Accelerating vaccine manufacturing development through model-based approaches: current advances and future opportunities

This review highlights the importance of model-based&nbsp;approaches in accelerating vaccine manufacturing process development. The challenges of scaling up from laboratory to&nbsp;commercial processes are addressed through the adoption of Process Analytical Technology frameworks and Quality by&nbsp;Design principles. The application of various modeling approaches beyond downstream and upstream processes in&nbsp;vaccine production is discussed in detail. These in silico process simulation approaches enable deeper understanding&nbsp;of manufacturing dynamics, identification of critical process parameters, and the development of well-defined design&nbsp;spaces, ultimately leading to accelerated vaccine development and improved product quality. The authors stress the&nbsp;significance of an integrated modeling platform for vaccine manufacturing, exemplified by the Inno4Vac project. This&nbsp;initiative seeks to develop a comprehensive computational platform for vaccine manufacturing and stability testing, with a&nbsp;particular focus on stakeholder engagement and collaboration with regulatory bodies to ensure the acceptance and&nbsp;implementation of the&nbsp;platform.</p

Diet-dependent function of the extracellular matrix proteoglycan Lumican in obesity and glucose homeostasis.

Objective: Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications.Methods: Whole body ablation of Lumican (Lum(-/-)) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling.Results: Lumican was found to be particularly enriched in the stromal cells isolated from murine gonadal white adipose tissue. Likewise murine and human visceral fat showed a robust increase in Lumican as compared to fat from the subcutaneous depot. Lumican null female mice exhibited moderately increased fat mass, decreased insulin sensitivity and increased liver triglycerides in a diet-dependent manner. These changes coincided with inflammation in adipose tissue and no overt effects in adipose expandability, i.e. adipocyte formation and hypertrophy. Lumican over-expression in visceral fat and liver resulted in improved insulin sensitivity and glucose clearance.Conclusions: These data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome. (C) 2018 The Authors. Published by Elsevier GmbH