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ABSTRACT: Antigen specific memory T cells (Tm) have been demonstrated to be an important factor in protecting hosts against subsequent infection by previously encountered pathogens. During T-cell activation, several cytokines including IL-6, IL-7 and IL-15 play crucial roles in the development of T cells into memory cells T cells. With the aim of generating specific Tm, we examined a strategy of sequential administration of molecular adjuvants, in which a DNA vaccine encoding the VP1 capsid protein of foot and mouth disease virus (designated pcD-VP1) was co-delivered to mice along with an IL-6 expressing plasmid (pVAX-IL-6) as an initial molecular adjuvant and boosted with either an IL-7 or IL-15 expressing plasmid, (pVAX-IL-7 or proVAX-IL-15) as the secondary adjuvant. During the pcD-VP1 immunization, we demonstrated that the groups primed with IL-6 and boosted with either IL-7 or IL-15 resulted in the enhancement of cellular and humoral immune responses, maturation of dendritic cells (DCs) and macrophages, and importantly, a higher frequency of CD4 (+) Tm, characterized by expressing CD44 (high) CD62L (low) markers, compared with the other groups. Thus, we take advantages of the different effects of cytokines on T cell development to induce not only higher level of immune responses after vaccination, but also to generate a higher ratio of CD4 (+) Tm in this sequential cytokine prime-boost study. This then would lead to the mounting of an effective long-term antigen specific immune response.
Human vaccines & immunotherapeutics. 11/2012; 8(11).
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Yuan Yuan,
Lipu Song,
Minhui Li,
Guiming Liu,
Yanan Chu,
Luyu Ma,
Yuanyuan Zhou, Xiao Wang,
Wei Gao,
Shuangshuang Qin,
Jun Yu,
Xumin Wang,
Luqi Huang
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ABSTRACT: Traditional Chinese medicine uses various herbs for the treatment of various diseases for thousands of years and it is now time to assess the characteristics and effectiveness of these medicinal plants based on modern genetic and molecular tools. The herb Flos Lonicerae Japonicae (FLJ or Lonicera japonica Thunb.) is used as an anti-inflammatory agent but the chemical quality of FLJ and its medicinal efficacy has not been consistent. Here, we analyzed the transcriptomes and metabolic pathways to evaluate the active medicinal compounds in FLJ and hope that this approach can be used for a variety of medicinal herbs in the future.
We assess transcriptomic differences between FLJ and L. japonica Thunb. var. chinensis (Watts) (rFLJ), which may explain the variable medicinal effects. We acquired transcriptomic data (over 100 million reads) from the two herbs, using RNA-seq method and the Illumina GAII platform. The transcriptomic profiles contain over 6,000 expressed sequence tags (ESTs) for each of the three flower development stages from FLJ, as well as comparable amount of ESTs from the rFLJ flower bud. To elucidate enzymatic divergence on biosynthetic pathways between the two varieties, we correlated genes and their expression profiles to known metabolic activities involving the relevant active compounds, including phenolic acids, flavonoids, terpenoids, and fatty acids. We also analyzed the diversification of genes that process the active compounds to distinguish orthologs and paralogs together with the pathways concerning biosynthesis of phenolic acid and its connections with other related pathways.
Our study provides both an initial description of gene expression profiles in flowers of FLJ and its counterfeit rFLJ and the enzyme pool that can be used to evaluate FLJ quality. Detailed molecular-level analyses allow us to decipher the relationship between metabolic pathways involved in processing active medicinal compounds and gene expressions of their processing enzymes. Our evolutionary analysis revealed specific functional divergence of orthologs and paralogs, which lead to variation in gene functions that govern the profile of active compounds.
BMC Genomics 05/2012; 13:195. · 4.07 Impact Factor
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ABSTRACT: Nano-scale TiO(2) photocatalysts co-doped by rare earth ions (La(3+), Ce(3+)) and heteropolyacids were designed and prepared by sol-gel method to probe synergistic effect on photocatalytic elimination of organic compounds, and their physicochemical properties were characterized by X-ray diffraction (XRD), specific surface area and porosity (BET and BJH), high resolution transmission electron microscopy (HRTEM), UV-vis diffuse reflectance spectroscopy (UV-vis DRS), and X-ray photoelectron spectroscopy (XPS) as well as Raman spectroscopy. The photocatalytic activity of prepared catalysts was evaluated by the degradation of methylene blue (MB) in water under UV-light irradiation. The results showed that the co-doping of the rare earth ions and heteropolyacids can significantly improve the photocatalytic activity of prepared composite photocatalysts due to the efficient inhibition of the recombination of photogenerated electron-hole pairs. The enhancement mechanism of co-doping of the rare earth ions and heteropolyacids on TiO(2) is also discussed.
Journal of Colloid and Interface Science 05/2012; 380(1):121-7. · 3.07 Impact Factor
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Zeng-ming Xue,
Wei-ju Li,
Chang-sheng Ma,
Shao-ping Nie,
Jian-zeng Dong,
Xiao-hui Liu,
Jun-ping Kang,
Qiang Lü,
Xin DU, Xiao Wang,
Fang Chen,
Yu-jie Zhou,
Shu-zheng Lü,
Fang-jiong Huang,
Cheng-xiong Gu,
Xue-si Wu
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ABSTRACT: The optimal revascularization strategy in patients with heart failure with preserved ejection fraction (HFPEF) remains unclear. The aim of the present study was to compare the effects of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with HFPEF.
From July 2003 through September 2005, a total of 920 patients with coronary artery disease (CAD) and HFPEF (ejection fraction ≥ 50%) underwent PCI (n = 350) or CABG (n = 570). We compared the groups with respect to the primary outcome of mortality, and the secondary outcomes of main adverse cardiac and cerebral vascular events (MACCE), including death, myocardial infarction, stroke and repeat revascularization, at a median follow-up of 543 days.
In-hospital mortality was significantly lower in the PCI group than in the CABG group (0.3% vs. 2.5%, adjusted P = 0.016). During follow-up, there was no significant difference in the two groups with regard to mortality rates (2.3% vs. 3.5%, adjusted P = 0.423). Patients receiving PCI had higher MACCE rates as compared with patients receiving CABG (13.4% vs. 4.0%, adjusted P < 0.001), mainly due to higher rate of repeat revascularization (adjusted P < 0.001). Independent predictors of mortality were age, New York Heart Association (NYHA) class and chronic total occlusion.
Among patients with CAD and HFPEF, PCI was shown to be as good as CABG with respect to the mortality rate, although there was a higher rate of repeat revascularization in patients undergoing PCI.
Chinese medical journal 03/2012; 125(6):1000-4. · 0.86 Impact Factor
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ABSTRACT: Er3+, montmorillonite (MMT) and H3PWl2O40 co-doped TiO2 photocatalyst (Er-H3PWl2O40-MMT/TiO2) was prepared by sol-gel method, and characterized by X-ray diffraction (XRD), specific surface area and porosity (BET and BJH), high resolution transmission electron microscopy (HRTEM) and Raman spectrum. The photocatalytic activity of the Er-H3PWl2O40-MMT/TiO2 was evaluated by the degradation of methylene blue (MB) under UV light irradiation. The experimental results of MB degradation demonstrated that the photocatalytic activity of Er-H3PWl2O40-MMT/TiO2 was significantly enhanced due to better separation of photogenerated electron-hole pairs, and its activity was absolutely higher than P-25 TiO2.
Integrated Ferroelectrics 01/2011; 127(1):141-149. · 0.30 Impact Factor
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ABSTRACT: Various approaches have been used to improve the efficacy of DNA vaccination, including the incorporation of molecular adjuvants. Because the CD40 ligand-CD40 interaction plays a major role in initiating immune responses, we sought to develop a molecular adjuvant targeting this interaction.
We immunized mice with a foot-and-mouth disease virus DNA vaccine, pcD-VP1, together with a CD40-expressing plasmid, pcD-CD40. We found that pcD-CD40 induced anti-CD40 antibodies, which temporally correlated with the augmented production of anti-VP1 antibody. pcD-CD40 similarly augmented the humoral response of another DNA vaccine that targets hepatitis B virus, and passive transfer of anti-CD40 antisera also showed a similar effect. Furthermore, the pcD-CD40-elicited anti-CD40 antibodies were able to activate the CD40 signal pathway in antigen-presenting cells in vitro, which led to the maturation of dendritic cells (DCs) and DC-mediated T cell activation. Thus, pcD-CD40 augments DNA vaccination by inducing anti-CD40 antibodies, which in turn promotes T cell activation.
This is the first reported 'proadjuvant' that augments DNA vaccination indirectly by eliciting agonistic antibodies.
The Journal of Gene Medicine 11/2009; 12(1):97-106. · 2.48 Impact Factor
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ABSTRACT: Synthetic oligodeoxynucleotides (ODNs) such as CpG can stimulate B and plasmacytoid dendritic cells in vertebrate immune systems. Several studies showed that non-CpG ODNs could also induce strong stimulation of B and T cells. PyNTTTTGT ODNs, non-CpG ODNs, can activate and cause immunoglobulin secretion by B cells and proliferation of T cells in vivo. By using PyNTTTTGT ODNs as an adjuvant for a FMDV DNA vaccine, we found that levels of antibody production, T-cell proliferation, and CTL activity were significantly increased compared with the DNA vaccine alone. Compared with the adjuvant effects of CpG ODNs on DNA vaccination, similar levels of antibody production and T-cell proliferation, and higher levels of CTL activity and IFN-gamma expression in CD8 T cells were induced by the IMT504 ODNs. On the other hand, RT-PCR results show that IMT504 ODN may activate the DNA sensor of DAI (DNA-dependent activator of IFN regulatory factors) and partially stimulate TLR9. At this point, the PyNTTTTGT prototype IMT504 ODN can reasonably be predicted to be a good adjuvant for FMDV DNA vaccine in small animals, but its efficacy in larger animals remains to be explored.
Viral immunology 05/2009; 22(2):131-8. · 1.78 Impact Factor
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ABSTRACT: To improve the immune response to HBsAg DNA vaccine and clear HBV, we investigated co-stimulatory molecule OX40L as adjuvant effect on the humoral and cellular immune responses to HBV DNA vaccine by immunizing mice with HBV DNA vaccine plus OX40L.
We immunized the C57BL/6 mice with pcDS2 alone, or with OX40L and candidate DNA vaccine against HBV (pcDS2) together by intramuscular injection. The immunization was performed on week 0, 2, 4. The concentration of the anti-HBs (IgG) and isotypes (IgG1, IgG2a), the stimulated index of T lymphocyte proliferation, and the expression of IL-4 and IFN-gamma in CD4+ T cell and IFN-gamma in CD8+ T cell, specific in vivo cytotoxic T lymphocyte (CTL) activity were detected at week 6.
The concentration of the anti-HBs IgG induced by pcDS2 plus OX40L groups was much higher than that induce by pcDS2 alone, and the levels of IgG isotype of IgG2a were generally higher than IgG1 in all groups of mice immunized with different plasmids. Compared to mice immunized with pcDS2 alone, the pcDS2 plus OX40L group increased the stimulated index (SI) of T cell proliferation and elicited a higher level of IFN-gamma and IL-4 in CD4+ T cells and a higher level of IFN-gamma in CD8+ T cells. In all groups, OX40L plus pcDS2 induced significantly robust in vivo CTL response.
The co-immunization of OX40L and HBV DNA vaccine can enhance the humoral and cellular immune responses, especially CTL activity.
ACTA MICROBIOLOGICA SINICA 04/2009; 49(3):357-62.
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Xiao Wang,
Xinyu Zhang,
Youming Kang,
Huali Jin,
Xiaogang Du,
Gan Zhao,
Yang Yu,
Jinyao Li,
Baowei Su,
Chang Huang,
Bin Wang
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ABSTRACT: Aerosol transmission of foot and mouth disease virus (FMDV) is believed to be an important route of infection. Induction of mucosal response is thought to be effective way against such infection. Various approaches have been developed including the use of molecules adjuvant and polymers delivery for the mucosal delivery of DNA vaccine. In this study, using low molecular weight chitosan as a delivery vehicle, we investigated whether co-administration intranasally of the FMDV DNA vaccine, pcD-VP1 and a construct expressing IL-15 as the molecular adjuvant can enhance mucosal and systemic immune responses in animals. Compared to the group intranasally immunized with pcD-VP1 alone, the group immunized with the molecular adjuvant not only was induced higher level of mucosal sIgA but also serum IgG. Interestingly, intranasal delivery of the IL-15 construct with pcD-VP1 significantly enhanced the cell-mediated immunity (CMI) compared to the pcD-VP1 alone, as evidenced by the higher level of antigen-specific T-cell proliferation, cytotoxic T lymphocyte (CTL) response and higher expressions of IFN-gamma in both CD4+ and CD8+ T cells inform the spleen and mucosal sites. Consistently, IL-15 as adjuvant provided higher level of FMDV neutralizing antibody against FMDV and high secretions of IgA producing cells in mucosal tissues. Taken together, the results demonstrated that intranasal delivery of IL-15 as a mucosal adjuvant can enhance the antigen-specific mucosal and systemic immune responses, which may provide a protection against the FMDV initial infection.
Vaccine 06/2008; 26(40):5135-44. · 3.77 Impact Factor
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ABSTRACT: Various approaches have been developed to improve efficacy of DNA vaccination, such as the use of plasmid expressing cytokine as a molecular adjuvant. In this study, we investigated whether co-inoculation of a construct expressing either IL-6 or TNF-alpha as the molecular adjuvant with FMDV DNA vaccine, pcD-VP1, can increase immune responses. Compared to the group immunized with pcD-VP1 alone, the co-inoculation with either molecular adjuvant induced a higher ratio of IgG2a/IgG1, higher levels of expression of IFN-gamma in CD4+ and CD8+ T cells, IL-4 in CD4+ T cells, and in vivo antigen-specific cytotoxic response. Both adjuvants induced maturation of dendritic cells, suggesting a correlation between the initiating innate response and subsequent activating adaptive immune responses. Together, the results demonstrate that IL-6 and TNF-alpha used as molecular adjuvants can enhance the antigen-specific cell-mediated responses elicited by VP1 DNA vaccine.
Vaccine 05/2008; 26(40):5111-22. · 3.77 Impact Factor
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Xiao Wang,
Huali Jin,
Xiaogang Du,
Chun Cai,
Yang Yu,
Gan Zhao,
Baowei Su,
Shan Huang,
Yanxin Hu,
Dongmei Luo,
Ruiping She,
Xinsong Luo,
Xianfang Zeng,
Xinyuan Yi,
Bin Wang
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ABSTRACT: Levamisole (LMS) as an adjuvant enhances cell-mediated immunity in DNA vaccination; we investigated the efficacy and liver immunopathology alleviation of a DNA vaccine, VR1012-SjGST-32, in a LMS formulation in the murine challenge model. Compared to controls, the VR1012-SjGST-32 plus LMS can reduce worm and egg burdens, as well as, immunopathological complications associated chronic inflammation significantly in liver, which were apparently associated with Th1-type response. Together, these results suggest that the LMS as a potential Schistosome DNA vaccine adjuvant can enhance both worm killing and disease prevention, which is possibly mediated through the induction of a strong Th1-dominant environment in immunized mice.
Vaccine 04/2008; 26(15):1832-45. · 3.77 Impact Factor
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ABSTRACT: Soil erosion is recognized as one of the major environmental problems in the Three Gorges Region (TGR). We carried out a six years’ study on the effects of different alley crops on runoff, losses of soil and nutrients, and the position related variation of soil nutrients along slope. Two experimental sites were selected with slope of 15° and 32°, respectively. Four treatments were applied at each site: Control (no alley crop); PN (Paspalum notatum as contour alley crop); HC (Hemerocallis citrina as contour alley crop); AH (Arachis hypogaea as contour alley crop). Results indicated that nutrient loss in runoff in the Control treatment was serious, especially the loss of nitrate (site A: NO3-N, 2.32 t ha−1 year−1, NH4-N, 0.79 t ha−1 year−1; site B: NO3-N, 7.41 t ha−1 year−1, NH4-N, 6.97 t ha−1 year−1) and phosphate (site A: 0.10 t ha−1 year−1; site B: 4.69 t ha−1 year−1). However, the nutrient losses by runoff in the other three treatments with alley crops showed significant reduction, especially the treatment of PN (site A: NO3-N, 0.36 t ha−1 year−1, NH4-N, 0.26 t ha−1 year−1, PO4-P, 0.026 t ha−1 year−1; site B: NO3-N, 1.29 t ha−1 year−1, NH4-N, 0.97 t ha−1 year−1, PO4-P, 0.18 t ha−1 year−1). Results of correlation and regression analysis indicated that there were significant relationships between runoff and soil loss in all treatments, which can be described by power function. Alley crop planting greatly reduced the position related variation of soil nutrient status along the slopes compared with Control treatment, especially the PN treatment.Research highlights▶ Alley crop planting can significantly reduce runoff and soil losses. ▶ Among the three alley crops, Paspalum natatum was the most effective alley crop on water and soil conservation. ▶ Runoff and soil losses were significantly correlated and the relationship between them could be described by power function. ▶ The runoff nutrient losses and nutrient concentrations of treatments with alley crops were prominently lower than those of conventional tillage method. ▶ The slope with high gradient was not suitable for farming and should be returned to forestry because of the high soil and nutrient loss. ▶ The TN and TP concentrations in runoff under conventional tillage treatment were above the critical values for eutrophication. ▶ Position related variations of soil nutrients along slope were found in all the treatments, but alley crop planting reduced the variation.
Soil and Tillage Research 110(2):243-250. · 2.42 Impact Factor
