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Multi-attribute monitoring (MAM) methodology for glycosylated subunit vaccines

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Publicado en:Scientific Reports (Nature Publisher Group) vol. 15, no. 1 (2025), p. 41198-41215
Autor principal: Shajahan, Asif
Otros Autores: Jenkins, Lisa M., Barefoot, Nathan, Maldonado, Darielys, Wolff, Jeremy J., Yang, Yanhong, Kueltzo, Lisa A., Ficca, Valerie, Scheideman, Elizabeth, Loukinov, Ivan, Carruthers, Carl, Benmohamed, Dorra, Gowetski, Daniel B., Jiang, Rong, Yang, Sylvie R., Carlton, Kevin, Gall, Jason G., Lei, Q. Paula
Publicado:
Nature Publishing Group
Materias:
Monoclonal antibodies
Dihydrofolate reductase
Software
Vaccines
Cell culture
Post-translation
Glycoproteins
Amino acid sequence
Data processing
Scientific imaging
Chromatography
Immune system
Peptides
Monitoring
Drug development
Proteins
Mass spectrometry
Human immunodeficiency virus > HIV
Glycosylation
Vaccine development
Heterogeneity
Oxidation
Process controls
Product development
Environmental
Acceso en línea:Citation/Abstract
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Resumen:Many protein-based vaccines comprise viral surface proteins which are chosen for their ability to stimulate the immune system. These vaccine molecules are often heavily glycosylated, and glycosylation plays critical roles in the immunological and stability properties of vaccines. The structural characterization and product quality attribute monitoring of such complex vaccine therapeutics during process development and manufacturing is very challenging. High throughput monitoring of multiple molecular attributes, particularly glycosylation, of recombinant glycoprotein subunit vaccines are needed to support entire vaccine production processes. Multi-attribute monitoring (MAM) technology involves assessing multiple critical molecular attributes of molecules in one set of analyses in an automated fashion, for product quality attribute requirements. MAM is still in the early development stages and is currently applied to therapeutics with very low levels of glycosylation such as monoclonal antibodies. MAM on glycoproteins with a higher number of glycosylation sites with high glycan heterogeneity such as subunit vaccine molecules is challenging as each glycan site and glycan modification exponentially increases data processing complexity. We developed a MAM workflow to perform detailed structural characterization of subunit protein vaccines, monitoring critical parameters such as intact mass, sequence identity, protein clipping, glycosylation, other post-translational modifications, and host cell proteins (HCP). By using a combination of software tools and product process monitoring strategy, we performed data processing at multiple steps and identified key attributes for each vaccine candidate under the development pipeline. Further, a high-throughput critical attribute monitoring MAM workflow was developed to support the influenza and HIV vaccine development processes including cell line selection, cell clone selection, cell culture optimization, stability study evaluation and final vaccine product characterization.
ISSN:2045-2322
DOI:10.1038/s41598-025-24922-8
Fuente:Science Database