Peptide-MHC Interaction: A Rational Approach to Vaccine Design

The goal of vaccination is to induce a protective immune response without inducing the disease itself or other undesirable effects. In the past this was achieved by giving inactivated or attenuated pathogens, with notable success in some cases, but problems of safety, efficacy or production in others. A currently pursued alternative is the construction of synthetic peptide vaccines that contain pathogen-derived determinants able to induce an immune response both at the B and the T cell level. Because T cells recognize peptide fragments which are derived from the processing of soluble proteins [1], the technical problems of epitope conformation can be largely avoided in the design of synthetic T cell sites. However the constraints presented by the extensive polymorphism of MHC antigens on one hand [2], and the obligate interaction between the antigenic peptide and the MHC molecule on the other [3], create a problem for the immune system. When an antigenic determinant does not interact favorably with the MHC molecules possessed by a given individual, T cell clones specific for this particular combination of determinant and MHC molecules cannot be activated and therefore not all individuals will respond to any one antigenic determinant. Thus in order to develop a synthetic peptide vaccine applicable to an entire population, individuals with each MHC haplotype would have to be studied to ascertain which peptides they predominantly recognize as T cell determinants.

In this review, through the work we have done on malaria sporozoite vaccine development, we should like to propose new strategies for identifying pathogen-derived sequences whose characteristics offer possible solutions to the problem of MHC restriction of the immune response for peptide vaccines.     

Cell-attachment activities of surface immobilized oligopeptides RGD,RGDS, RGDV,RGDT, and YIGSR toward five cell lines

Tetrapeptides, Arg-Gly-Asp-Ser (RGDS), Arg-Gly-Asp-Val (RGDV), and Arg-Gly-Asp-Thr (RGDT), respectively, appearing in the cell-attachment domains of fibronectin, vitronectin, and collagen, and pentapeptide Tyr-Ile-Gly-Ser-Arg (YIGSR) appearing in B1 chain of laminin, were synthesized by liquid-phase procedure. Bioactivities of RGD, RGDX (X=S, V and T), YIGSR, and YIGSR-NH₂ as cell recognition determinants were investigated by cell-attachment test using these oligopeptides immobilized to ethylene-acrylic acid copolymer (PEA) film. The cell lines used were A431, NRK, CHO-K1, HeLa.S3, and RLC-16 cells. It was found that the residue X in RGDX plays an important role for cell-attachment activity of RGDX, and, regarding YIGSR, introduction of NH₂ residue at the C-terminal of the pentapeptide enhances the cell-attachment activity.     

基于循环一致性生成对抗网络的盆腔伪CT生成方法

目的:基于循环一致性生成对抗网络（CycleGAN）,利用非配对患者盆腔部位数据,实现MRI和CT图像之间的相互转换,并对基于该模型生成的盆腔伪CT（sCT）进行精度和剂量性能的评估。方法:该CycleGAN网络包含两个生成器和两个判别器。先基于全卷积网络（FCNs）构建两个生成器,一个将2D盆腔MRI转换为2D盆腔sCT图像,另一个将CT图像转换为伪MRI（sMRI）图像。再基于FCNs构建两个判别器,用于对真实图像和生成的伪图像进行判别,提升生成图像的质量。为保证sCT图像与MRI图像的一致性,引入归一化互信息作为相似性约束损失项,对模型进行改进。训练集包括35例患者盆腔部位的T1-MRI图像和另外36例患者盆腔部位的CT图像,测试集包括10例盆腔部位患者的MRI和CT图像,评估方法包括sCT与CT图像的误差和放疗剂量伽马通过率。结果:对于测试集中所有病例,生成的sCT与真实CT图像之间的平均绝对误差（MAE）为35.537（±4.537） HU;基于体素的平均剂量差异最大为0.49%;以3%/3 mm、2%/2 mm和1%/1 mm为标准的平均伽马通过率分别高于99%、98%和95%。结论:使用CycleGAN网络和非配对患者训练数据可以生成准确且符合临床剂量精度要求的盆腔部位sCT图像。     

Synthetic magnetic resonance imaging for quantitative parameter evaluation of temporomandibular joint disorders

Objective:This study investigated the usefulness of quantitative parameters [longitudinal relaxation (T1), transverse relaxation (T2), and proton density (PD)] obtained with synthetic magnetic resonance imaging (MRI) in assessing the progression of temporomandibular joint (TMJ) disorders.Methods:For individual TMJ disorder diagnoses, the presence of disc displacement in MRI and the osseous change in cone-beam CT were investigated. Joints were classified into three stages: (1) silent stage, no disc displacement or osseous change; (2) incipient stage, presence of disc displacement and absence of osseous change; and (3) progressed stage, both disc displacement and osseous change. In synthetic MRI, the T1, T2, and PD values of the condyle bone marrow were measured simultaneously. The median T1, T2, and PD values were analyzed according to disc displacement, osseous changes, and joint stage.Results:Significant differences were observed in the T1 and PD values of joints with disc displacement or condylar osseous change compared to normal joints. The T1 and PD values also differed between the silent and progressed stages. The PD value differed between the silent and incipient groups, while the T2 value did not differ significantly among the three groups.Conclusion:The PD and T1 values of condylar bone marrow obtained from synthetic MRI can be used as sensitive indicators of TMJ disorder progression. The PD value of the bone marrow showed potential as a useful biomarker for recognizing the initial stages of TMJ disorders. Synthetic MRI is useful for the simultaneous acquisition of effective MRI parameters for evaluating TMJ disorders.     

2019年美国FDA批准上市的新药简介

2019年美国食品药品监督管理局(FDA)批准上市新药48个,其中化学小分子38个、生物制品10个。本文根据FDA批准的新药说明书以及相关文献和专利情况,简要介绍化学小分子药物的概况、适应证、作用机制、剂型规格、不良反应和合成路线等,以及生物制品的相关情况。     

合成生物学研究前沿的识别与趋势预测

目的：通过科学知识图谱的方法识别合成生物学研究前沿。方法应用参考文献共被引聚类、文献耦合聚类,通过VOSviewer绘制了合成生物学领域科学知识图谱,研究近两年文献对于聚类结构的改变。结果文献同被引分析生成7个聚类,文献耦合分析形成了32个聚类,近两年文献的加入改变了聚类原有的结构。结论耦合分析聚类比较适合研究前沿识别,合成生物工程、RNA表达、生物骨架、生物文库、生物组件等研究为该领域研究前沿。     

Identification and diagnostic value of a major antibody epitope on the 12 kDa antigen from Echinococcus granulosus (hydatid disease) cyst fluid

An IgG1 monoclonal antibody (MoAb), designated C9E7H8, has been produced against an epitope on the 12 kDa antigen of Echinococcus granulosus cyst fluid, believed to represent the smallest subunit of antigen B. This MoAb, raised against purified 12 kDa antigen eluted from a reducing SDS-PAGE gel, demonstrated strong binding to native sheep cyst fluid in ELISA and recognition of all three subunits of antigen B (at 12, 16, 23 kDa) by immunoblot under both reducing and non-reducing conditions. Immunoblot analysis also indicated that the complementary epitope is conserved amongst cyst fluids from different intermediate hosts of E. granulosus, including fluids from cysts of two distinct strains, and is present in cyst fluid from E. multilocularis. The monoclonal displays binding to a cDNA clone, EgPS-3, which we have previously shown expresses part of the 12 kDa molecule. EgPS-3, expressed as a glutathione-S-transferase fusion protein, was successful in positive detection of 74% of cystic hydatid patients, although cross-reactions were observed with 25% of sera from alveolar hydatid and 22% of sera from schistosomiasis japonica patients. Three peptides, based on the predicted amino acid sequence of EgPS-3. showed increased specificity but slightly reduced sensitivity in the detection of antibody from E. granulosus patients. The predominant epitope recognized by human antibody occurs in the Nterminal 27 amino acids (peptide 65) of EgPS-3 which also correlates with the location of the monoclonal antibody epitope.     

The application of POSS nanostructures in cartilage tissue engineering: the chondrocyte response to nanoscale geometry

Despite extensive research into cartilage tissue engineering (CTE), there is still no scaffold ideal for clinical applications. Various synthetic and natural polymers have been investigated in vitro and in vivo, but none have reached widespread clinical use. The authors investigate the potential of POSS–PCU, a synthetic nanocomposite polymer, for use in CTE. POSS–PCU is modified with silsesquioxane nanostructures that improve its biological and physical properties. The ability of POSS–PCU to support the growth of ovine nasoseptal chondrocytes was evaluated against a polymer widely used in CTE, polycaprolactone (PCL). Scaffolds with varied concentrations of the POSS molecule were also synthesized to investigate their effect on chondrocyte growth. Chondrocytes were seeded onto scaffold disks (PCU negative control; POSS–PCU 2%, 4%, 6%, 8%; PCL). Cytocompatibilty was evaluated using cell viability, total DNA, collagen and GAG assays. Chondrocytes cultured on POSS–PCU (2% POSS) scaffolds had significantly higher viability than PCL scaffolds (p < 0.001). Total DNA, collagen and sGAG protein were also greater on POSS–PCU scaffolds compared with PCL (p > 0.05). POSS–PCU (6% and 8% POSS) had improved viability and proliferation over an 18 day culture period compared with 2% and 4% POSS–PCU (p < 0.0001). Increasing the percentage of POSS in the scaffolds increased the size of the pores found in the scaffolds (p < 0.05). POSS–PCU has excellent potential for use in CTE. It supports the growth of chondrocytes in vitro and the POSS modification significantly enhances the growth and proliferation of nasoseptal chondrocytes compared with traditional scaffolds such as PCL. Copyright © 2013 John Wiley & Sons, Ltd.