Shanghai Institute of Biological Products

Shanghai, China

Shanghai Institute of Biological Products

Shanghai, China
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Yan M.-N.,Shanghai JiaoTong University | Dai K.-R.,Shanghai JiaoTong University | Tang T.-T.,Shanghai JiaoTong University | Zhu Z.-A.,Shanghai JiaoTong University | Lou J.-R.,Shanghai Institute of Biological Products
Journal of Biomedical Materials Research - Part A | Year: 2010

Impaction bone allografting represents an attractive procedure for bone defects reconstruction in joint replacement. And it was found that bone morphogenetic protein-2(BMP-2) gene therapy can enhance bone healing. The purpose of this study was to determine if combined adenovirus mediated human BMP-2(Adv-hBMP-2) gene-modified bone marrow stromal cells(BMSCs) with allograft enhanced the defects healing and improved the strength of implant fixation in 3-mm bone defect around a titanium alloy implant. Using the impaction grafting technique, the defects were reconstructed using freeze-dried allograft, freeze-dried allografts loaded with autogenous BMSCs, or freeze-dried allografts loaded with autogenous BMSCs modified with the human bone morphogenetic protein-2 (hBMP-2) gene. At 6 and 12 weeks, the Bone-implant Contact rate and strength of the interface in the group with BMP-2 gene medication were significantly higher than those of the non-cell or cell groups. BMP-2 gene medication also showed significant effects on allograft healing and replacement compared with those of two other groups, as evidenced by increased new bone formation and reduced graft remnants. The results suggest that BMP-2 gene medication can enhance allograft healing and osseointegration of the bone-implant interface. © 2009 Wiley Periodicals, Inc.


He C.,Shanghai JiaoTong University | He C.,Shanghai Institute of Biological Products | Yang Z.,Shanghai JiaoTong University | Yang Z.,Shanghai Institute of Biological Products | And 2 more authors.
Journal of Chromatography A | Year: 2011

A downstream processing was examined for Vero cell-derived human influenza virus (H1N1) grown in serum free medium. Vero cell banks were established in serum free medium and characterized according to regulatory requirements. Serum free Vero cells were grown on Cytodex 3 microcarriers in 5. L bioreactor and infected with influenza A virus (A/New Caledonia/99/55). The harvests were processed with the sequence of inactivation, clarification, anion exchange chromatography (DEAE FF), Cellufine Sulfate Chromatography (CSC) and size exclusion chromatography (Sepharose 6FF). Host cell DNA (hcDNA) was mainly removed with DEAE FF column and CSC by 40 and 223 fold, respectively. Most of Vero cell proteins were eliminated in CSC and Sepharose 6FF unit operation by about 13 fold. The overall scheme resulted in high recovery of hemagglutinin (HA) activity and the substantial removal of total protein, host protein and DNA. The total protein content and DNA content per 15 μg HA protein in final product was 89 μg and 33. pg, respectively, which complied with regulatory requirements for single strain influenza vaccines. SDS-PAGE analysis and Western blotting confirmed the purity of the final product. In conclusion, the suggested downstream process is suitable for the purification of microcarrier-based cell-derived influenza vaccine. © 2011 Elsevier B.V.


Sui Z.,CAS Wuhan Institute of Virology | Sui Z.,University of Chinese Academy of Sciences | Chen Q.,CAS Wuhan Institute of Virology | Fang F.,Hunan Normal University | And 4 more authors.
Vaccine | Year: 2010

The antigenic variation of influenza virus represents a major health problem, thus continuous efforts have been made to develop broad-spectrum vaccines against influenza virus. Matrix protein 1 (M1) protein is highly conserved in all influenza A strains. In this study, M1 protein was efficiently expressed in Escherichia coli (E. coli), then purified and used for immunization of BALB/c mice by intranasal drip using chitosan as adjuvant. The M1 protein was administered intranasally to mice in combination with chitosan adjuvant twice at an interval of 3 weeks. Three weeks after the second immunization, the mice were challenged with a lethal dose (5×LD50) of A/Chicken/Jiangsu/7/2002 (H9N2) virus, PR8 (H1N1) virus and A/Chicken/Henan/12/2004 (H5N1) virus. The protective immunity of the vaccine was evaluated by determining the survival rates, residual lung virus titers, bodyweight, and the serum antibody titers of the mice. The results showed that nasal administration of 100μg M1 in combination with chitosan could not only completely protect the mice effectively against the challenge of the homologous virus but also protect 70% and 30% of the mice against the heterologous H1N1 and H5N1 viruses, respectively. The study indicated that the M1 protein was a candidate antigen for a broad-spectrum influenza virus vaccine and the adjuvant chitosan significantly improved the efficacy of the M1 vaccine. © 2010 Elsevier Ltd.


Zhang H.,CAS Wuhan Institute of Virology | Zhang H.,University of Chinese Academy of Sciences | Chen Q.,CAS Wuhan Institute of Virology | Chen Z.,CAS Wuhan Institute of Virology | And 2 more authors.
Virus Genes | Year: 2012

In January 2009, an H4N2 subtype of avian influenza virus [A/duck/Hunan/8-19/2009 (H4N2)] was isolated from domestic ducks in Dongting Lake wetland. The whole genome of the virus was sequenced and the results indicated that multiple gene segments of the virus had a high homology with viruses isolated from wild waterfowl, which indicated that the virus was probably transmitted from wild waterfowl to domestic ducks. Phylogenetic analysis revealed that the each gene belonged to the Eurasian lineage of avian influenza viruses, but genetic reassortment occurs between viruses of different subtypes. © Springer Science+Business Media, LLC 2011.


Zheng D.,Shanghai Institute of Biological Products | Yi Y.,Shanghai Institute of Biological Products | Chen Z.,Shanghai Institute of Biological Products | Chen Z.,Hunan Normal University
Viruses | Year: 2012

Several global outbreaks of highly pathogenic avian influenza (HPAI) H5N1 virus have increased the urgency of developing effective and safe vaccines against H5N1. Compared with H5N1 inactivated vaccines used widely, H5N1 live-attenuated influenza vaccines (LAIVs) have advantages in vaccine efficacy, dose-saving formula, long-lasting effect, ease of administration and some cross-protective immunity. Furthermore, H5N1 LAIVs induce both humoral and cellular immune responses, especially including improved IgA production at the mucosa. The current trend of H5N1 LAIVs development is toward cold-adapted, temperature-sensitive or replication-defective vaccines, and moreover, H5N1 LAIVs plus mucosal adjuvants are promising candidates. This review provides an update on the advantages and development of H5N1 live-attenuated influenza vaccines. © 2012 by the authors; licensee MDPI, Basel, Switzerland.


Zheng M.,Shanghai Institute of Biological Products | Luo J.,Shanghai Institute of Biological Products | Chen Z.,Shanghai Institute of Biological Products | Chen Z.,CAS Wuhan Institute of Virology | Chen Z.,Hunan Normal University
Infection | Year: 2014

Purpose: Vaccination is the safest and most effective measure against influenza virus infections. However, traditional influenza vaccines cannot respond effectively to an unforeseen epidemic or pandemic caused by a virus with antigenic drifts or antigenic shifts. Therefore, developing a universal influenza vaccine (UIV) that induces broad-spectrum and long-term immunity has become a major trend in influenza vaccine research and development. Methods: This article reviews the development of UIVs based on these conserved influenza virus proteins. Results and Conclusion: The matrix protein (M1, M2) and nucleoprotein (NP) of influenza viruses have highly conserved sequences, and they become the major target antigens of current UIV studies. © 2013 Springer-Verlag.


Chen Q.,CAS Wuhan Institute of Virology | Huang S.,CAS Wuhan Institute of Virology | Chen J.,CAS Wuhan Institute of Virology | Zhang S.,CAS Wuhan Institute of Virology | And 3 more authors.
PLoS ONE | Year: 2013

Two surface glycoproteins of influenza virus, haemagglutinin (HA) and neuraminidase (NA), play opposite roles in terms of their interaction with host sialic acid receptors. HA attaches to sialic acid on host cell surface receptors to initiate virus infection while NA removes these sialic acids to facilitate release of progeny virions. This functional opposition requires a balance. To explore what might happen when NA of an influenza virus was replaced by one from another isolate or subtype, in this study, we generated three recombinant influenza A viruses in the background of A/PR/8/34 (PR8) (H1N1) and with NA genes obtained respectively from the 2009 pandemic H1N1 virus, a highly pathogenic avian H5N1 virus, and a lowly pathogenic avian H9N2 virus. These recombinant viruses, rPR8-H1N1NA, rPR8-H5N1NA, and rPR8-H9N2NA, were shown to have similar growth kinetics in cells and pathogenicity in mice. However, much more rPR8-H5N1NA and PR8-wt virions were released from chicken erythrocytes than virions of rPR8-H1N1NA and rPR8-H9N2NA after 1 h. In addition, in MDCK cells, rPR8-H5N1NA and rPR8-H9N2NA infected a higher percentage of cells, and induced cell-cell fusion faster and more extensively than PR8-wt and rPR8-H1N1NA did in the early phase of infection. In conclusion, NA replacement in this study did not affect virus replication kinetics but had different effects on infection initiation, virus release and fusion of infected cells. These phenomena might be partially due to NA proteins' different specificity to α2-3/2-6-sialylated carbohydrate chains, but the exact mechanism remains to be explored. © 2013 Chen et al.


Chen J.,CAS Wuhan Institute of Virology | Chen J.,University of Chinese Academy of Sciences | Huang S.,CAS Wuhan Institute of Virology | Huang S.,University of Chinese Academy of Sciences | And 3 more authors.
Journal of General Virology | Year: 2010

The non-structural protein NS2, also called nuclear export protein, of influenza A virus contains a leucine-rich nuclear-export signal that could guide viral ribonucleoproteins to cross the nuclear pore complex (NPC) and complete directional nucleocytoplasmic trafficking. In this study, human nucleoporin 98 (hNup98), an NPC protein, was identified as an NS2-binding protein by using yeast two-hybrid screening of a human cDNA library. Interaction between NS2 and hNup98 was confirmed in yeast and mammalian cells. Mapping tests further demonstrated that aa 22-53 in the N-terminal region of NS2 and the glycine-leucine-phenylalanine-glycine (GLFG) repeat domain (aa 1-511) of hNup98 are crucial for the interaction of these two proteins. Confocal microscopy showed that hNup98 could specifically recruit NS2 to the nucleoli and that this process was inhibited by leptomycin B, a specific inhibitor of human chromosomal region maintenance 1 protein. NS2 recruitment to the nucleoli was through the N-terminal GLFG repeat domain of hNup98, but not through the C-terminal domain. Moreover, influenza virus infection downregulated Nup98 levels significantly in 293T and Madin-Darby canine kidney cells. Overexpression of the GLFG repeat domain of hNup98 apparently inhibited virus propagation. Together, these findings reveal the interaction between hNup98 and NS2. The GLFG repeat domain of hNup98 might competitively inhibit the interaction between NS2 and endogenous hNup98, consequently inhibiting virus propagation. © 2010 SGM.


Fan X.,National Institutes for Food and Drug Control | Fan X.,PLA Fourth Military Medical University | Hashem A.M.,Biologics | Hashem A.M.,King Abdulaziz University | And 14 more authors.
Mucosal Immunology | Year: 2015

The influenza viral hemagglutinin (HA) is comprised of two subunits. Current influenza vaccine predominantly induces neutralizing antibodies (Abs) against the HA1 subunit, which is constantly evolving in unpredictable fashion. The other subunit, HA2, however, is highly conserved but largely shielded by the HA head domain. Thus, enhancing immune response against HA2 could potentially elicit broadly inhibitory Abs. We generated a recombinant adenovirus (rAd) encoding secreted fusion protein, consisting of codon-optimized HA2 subunit of influenza A/California/7/2009(H1N1) virus fused to a trimerized form of murine CD40L, and determined its ability of inducing protective immunity upon intranasal administration. We found that mice immunized with this recombinant viral vaccine were completely protected against lethal challenge with divergent influenza A virus subtypes including H1N1, H3N2, and H9N2. Codon-optimization of HA2 as well as the use of CD40L as a targeting ligand/molecular adjuvant were indispensable to enhance HA2-specific mucosal IgA and serum IgG levels. Moreover, induction of HA2-specific T-cell responses was dependent on CD40L, as rAd secreting HA2 subunit without CD40L failed to induce any significant levels of T-cell cytokines. Finally, sera obtained from immunized mice were capable of inhibiting 13 subtypes of influenza A viruses in vitro. These results provide proof of concept for a prototype HA2-based universal influenza vaccine.


Jiang Z.,Shanghai Institute of Biological Products | Tong G.,Shanghai Institute of Biological Products | Cai B.,Shanghai Institute of Biological Products | Xu Y.,Shanghai Institute of Biological Products | Lou J.,Shanghai Institute of Biological Products
Protein Expression and Purification | Year: 2011

Two human papillomavirus (HPV) prophylactic vaccines are currently available in the market: Gardasil and Cervarix. These two vaccines work against tumor high-risk subtypes HPV 16 and HPV 18. However, they do not include other high-risk subtypes such as HPV 58. Epidemiological research in China shows that HPV 58 is a prevalent high-risk subtype, second only to HPV 16 and HPV 18. Thus, for cervical cancer prevention in China, developing a vaccine against HPV 58 is necessary. In this study, HPV 58 virus-like particles (VLPs) were expressed in the Pichia pastoris, and subsequently purified through pretreatment and a three-step purification process consisting of strong cation exchange chromatography, size-exclusion chromatography, and hydroxyapatite chromatography. The highly purified HPV 58 VLPs were confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis, electron microscopy, dynamic laser scattering, and ultracentrifugation. The purified VLPs were used to immunize mice to test their ability to induce humoral immunity. Enzyme-linked immunosorbent assays were performed on the sera of the immunized mice and significantly high anti-HPV 58 VLP antibody titers were observed. The immunogenicity study demonstrates that the purified HPV 58 VLPs are HPV vaccine candidates. © 2011 Elsevier Inc. All rights reserved.

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