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Huang D.,East China University of Science and Technology | Xia-Hou K.,East China University of Science and Technology | Liu X.-P.,East China University of Science and Technology | Zhao L.,East China University of Science and Technology | And 5 more authors.
Vaccine | Year: 2014

Influenza vaccine production using cell culture technology has become popular nowadays. However, to meet the ever increasing demand of influenza vaccine, it is prerequisite to improve the yield of influenza virus in cells. To achieve this, in the present study, the nutritional requirements of MDCK cells in the virus production process were analyzed and a nutrient-feeding strategy was developed accordingly. Based on the consumption rates and corresponding concentration optimization, glucose and fast metabolized amino acids were supplemented into the maintaining medium at the time of infection. Compared with the non-supplemented culture, the average cell specific death rate during 0-48h post-infection was 0.013h-1, which was 40.91% lower in the nutrient-supplemented culture. Total virus titer, HA antigen protein concentration and cell-specific virus yield were (1.88±0.23)×103HAunits/50μL, 11.70±0.22μg/mL and (10.06±1.16)×103virions/cell, respectively, which were 84.04±22.50%, 31.46±2.87% and 86.64±25.81% higher than those in the control, respectively. These data showed that the appropriate supplementation of nutrients during virus production process could reduce cell death, and improve cell-specific virus yield and total influenza virus output. This study laid foundation for the development of cell culture technology for influenza vaccine production. © 2014 Elsevier Ltd. Source


Wu G.-P.,Shanghai Institute of Biological Products Co. | Zhu W.,Shanghai Institute of Biological Products Co.
Chinese Journal of Biologicals | Year: 2016

Varicella-zoster virus (VZV) is the pathogen of varicella (chicken pox) and herpes zoster (shingles,HZ), with a high infectivity and morbidity. VZV-Oka strain is the only strain used for vaccine production recommended by the WHO. The effectiveness and safety of varicella vaccine have been confirmed in post-marketing application. Meanwhile, HZ vaccines are under development by many pharmaceutical companies. This paper reviews the epidemiology of VZV and development of vaccines. Source


Liu X.-P.,East China University of Science and Technology | Huang D.,East China University of Science and Technology | Tan W.-S.,East China University of Science and Technology | Luo J.,Shanghai Institute of Biological Products Co. | Chen Z.,Shanghai Institute of Biological Products Co.
Human Vaccines and Immunotherapeutics | Year: 2015

Metabolic analysis for medium optimization represents a very useful strategy in the process development of production of vaccines in cells. During influenza vaccine production, viruses hijack host cells and take advantage of host's metabolism. As a consequence, the nutritional demand of host cells should undergo a profound change, and usually more nutrients such as glucose and amino acids should be consumed. As such, the maintaining media used in virus production processes often cannot provide sufficient nutrients, and novel methods are urged to be established to address this severe issue of nutritional limitation. A detailed study on impacts of influenza virus on cell death and metabolism, with a profound analysis of nutritional requirements during virus production process, followed by a rational medium optimization is expected to be the most straightfoward and effective strategy. This would ensure a balanced and adequate nutritional supply, which should minimize cell death and improve both cell-specific virus yield and total influenza virus production. Such a metabolic analysis-based medium optimization would lay a solid foundation for the development of cell culture technology in influenza vaccine production. © 2015, Taylor & Francis Group, LLC. Source


Yin L.,Fudan University | Yin L.,University of Illinois at Urbana - Champaign | Zhao X.,Fudan University | Zhao X.,Shanghai Institute of Biological Products Co. | And 7 more authors.
Biomaterials | Year: 2014

Hypertrophic scar (HS) originates from the over-expression of transforming growth factor β (TGF-β) and downstream SMAD2. With attempts to rectify HS by RNA interference (RNAi) against SMAD2, we report the design of plasmid DNA encoding SMAD2 siRNA (pSUPER-SMAD2), and identify the optimal siRNA sequence toward maximal RNAi efficiency. To realize effective and sustained RNAi, we developed gene activated matrix (GAM) based on porous atelocollagen scaffold and embedded trimethyl chitosan-cysteine (TMCC)/pSUPER-SMAD2 polyplexes for promoting cell growth and gene transfection. The GAM exhibited porosity higher than 80%, pore size of 200-250μm, desired mechanical strength, and sustained pSUPER-SMAD2 release profiles. Normal skin fibroblasts (NSFs) and hypertrophic scar fibroblasts (HSFs) were allowed to infiltrate and proliferate in GAM; at the meantime they were transfected with TMCC/pSUPER-SMAD2 polyplexes to display remarkably reduced SMAD2 levels that lasted for up to 10 days, consequently inhibiting the over-production of type I and type III collagen. We further unraveled the notably higher transfection levels of GAM in three-dimensional (3D) than in 2D environment, which was attributed to the improved cell-matrix interactions that promote cell proliferation and polyplex internalization. This highly safe and effective GAM may serve as a promising candidate towards HS treatment. © 2013 Elsevier Ltd. Source


Liu Z.-Y.,Shanghai Institute of Biological Products Co. | Meng J.-F.,Shanghai Institute of Biological Products Co. | Cheng P.-F.,Shanghai Institute of Biological Products Co.
Chinese Journal of Biologicals | Year: 2013

Single-radial immunodiffusion (SRID) test is the most common method tor determination ot hemagglutinin (HA) content in influenza vaccine. In order to solve the problem that reference reagents are inavailable at early stage of outbreak of pandemic influenza and to increase the sensitivity, reproducibility and accuracy of test method, alternative physical-chemical and immunochemical methods are investigated. This paper reviews the progress in research on methods for determination of HA in influenza vaccine in the last decade. Source

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