Synthesis,Characterization and Immunological Evaluation of Self‐Adjuvanting Group A Streptococcal Vaccine Candidates Bearing Various Lipidic Adjuvanting Moieties

Four group A streptococcal glycolipopeptide vaccine candidates with different lipidic adjuvanting moieties were prepared and characterized. The immunogenicity of the compounds was evaluated by macrophage and dendritic cell uptake studies and by in vivo quantification of systemic IgG antibody by ELISA. Three of the candidates showed significant induction of the IgG response.     

Novel Simple Conjugation Chemistries for Decoration of GMMA with Heterologous Antigens

Outer Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV. Here we develop two simple and widely applicable conjugation chemistries targeting proteins or lipopolysaccharides on the surface of Generalized Modules for Membrane Antigens (GMMA), OMV spontaneously released from Gram-negative bacteria mutated to increase vesicle yield and reduce potential reactogenicity. A Design of Experiment approach was used to identify optimal conditions for GMMA activation before conjugation, resulting in consistent processes and ensuring conjugation efficiency. Conjugates produced by both chemistries induced strong humoral response against the heterologous antigen and GMMA. Additionally, the use of the two orthogonal chemistries allowed to control the linkage of two different antigens on the same GMMA particle. This work supports the further advancement of this novel platform with great potential for the design of effective vaccines.     

一种新的免疫遗传算法及其应用

为了克服基本遗传算法存在的缺点和不足,将免疫系统中抗体多样性的维持机制引入遗传算法,同时兼顾个体多样性和提高种群中个体适应度的水平,提出了基于相似性矢量距为选择概率的免疫遗传算法,并给出了此类概率选择的一般表示形式.为了防止基于相似性矢量距为选择概率的免疫遗传算法在优化过程中出现退化现象,通过在算法中引入免疫疫苗的方式,对该算法进一步加以改进.从每一代保优抗体中提取有效信息,进而得到一种新的疫苗提取方法.基于所提出的改进免疫遗传算法,提出了改进的编码方案.对20个城市的TSP问题进行研究,通过不同参数的比较,得出了算法中相关参数的取值范围.比较了6种算法的收敛速度,进一步证实了所提出算法具有良好的收敛性.     

现实场景中非接触式心率检测方法研究

现有的非接触式心冲击描记术(ballistocardiography,BCG)利用运动追踪捕捉头部微弱运动,存在着光照干扰、运动干扰等问题.针对该问题,提出了一种基于方向可调滤波器的头部微小振动检测方法(steerable filters schematic detection BCG,SD-BCG),以实现非接触式心...     

Proteome Based Approach Defines Candidates for Designing a Multitope Vaccine against the Nipah Virus

Nipah virus is one of the most harmful emerging viruses with deadly effects on both humans and animals. Because of the severe outbreaks, in 2018, the World Health Organization focused on the urgent need for the development of effective solutions against the virus. However, up to date, there is no effective vaccine against the Nipah virus in the market. In the current study, the complete proteome of the Nipah virus (nine proteins) was analyzed for the antigenicity score and the virulence role of each protein, where we came up with fusion glycoprotein (F), glycoprotein (G), protein (V), and protein (W) as the candidates for epitope prediction. Following that, the multitope vaccine was designed based on top-ranking CTL, HTL, and BCL epitopes from the selected proteins. We used suitable linkers, adjuvant, and PADRE peptides to finalize the constructed vaccine, which was analyzed for its physicochemical features, antigenicity, toxicity, allergenicity, and solubility. The designed vaccine passed these assessments through computational analysis and, as a final step, we ran a docking analysis between the designed vaccine and TLR-³ and validated the docked complex through molecular dynamics simulation, which estimated a strong binding and supported the nomination of the designed vaccine as a putative solution for Nipah virus. Here, we describe the computational approach for design and analysis of this vaccine.     

基于模拟疫苗的人工免疫系统在氯乙烯聚合间歇过程故障诊断中的应用

根据聚氯乙烯工业生产过程的工艺信息、操作规程和历史数据,利用Aspen软件建立了氯乙烯悬浮聚合间歇过程的动态仿真模型,由模拟得到的多个状态的样本数据生成正常模拟疫苗和故障模拟疫苗,结合工业数据建立正常抗体库和故障抗体库,解决了氯乙烯聚合过程故障诊断中故障样本数据缺乏的问题。利用动态时间弯曲算法和人工免疫系统对该聚合反应间歇过程进行故障诊断,具有较好的诊断效果。     

Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin

Immunotherapy of bladder cancer is known to have favorable effects, although it is difficult to determine which patients will show a good response because of the different tumor microenvironments (TME). Here, we developed a bladder cancer-on-a-chip (BCOC) to mimic the TME using three-dimensional (3D) bioprinting and microfluidic technology. We fabricated a T24 and a 5637-cell line-based BCOC that also incorporated MRC-5, HUVEC, and THP-1 cells. We evaluated the effects of TME and assessed the immunologic reactions in response to different concentrations of Bacillus Calmette–Guérin (BCG) via live/dead assay and THP-1 monocytic migration, and concentrations of growth factors and cytokines. The results show that cell viability was maintained at 15% filling density in circle-shaped cell constructs at 20 μL/min microfluidic flow rate. A 3D co-culture increased the proliferation of BCOCs. We found that the appropriate time to evaluate the viability of BCOC, concentration of cytokines, and migration of monocytes was 6 h, 24 h, and three days after BGC treatment. Lastly, the immunotherapeutic effects of BCOC increased according to BCG dosage. To predict effects of immunotherapeutic agent in bladder cancer, we constructed a 3D bioprinted BCOC model. The BCOC was validated with BCG, which has been proven to be effective in the immunotherapy of bladder cancer.     

免疫粒子群算法的改进及应用

在现有的免疫粒子群算法基础上,增加了交叉和高频变异操作,以保证种群进化的多样性,克服粒子群算法的早熟现象。本算法通过柯西变异提高算法的全局搜索能力;通过高斯变异提高算法的局部搜索能力。此外,为解决随机的、没有指导的交叉变异操作可能引起的退化现象,引入了疫苗提取和疫苗接种策略。仿真结果表明算法的收敛速度和精度都有明显提高。     

应用免疫原理的无线传感器网络入侵检测系统

为了提高无线传感器网络的安全性,将生物免疫原理应用到无线传感器网络安全问题中,设计了一个基于生物免疫原理的轻量级入侵检测系统。该系统主要完成检测器的生成和抗原检测,在检测器的生成过程中,通过离散r-连续位匹配算法简化否定选择算法;通过提取记忆免疫细胞疫苗对抗体进行接种,加快免疫算法的收敛性;通过聚类算法对记忆免疫细胞集合进行分类优化,提高了抗体的多样性。仿真实验表明,系统具有较好的检测率和较低的能耗。