rodriguez-Aponte, Sergio A. Massachusetts Institute of Technology. Department of Biological Engineering; Estados Unidos Fil: Whittaker, Charles A. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina Fil: Bok, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vega, Celina Guadalupe. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina Fil: Vega, Celina Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Mukhopadhyay, Tarit K. University College London. Department of Biochemical Engineering; Reino Unidos Fil: Joshi, Sangeeta B. University of Kansas. Vaccine Analytics and Formulation Center. Department of Pharmaceutical Chemistry; Estados Unidos Fil: Volkin, David B. University of Kansas. Vaccine Analytics and Formulation Center. Department of Pharmaceutical Chemistry; Estados Unidos Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina Fil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Love, Kerry R. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos Fil: Love, Kerry R. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos Fil: Love, J. Christopher. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos Fil: Love, J. Christopher. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos 2021-11-12T13:55:22Z 2021-11-12T13:55:22Z 2021-05 info:ar-repo/semantics/artículo info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/20.500.12123/10760 https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-021-01583-6 1475-2859 https://doi.org/10.1186/s12934-021-01583-6 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) application/pdf BMC Microbial Cell Factories 20 : Article number: 94 (2021) |
| spellingShingle | Vacuna Antígenos Genética Molecular Pichia pastoris Vaccines Rotavirus Antigens Molecular Genetics Dalvie, Neil C. Brady, Joseph R. Crowell, Laura E. Tracey, Mary Kate Biedermann, Andrew M. Kaur, Kawaljit Hickey, John M. Kristensen II, D. Lee Bonnyman, Alexandra D. Rodriguez-Aponte, Sergio A. Whittaker, Charles A. Bok, Marina Vega, Celina Guadalupe Mukhopadhyay, Tarit K. Joshi, Sangeeta B. Volkin, David B. Parreño, Gladys Love, Kerry R. Love, J. Christopher Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus |
| title | Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus |
| title_full | Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus |
| title_fullStr | Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus |
| title_full_unstemmed | Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus |
| title_short | Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus |
| title_sort | molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus |
| topic | Vacuna Antígenos Genética Molecular Pichia pastoris Vaccines Rotavirus Antigens Molecular Genetics |
| url | http://hdl.handle.net/20.500.12123/10760 https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-021-01583-6 https://doi.org/10.1186/s12934-021-01583-6 |
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