Flow virometry for process monitoring of live virus vaccines-lessons learned from ERVEBO.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
01 04 2021
01 04 2021
Historique:
received:
23
06
2020
accepted:
04
03
2021
entrez:
2
4
2021
pubmed:
3
4
2021
medline:
23
11
2021
Statut:
epublish
Résumé
Direct at line monitoring of live virus particles in commercial manufacturing of vaccines is challenging due to their small size. Detection of malformed or damaged virions with reduced potency is rate-limited by release potency assays with long turnaround times. Thus, preempting batch failures caused by out of specification potency results is almost impossible. Much needed are in-process tools that can monitor and detect compromised viral particles in live-virus vaccines (LVVs) manufacturing based on changes in their biophysical properties to provide timely measures to rectify process stresses leading to such damage. Using ERVEBO, MSD's Ebola virus vaccine as an example, here we describe a flow virometry assay that can quickly detect damaged virus particles and provide mechanistic insight into process parameters contributing to the damage. Furthermore, we describe a 24-h high throughput infectivity assay that can be used to correlate damaged particles directly to loss in viral infectivity (potency) in-process. Collectively, we provide a set of innovative tools to enable rapid process development, process monitoring, and control strategy implementation in large scale LVV manufacturing.
Identifiants
pubmed: 33795759
doi: 10.1038/s41598-021-86688-z
pii: 10.1038/s41598-021-86688-z
pmc: PMC8016999
doi:
Substances chimiques
Ebola Vaccines
0
Vaccines, Attenuated
0
Vaccines, Synthetic
0
Viral Vaccines
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
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