An integrated and continuous downstream process for microbial virus-like particle vaccine biomanufacture.
Biotechnol Bioeng
; 119(8): 2122-2133, 2022 08.
Article
em En
| MEDLINE
| ID: mdl-35478403
ABSTRACT
In this study, we present the first integrated and continuous downstream process for the production of microbial virus-like particle vaccines. Modular murine polyomavirus major capsid VP1 with integrated J8 antigen was used as a model virus-like particle vaccine. The integrated continuous downstream process starts with crude cell lysate and consists of a flow-through chromatography step followed by periodic counter-current chromatography (PCC) (bind-elute) using salt-tolerant mixed-mode resin and subsequent in-line assembly. The automated process showed a robust behavior over different inlet feed concentrations ranging from 1.0 to 3.2 mg ml-1 with only minimal adjustments needed, and produced continuously high-quality virus-like particles, free of nucleic acids, with constant purity over extended periods of time. The average size remained constant between 44.8 ± 2.3 and 47.2 ± 2.9 nm comparable to literature. The process had an overall product recovery of 88.6% and a process productivity up to 2.56 mg h-1 mlresin-1 in the PCC step, depending on the inlet concentration. Integrating a flow through step with a subsequent PCC step allowed streamlined processing, showing a possible continuous pathway for a wide range of products of interest.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vacinas de Partículas Semelhantes a Vírus
Limite:
Animals
Idioma:
En
Revista:
Biotechnol Bioeng
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Austrália