Rational design and optimization of downstream processes of virus particles for biopharmaceutical applications: Current advances

Vicente, Tiago; Mota, José P. B.; Peixoto, Cristina; Alves, Paula M.; Carrondo, Manuel J.T.

doi:10.1016/j.biotechadv.2011.07.004

Cited by 59 publications

(36 citation statements)

References 102 publications

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“…51 However, progresses are being made, and it is expected that in the near future the integration of process optimization tools (i.e., molecular biology, genetic engineering and systems biology), will overcome some of the current limitations affecting the large scale production of several types of VLPs. 144 VLPs can be produced in different expression systems, including bacterial, yeast, mammalian or plant cells. 51,[145][146][147] However, the most popular choice is expression in insect cells using the recombinant baculovirus technology.…”

Section: Challenges For Virus-like Particle-based Vaccine Developmentmentioning

confidence: 99%

Virus-like particle-based vaccines for animal viral infections

Crisci

Bárcena²,

Montoya

2013

Inmunología

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i n m u n o l o g í a . 2 0 1 3;3 2(3):102-116 103Por lo general son antigénicamente indistinguibles de los virus de los que proceden y su empleo como inmunógenos presenta importantes ventajas en términos de seguridad. Las VLPs pueden inducir una fuerte respuesta inmune, tanto humoral como celular, y se ha demostrado que poseen capacidad de actuar como adyuvantes (self-adjuvanting). Además de su idoneidad como vacunas frente al virus homólogo del cual proceden, las VLPs también se pueden utilizar como vectores para la presentación multimérica de antígenos heterólogos. Las VLPs han mostrado una elevada eficacia como candidatos vacunales, sin embargo, hasta el momento sólo una vacuna basada en VLPs ha sido autorizada y comercializada en el campo veterinario. En este trabajo se revisa el estado actual de las VLP empleadas como nuevas estrategias vacunales en el campo de la veterinaria, analizando las potenciales ventajas y desafíos que enfrenta esta tecnología.

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Section: Challenges For Virus-like Particle-based Vaccine Developmentmentioning

confidence: 99%

Virus-like particle-based vaccines for animal viral infections

Crisci

Bárcena²,

Montoya

2013

Inmunología

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“…In the past, the optimization of biological processes often relied on trial and error using a high number of experiments. With the additional use of mathematical methods, however, process design and optimization can be significantly accelerated (Mandenius & Brundin, 2008; Vicente, Mota, Peixoto, Alves, & Carrondo, 2011). In particular, decision‐making based on models is a more rational approach regarding critical factors and responses of the process under investigation.…”

Section: Introductionmentioning

confidence: 99%

A dynamic model linking cell growth to intracellular metabolism and extracellular by‐product accumulation

Ramos

Rath

Genzel

et al. 2020

Biotech & Bioengineering

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Mathematical modeling of animal cell growth and metabolism is essential for the understanding and improvement of the production of biopharmaceuticals. Models can explain the dynamic behavior of cell growth and product formation, support the identification of the most relevant parameters for process design, and significantly reduce the number of experiments to be performed for process optimization. Few dynamic models have been established that describe both extracellular and intracellular dynamics of growth and metabolism of animal cells. In this study, a model was developed, which comprises a set of 33 ordinary differential equations to describe batch cultivations of suspension AGE1.HN.AAT cells considered for the production of α1‐antitrypsin. This model combines a segregated cell growth model with a structured model of intracellular metabolism. Overall, it considers the viable cell concentration, mean cell diameter, viable cell volume, concentration of extracellular substrates, and intracellular concentrations of key metabolites from the central carbon metabolism. Furthermore, the release of metabolic by‐products such as lactate and ammonium was estimated directly from the intracellular reactions. Based on the same set of parameters, this model simulates well the dynamics of four independent batch cultivations. Analysis of the simulated intracellular rates revealed at least two distinct cellular physiological states. The first physiological state was characterized by a high glycolytic rate and high lactate production. Whereas the second state was characterized by efficient adenosine triphosphate production, a low glycolytic rate, and reactions of the TCA cycle running in the reverse direction from α‐ketoglutarate to citrate. Finally, we show possible applications of the model for cell line engineering and media optimization with two case studies.

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“…VLPs can be produced in a variety of cell culture systems including microbial (bacteria and yeasts, mainly Escherichia coli and Saccharomyces cerevisiae), insect (e.g., High Five™ cells from Trichoplusiani used in the Baculovirus Expression Vector System), mammalian (e.g., Chinese hamster ovary (CHO) cells) and -to a lesser extent-plant cells [16,17]. Therefore, both whole viruses and VLPs designed for vaccine formulations are derived from complex media containing biological impurities such as cell debris and host cell (HC)-derived contaminants (e.g., proteins, DNA, endotoxins), and their downstream processing must comply with strict purity requirements [13,14,20,21] detailed in regulatory guidelines [22]. Typical downstream production processes of viral particles involve three main steps (Fig.…”

Section: Viral Particle Purificationmentioning

confidence: 99%