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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
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dc.contributor.author | Dalvie, Neil C. | |
dc.contributor.author | Brady, Joseph R. | |
dc.contributor.author | Crowell, Laura E. | |
dc.contributor.author | Tracey, Mary Kate | |
dc.contributor.author | Biedermann, Andrew M. | |
dc.contributor.author | Kaur, Kawaljit | |
dc.contributor.author | Hickey, John M. | |
dc.contributor.author | Kristensen II, D. Lee | |
dc.contributor.author | Bonnyman, Alexandra D. | |
dc.contributor.author | Rodriguez-Aponte, Sergio A. | |
dc.contributor.author | Whittaker, Charles A. | |
dc.contributor.author | Bok, Marina | |
dc.contributor.author | Vega, Celina Guadalupe | |
dc.contributor.author | Mukhopadhyay, Tarit K. | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Volkin, David B. | |
dc.contributor.author | Parreño, Gladys | |
dc.contributor.author | Love, Kerry R. | |
dc.contributor.author | Love, J. Christopher | |
dc.date.accessioned | 2021-11-12T13:55:22Z | |
dc.date.available | 2021-11-12T13:55:22Z | |
dc.date.issued | 2021-05 | |
dc.identifier.issn | 1475-2859 | |
dc.identifier.other | https://doi.org/10.1186/s12934-021-01583-6 | |
dc.identifier.uri | http://hdl.handle.net/20.500.12123/10760 | |
dc.identifier.uri | https://microbialcellfactories.biomedcentral.com/articles/10.1186/s12934-021-01583-6 | |
dc.description.abstract | 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. | eng |
dc.format | application/pdf | es_AR |
dc.language.iso | eng | es_AR |
dc.publisher | BMC | es_AR |
dc.rights | info:eu-repo/semantics/openAccess | es_AR |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | |
dc.source | Microbial Cell Factories 20 : Article number: 94 (2021) | es_AR |
dc.subject | Vacuna | es_AR |
dc.subject | Vaccines | eng |
dc.subject | Rotavirus | eng |
dc.subject | Antígenos | es_AR |
dc.subject | Antigens | eng |
dc.subject | Genética Molecular | es_AR |
dc.subject | Molecular Genetics | eng |
dc.subject | Pichia pastoris | es_AR |
dc.title | Molecular engineering improves antigen quality and enables integrated manufacturing of a trivalent subunit vaccine candidate for rotavirus | es_AR |
dc.type | info:ar-repo/semantics/artículo | es_AR |
dc.type | info:eu-repo/semantics/article | es_AR |
dc.type | info:eu-repo/semantics/publishedVersion | es_AR |
dc.rights.license | Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) | |
dc.description.origen | Instituto de Virología | es_AR |
dc.description.fil | Fil: Dalvie, Neil C. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos | es_AR |
dc.description.fil | Fil: Dalvie, Neil C. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Brady, Joseph R. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos | es_AR |
dc.description.fil | Fil: Brady, Joseph R. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Crowell, Laura E. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos | es_AR |
dc.description.fil | Fil: Crowell, Laura E. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Tracey, Mary Kate. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Biedermann, Andrew M. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos | es_AR |
dc.description.fil | Fil: Biedermann, Andrew M. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Kaur, Kawaljit. University of Kansas. Vaccine Analytics and Formulation Center. Department of Pharmaceutical Chemistry; Estados Unidos | es_AR |
dc.description.fil | Fil: Hickey, John M. University of Kansas. Vaccine Analytics and Formulation Center. Department of Pharmaceutical Chemistry; Estados Unidos | es_AR |
dc.description.fil | Fil: Kristensen II, D. Lee. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Bonnyman, Alexandra D. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos | es_AR |
dc.description.fil | Fil: Bonnyman, Alexandra D. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Rodriguez-Aponte, Sergio A. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Rodriguez-Aponte, Sergio A. Massachusetts Institute of Technology. Department of Biological Engineering; Estados Unidos | es_AR |
dc.description.fil | Fil: Whittaker, Charles A. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Bok, Marina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina | es_AR |
dc.description.fil | Fil: Bok, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina | es_AR |
dc.description.fil | Fil: Vega, Celina Guadalupe. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina | es_AR |
dc.description.fil | Fil: Vega, Celina Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina | es_AR |
dc.description.fil | Fil: Mukhopadhyay, Tarit K. University College London. Department of Biochemical Engineering; Reino Unidos | es_AR |
dc.description.fil | Fil: Joshi, Sangeeta B. University of Kansas. Vaccine Analytics and Formulation Center. Department of Pharmaceutical Chemistry; Estados Unidos | es_AR |
dc.description.fil | Fil: Volkin, David B. University of Kansas. Vaccine Analytics and Formulation Center. Department of Pharmaceutical Chemistry; Estados Unidos | es_AR |
dc.description.fil | Fil: Parreño, Gladys Viviana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina | es_AR |
dc.description.fil | Fil: Parreño, Gladys Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina | es_AR |
dc.description.fil | Fil: Love, Kerry R. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos | es_AR |
dc.description.fil | Fil: Love, Kerry R. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.description.fil | Fil: Love, J. Christopher. Massachusetts Institute of Technology. Department of Chemical Engineering; Estados Unidos | es_AR |
dc.description.fil | Fil: Love, J. Christopher. Massachusetts Institute of Technology. The Koch Institute for Integrative Cancer Research; Estados Unidos | es_AR |
dc.subtype | cientifico |
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