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1.
《Vaccine》2016,34(20):2334-2341
Glycoconjugate vaccines are composed of capsular polysaccharides (CPSs) of a pathogenic bacteria covalently linked to carrier proteins. Pre-exposure to the carrier is known to influence the efficacy of the glycoconjugate, by inducing enhanced or suppressed anti-CPS response. Following our previous work on the immunogenicity of diphtheria toxin mutant CRM197 and formaldehyde-treated diphtheria toxoid (DT) as carriers for meningococcal A (MenA) conjugates in mouse model, we further investigated the role of the carrier on the immunological response to glycoconjugate vaccines. We previously showed that high dosage DT priming could result in carrier-induced epitopic suppression (CIES), an event that did not occur for CRM197 priming, and we observed that anti-DT IgGs could cross-react with DT based conjugates in vitro. Here, we confirmed the cross-reactivity of anti-carrier IgGs with DT conjugates in vivo. Furthermore, we analyzed the splenocytes of animals primed with the carrier and subsequently immunized with the MenA conjugate. Pre-exposure to the carrier protein, both CRM197 and DT, resulted in increased carrier-specific plasma and memory B cell response. However, only for CRM197 priming an enhanced carbohydrate-specific plasma cell response was observed. Analysis of circulating IgGs confirmed these observations. Memory to the CPS resulted to be non-influenced by carrier priming. Analysis of T helper response showed an enhancement effect for CRM197 priming, while DT priming resulted in constrained T cell activation. Stimulation with CRM197, which does not require formaldehyde detoxification, of splenocytes from animal immunized with DT suggested that the formaldehyde treatment used to produce DT might be the cause of limited presentation of the antigen to the T cells. We concluded that the dominant carrier-specific B cell response in case of limited T cell recruitment might explain the previously observed CIES phenomenon in case of DT priming. 相似文献
2.
《Vaccine》2020,38(10):2315-2325
In the preparation of glycoconjugate vaccines in clinical practice, two highly immunogenic carrier proteins, CRM197 and tetanus toxoid (TT), are predominantly conjugated with the capsular polysaccharides (CPSs) of bacterial pathogens. In addition, TT has long been used as an effective vaccine to prevent tetanus. While these carrier proteins play an important role in immunogenicity and vaccine design alike, their defined human major histocompatibility complex class II (MHCII) T cell epitopes are inadequately characterized. In this current work, we use mass spectrometry to identify the peptides from these carrier proteins that are naturally processed and presented by human B cells via MHCII pathway. The MHCII-presented peptides are screened for their T cell stimulation using primary CD4+ T cells from four healthy adult donors. These combined methods reveal a subset of eleven CD4+ T cell epitopes that proliferate and stimulate human T cells with diverse MHCII allelic repertoire. Six of these peptides stand out as potential immunodominant epitopes by responding in three or more donors. Additionally, we provide evidence of these natural epitopes eliciting more significant T cell responses in donors than previously published TT peptides selected from T cell epitope screening. This study serves toward understanding carrier protein immune responses and thus enables the use of these peptides in developing novel knowledge-based vaccines to combat persisting problems in glycoconjugate vaccine design. 相似文献
3.
人钠/二羧酸协同转运蛋白3基因调控肾小管上皮细胞线粒体膜电位的研究 总被引:1,自引:0,他引:1
目的 观察人钠/二羧酸协同转运蛋白3(hNaDC3,)对人肾脏近曲小管上皮细胞(HKC)线粒体膜电位的变化及其对细胞能量代谢的影响。方法 应用亚克隆技术构建正义pcDNA3-hNaDC3和反义pcDNA3-AhNaDC3两个真核表达载体,通过脂质体LipofectAMINE将pcDNA3-hNaDC3及pcDNA3-AhNaDC3转染至HKC细胞。克隆筛选后,用RT—PCR、Northern印迹及Western印迹鉴定外源基因的整合和表达。荧光探针JC-1观察各细胞系线粒体膜电位的变化。结果 外源hNaDC3基因稳定整合到HKC细胞基因组中,并获得高、低表达。转染正义hNaDC3cDNA的HKC细胞线粒体膜电位降低,JC-1在线粒体内形成单体,发出绿色荧光;而转染反义hNaDC3cDNA的HKC细胞线粒体膜电位略微升高,JC-1形成聚合体,发出红色荧光。结论 hNaDC3过表达引起线粒体膜电位降低,反义hNaDC3则使线粒体膜电位略微升高。提示NaDC3可能通过使线粒体膜电位下降,参与了细胞能量代谢。 相似文献
4.
A群脑膜炎多糖菌苗接种前后流脑流行规律的改变及今后预防对策 总被引:1,自引:0,他引:1
Wu Gueikuens et al. Collaboration of Provincial Sanitary Anti-epidemic Station Institute of Epidemiology Microbiology 《中国公共卫生学报》1994,13(5):263-264
本文研究了在使用菌苗预防前后的流行性脑脊髓膜炎流行强度的变迁,年龄、地区及季节分布特点,人群的易感性及带菌率之间的关系,并讨论了今后的预防措施。 相似文献
5.
四种可溶性载体对骨形态发生蛋白在小鼠体内诱导成骨活性的影响 总被引:28,自引:0,他引:28
以四种可溶性物质作为牛骨形态发生蛋白(bBMP)的载体,通过实验观察哪种物质是bBMP的有效缓释载体。将聚乙烯吡咯烷酮(PVP)、葡聚糖、羟乙基淀粉(HES)、甘露醇分别与等量bBMP复合后,注射入小鼠股部肌肉,观察组织学成骨及测定标本内钙含量。结果,bBMP/PVP有良好成骨,吸收较快,未见炎症及排斥反应,其混悬液较稳定,具有良好的适针性及可注射性,bBMP/甘露醇只有很低成骨率。其余各组未见成骨。PVP对bBMP具有满意助溶、助悬及缓释载体作用,对bBMP活性无损害,生物相容性好。 相似文献
6.
对一个脆性X染色体阳性家系进行了调查,用缺叶酸培养基(TC199)检查2名患者,脆性X检出率分别为13%,19%,本家系内尚有1名男性携带者,提示该家系脆性X染色体综合征不属于典型的X连锁隐性遗传。 相似文献
7.
8.
探讨以纤维蛋白胶(fibrin sealant,FS)为载体,复合rhBMP-2\bFGF的注射型骨修复材料,修复犬桡骨节段性缺损的作用,为其临床应用提供实验依据.实验分为:实验组(FS bFGF rhBMP-2)、对照组(FS).于12只成年健康家犬右侧桡骨中上段造成2cm缺损,制成犬桡骨2cm骨缺损实验模型,然后严密缝合皮下组织及皮肤,将实验材料经伤口周围正常皮肤注射到骨缺损处,术后4、8、16、24w进行放射学检查,术后24w,标本进行组织学和骨密度检查,研究其成骨效应.结果表明:实验组骨缺损区在成骨活跃程度、骨密度和再生髓腔结构等方面均显著优于对照组,使骨缺损得到了成功的修复(P<0.01).以纤维蛋白胶为载体复合rhBMP-2和bFGF的注射型骨修复材料,具有高效的骨修复能力,对犬的骨缺损有很好的修复效果. 相似文献
9.
磁性阿霉素白蛋白纳米粒的研制 总被引:47,自引:8,他引:39
目的:制作具有稳定磁性、能够携带化疗药物的白蛋白纳米粒,并对白蛋白纳米粒的磁性,药物含量进行检测。方法:将市售用Fe3O4粉末,经化学方法处理,制成纳米大小的Fe3O4泥糊,将Fe3O4泥糊、纯盐酸阿霉素、人体血清白蛋白按一定比例混合,通过在棉仔油中超声乳化,加热变性、乙醚洗涤等工艺制作出磁性阿霉素白蛋白纳米粒,用乙醇提取法提取磁性纳米粒中的阿霉素,并用荧光光度计测定含量。将纳米粒溶于生理盐水中,在光学显微镜下观察在磁场作用下磁性纳米粒的运动情况,通过检测溶液中的游离药物,观察在不同的加热温度下,磁性纳米粒的稳定性,并用电子显微镜观察纳米粒的内部结构。结果:磁性白蛋白纳米粒阿霉素含量为57.5μg/g,阿霉素包含率为98.3%,磁性白蛋白纳米溶液在光学显微镜下观察,在磁场的作用下,纳米粒迅速向磁铁的方向移动并发生聚集,当磁铁与纳米粒的距离加大时,纳米粒运动速度减慢,并沿磁力线的方向形成串珠状聚集。电子显微镜下观察,Fe3O4颗粒均匀分布在白蛋白纳米粒中,结论:磁性白蛋白纳米粒具有磁性稳定、靶向性强、药物包含率高、释药速率可控制的特点,为靶向药物治疗提供了可靠的载药工具。 相似文献
10.
E. Petzinger 《Naunyn-Schmiedeberg's archives of pharmacology》1981,316(4):345-349
Summary Cholic acid inhibits the uptake of demethylphalloin (DMP), in a competitive manner. The bile acid increases the Michaelis constant but not V
max of the inward transport. The inhibition constant K
i for cholate was found to be 8 M. Cholate competes for the transport system but not for intracellular binding of phallotoxins. Various experimental data presented in this paper exclude an accumulation of phallotoxins in hepatocytes by intracellular binding only.Preincubation of hepatocytes with small concentrations of either (3H)-demethylphalloin or (14C)-cholate and subsequent treatment with high concentrations of the nonlabelled compounds reduces the intracellular concentration of both radioactive substrates. In accordance with earlier findings the above results suggest a common component needed for the transport of both phallotoxins and cholic acid.This work was supported by the Deutsche Forschungsgemeinschaft 相似文献