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Ali A.,National Institute for Biotechnology and Genetic Engineering NIBGE | An S.J.,Korean International Vaccine Institute | Cui C.,Korean International Vaccine Institute | Cui C.,Chengdu Institute of Biological Products | And 2 more authors.
Human Vaccines and Immunotherapeutics | Year: 2014

Salmonella enterica serovar Paratyphi A (S. Paratyphi A) is a human restricted pathogen that can cause systemic infection (paratyphoid fever) with recently increased incidence particularly in developing countries. Currently there is no licensed vaccine for prevention of infection from S. Paratyphi A. In this study the O-specific polysaccharide (OSP) of S. Paratyphi A was conjugated to diphtheria toxoid (DT) with and without adipic acid dihydrazide (ADH) as a linker. Binding of the OSP to a carrier protein was intended to convert a T-cell independent OSP response to a T-cell dependent response inducing higher levels of anti-OSP antibodies and immunological memory. These conjugates (OSP-AH-DT and OSP-DT) were evaluated for their immunogenicity in mice. The S. Paratyphi A OSP-DT conjugate induced a poor anti-OSP response less than that observed with LPS while the OSP-AH-DT conjugate induced a significantly higher antibody titer compared with LPS alone. The study also demonstrated diphtheria toxoid as a potential carrier protein for conjugate vaccine candidates using S. Paratyphi A OSP. © 2014 Landes Bioscience.

Yao G.,Chengdu Institute of Biological Products | Li Y.,University of Sichuan
Biomedicine and Preventive Nutrition | Year: 2011

Ligusticum chuanxiong oil is a kind of volatile oil from rhizome of ligusticum Chuanxiong (VOC). It is pharmacologically active in treating a variety of diseases. However, the instability and poor water solubility have limited its further clinical application. In the present study, a self-microemulsifying drug delivery system (SMEDDS) was developed and SMEDDS based formulation - VOC-SMEDDS capsules were prepared to improve the water solubility of Ligusticum chuanxiong oil as well as to enhance VOC oral absorption. The VOC microemulsions were composed of chuanxiong oil, Tween-80 and propylene glycol at the optimized ratio of 0.6:0.32:0.08 (w/w), the average size of which was less than 50. nm upon dilution with water, and the particles of which were observed round-shaped under microscopy. The solubility study indicated that up to 90% of VOC-SMEDDS capsules dissolved in 20. minutes. The stability test showed the VOC-SMEDDS capsules maintained stable in 6 months. In situ absorption study demonstrated the absorption rate of VOC-SMEDDS capsules was 2.53 and 1.59 times higher than that of VOC and VOC/β-Cyclodextrin inclusion (β-CD), and the percent absorption (PA) of which was 1.55 and 28.19 times higher than that of VOC and VOC/β-CD, respectively. © 2011 Elsevier Masson SAS.

Duan W.,CAS Institute of Biophysics | Duan W.,University of Chinese Academy of Sciences | Zhou J.,CAS Institute of Biophysics | Zhou J.,Chengdu Institute of Biological Products | And 9 more authors.
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2011

The binding of lipopolysaccharides (LPS) to macrophages results in inflammatory responses. In extreme cases it can lead to endotoxic shock, often resulting in death. A broad range of antioxidants, including tocopherols, can reduce LPS activity in vitro and in vivo. To elucidate the underlying mechanisms of their action, we investigated the effect of the sodium salt of γ-L-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-1-benzopyran-6-yl]oxy]carbonyl]-3-[[2-(1H-indol-3-yl)ethyl]amino]-3-oxopropyl]-L-cysteinylglycine (ESeroS-GS), a novel α-tocopherol derivative, on LPS-induced inflammation in vitro and in vivo. ESeroS-GS reduced the transcription of TNF-α, IL-1β, IL-6 and iNOS genes in a dose-dependent manner in RAW264.7 macrophages, and inhibited the release of these inflammatory factors. In addition, ESeroS-GS inhibited LPS-induced mortality in a mouse sepsis model. Electrophoretic mobility shift assays (EMSA) and reporter gene assays revealed that ESeroS-GS down-regulated the transcriptional activity of NF-κB. By analyzing the partitioning of CD14 and Toll-like receptor 4 (TLR-4) in cell membrane microdomains, we found that ESeroS-GS attenuates the binding of LPS to RAW264.7 cells via interfering with the relocation of CD14 and TLR-4 to lipid rafts, blocking the activation of interleukin-1 receptor-associated kinase 1 (IRAK-1), and inhibiting the consequent phosphorylation of TAK1 and IKKα/β, which together account for the suppression of NF-κB activation. Taken together, our data suggest that ESeroS-GS can modulate LPS signaling in macrophages by impairing TLR-4 complex assembly via a lipid raft dependent mechanism. This article is part of a Special Issue entitled: 11th European Symposium on Calcium. © 2011 Elsevier B.V.

Markey K.,UK National Institute for Biological Standards and Control | Ho M.M.,UK National Institute for Biological Standards and Control | Choudhury B.,UK National Institute for Biological Standards and Control | Seki M.,Japan BCG Laboratory | And 7 more authors.
Vaccine | Year: 2010

Current methods for the identification of BCG vaccine in quality control settings involve acid-fast staining with microscopic examination. However, this method is unable to distinguish the many different sub-strains of BCG, or to differentiate BCG strains from virulent members of the Mycobacterium tuberculosis complex. A multiplex PCR (mPCR) which uses six target regions in mycobacteria has been developed to identify specific sub-strains of BCG. This study reports the findings from an international collaborative study to assess the accuracy, robustness and reproducibility of this mPCR method to differentiate BCG sub-strains. The method was found to fulfil these criteria successfully and was able to distinguish BCG sub-strains in vaccine preparations. The majority of the participants in the study generated the expected PCR product profiles indicating the method is also robust. © 2010 Elsevier Ltd.

Wijesinghe P.R.,Epidemiological Unit | Abeysinghe M.R.N.,Epidemiological Unit | Yoksan S.,Mahidol University | Yao Y.,Chengdu Institute of Biological Products | And 5 more authors.
Vaccine | Year: 2014

Introduction: To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine at 9 months of age. Serum immune responses were evaluated post-vaccination on days 28, 180, and 365 using JE neutralization test and anti-measles IgG ELISA. Results: 278 infants received one dose of LJEV and measles vaccine. Of these, 257 were eligible for the per-protocol analysis. On Day 0, 14 infants (5.5%) were seropositive for JE, but none were seropositive for measles. At Day 28, seropositivity rates were 90.7% (95% CI, 86.4-93.9%) for JE and 84.8% (95% CI, 79.8-89.0%) for measles. The geometric mean titer for JE neutralizing antibodies was 111 (95% CI, 90-135), and the geometric mean concentration (GMC) for anti-measles IgG was 375. mIU/mL (95% CI, 351-400. mIU/mL). Over the next year, JE neutralizing antibody responses declined only slightly, with seropositivity at 87.4% (95% CI, 82.6-91.2%) at Day 365. In contrast, measles antibody levels continued to increase over time. Seropositivity for anti-measles IgG reached 97.2% (95% CI, 94.4-98.9%) at Day 365, and the GMC rose to 1202. mIU/mL (95% CI, 1077-1341. mIU/mL). Co-administration of LJEV and measles vaccine was also safe. Most adverse reactions were mild, and no serious adverse events were related to study vaccinations. Conclusion: The safety and immunogenicity of LJEV co-administered with measles vaccine in Sri Lankan infants is similar to that seen in other populations, and our results support use of LJEV at 9 months of age. Live SA 14-14-2 vaccine is now prequalified by the WHO for use in infants in Asia, and other countries may wish to introduce LJEV to combat this devastating disease. © 2014 The Authors.

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