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https://www.readbyqxmd.com/read/28110125/chemical-defined-and-albumin-free-generation-of-human-atrial-and-ventricular-myocytes-from-human-pluripotent-stem-cells
#1
Fei Pei, Junjie Jiang, Shuyun Bai, Henghua Cao, Luyang Tian, Ya Zhao, Chuanxiu Yang, Haiheng Dong, Yue Ma
Most existing culture media for cardiac differentiation of human pluripotent stem cells (hPSCs) contain significant amounts of albumin. For clinical transplantation applications of hPSC-derived cardiomyocytes (hPSC-CMs), culturing cells in an albumin containing environment raises the concern of pathogen contamination and immunogenicity to the recipient patients. In addition, batch-to-batch variation of albumin may cause the inconsistent of hPSC cardiac differentiation. Here, we demonstrated that antioxidants l-ascorbic acid, trolox, N-acetyl-l-cysteine (NAC) and sodium pyruvate could functionally substitute albumin in the culture medium, and formulated an albumin-free, chemical-defined medium (S12 medium)...
January 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28110081/isolation-and-partial-characterization-of-an-immunogenic-antigen-of-giardia-lamblia
#2
Jael Quintero, Alejandra Valdez, Brenda Samaniego, Gloria Lopez-Romero, Humberto Astiazaran-Garcia, Lucila Rascon, Linda Breci, Adriana Garibay-Escobar, Ramón Robles-Zepeda, Carlos Velazquez
Humoral and cellular immune responses play an important role during Giardia lamblia infection. Several Giardia proteins have been identified as immunogenic antigens based on their elicited humoral immune response. Poorly is known about Giardia antigens that stimulate a cellular immune response. The main purpose of this study was to isolate and partial characterize an immunogenic antigen (5G8) of G. lamblia. The 5G8 protein was isolated from G. lamblia trophozoite lysates by affinity chromatography using moAb 5G8-coupled CNBr-Sepharose...
January 18, 2017: Parasitology International
https://www.readbyqxmd.com/read/28109790/discovery-of-peptidic-mir-21-processing-inhibitor-by-mirror-image-phage-display-a-novel-method-to-generate-rna-binding-d-peptides
#3
Kotaro Sakamoto, Kentaro Otake, Tadashi Umemoto
A novel method to generate RNA binding D-peptide has been developed. To achieve the screening method, phage display was applied to "Mirrored" RNA (L-enantiomer of RNA). We have selected pre-miR21 as an initial screening target to demonstrate the method. The mirrored pre-miR-21 binding peptide sequences were successfully obtained, and were chemically synthesized using D-amino acids. D-peptide is expected to have favorable properties as a drug candidate such as protease resistance and low immunogenicity. As a result of binding evaluation of the D-peptide to pre-miR-21, the EC50 value was 440nM...
January 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28109709/the-effect-of-gamma-irradiation-conditions-on-the-immunogenicity-of-whole-inactivated-influenza-a-virus-vaccine
#4
Shannon C David, Josyane Lau, Eve V Singleton, Rachelle Babb, Justin Davies, Timothy R Hirst, Shaun R McColl, James C Paton, Mohammed Alsharifi
Gamma-irradiation, particularly an irradiation dose of 50kGy, has been utilised widely to sterilise highly pathogenic agents such as Ebola, Marburg Virus, and Avian Influenza H5N1. We have reported previously that intranasal vaccination with a gamma-irradiated Influenza A virus vaccine (γ-Flu) results in cross-protective immunity. Considering the possible inclusion of highly pathogenic Influenza strains in future clinical development of γ-Flu, an irradiation dose of 50kGy may be used to enhance vaccine safety beyond the internationally accepted Sterility Assurance Level (SAL)...
January 18, 2017: Vaccine
https://www.readbyqxmd.com/read/28109293/genetic-instability-and-increased-mutational-load-which-diagnostic-tool-best-direct-patients-with-cancer-to-immunotherapy
#5
Giuseppe Palmieri, Maria Colombino, Antonio Cossu, Antonio Marchetti, Gerardo Botti, Paolo A Ascierto
The occurrence of high rates of somatic mutations in cancer is believed to correspond to increased frequency of neo-epitope formation and tumor immunogenicity. Thus, classification of patients with cancer according to degree a somatic hyper-mutational status could be proposed as a predictive biomarker of responsiveness to immunotherapy with immune checkpoint inhibitors. Here, we discuss the suitable and reliable tests easily adoptable in clinical practice to assess somatic mutational status in patients with advanced cancer...
January 21, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28108340/rna-seq-transcriptome-analysis-of-the-olive-flounder-paralichthys-olivaceus-kidney-response-to-vaccination-with-heat-inactivated-viral-hemorrhagic-septicemia-virus
#6
Jee Youn Hwang, Mun Gyeoung Kwon, Sung-Hee Jung, Myoung Ae Park, Dong-Wook Kim, Wang Sik Cho, Jeong Woo Park, Maeng-Hyun Son
Viral hemorrhagic septicemia (VHS) is a highly contagious disease of cultured flounder caused by VHS virus (VHSV). To develop effective VHSV vaccines, it is essential to understand the molecular mechanisms underlying the host's protective response against VHSV. The purpose of this study is to clarify which genes are involved in the protective response of olive flounder after VHSV vaccination. We first injected olive flounder intraperitoneally with 10(7) TCID50 heat-inactivated VHSV vaccine and evaluated the vaccine efficacy at 20 °C...
January 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28107939/a-sensitive-chemiluminescent-immunoassay-to-detect-chromotrope-fb-chr-fb-in-foods
#7
Kun Xu, Hao Long, Rongge Xing, Yongmei Yin, Sergei A Eremin, Meng Meng, Rimo Xi
Chromotrope FB (Chr FB) is a synthetic azo dye permitted for use in foods and medicines. An acceptable daily intake (ADI) of Chr FB was 0-0.5mg/kg in China. In this study, we synthesized a Chr FB hapten with an amino group to prepare its artificial immunogen. Polyclonal antibodies obtained from New Zealand rabbits were applied to develop an indirect competitive chemiluminescent immunoassay (icCLIA) to detect Chr FB in foods. A horseradish peroxidase (HRP)-luminol-H2O2 system was used to yield CL signal with p-iodophenol as an enhancement reagent...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28106980/structural-snapshots-of-an-engineered-cystathionine-%C3%AE-lyase-reveal-the-critical-role-of-electrostatic-interactions-in-the-active-site
#8
Wupeng Yan, Everett M Stone, Yan Jessie Zhang
Enzyme therapeutics that can degrade L-methionine (L-Met) are of great interest as numerous malignancies are exquisitely sensitive to L-Met depletion. To exhaust the pool of the methionine in human serum, we previously engineered an L-Met degrading enzyme based on the human cystathionine-γ-lyase scaffold (hCGL-NLV) in order to circumvent immunogenicity and stability issues observed in the preclinical application of bacterial derived methionine-γ-lyases (MGL). To gain further insights into structure/activity relationships governing the chemistry of the hCGL-NLV lead molecule, we undertook a biophysical characterization campaign that captured crystal structures (2...
January 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28106117/norovirus-p-particle-based-active-a%C3%AE-immunotherapy-elicits-sufficient-immunogenicity-and-improves-cognitive-capacity-in-a-mouse-model-of-alzheimer-s-disease
#9
Lu Fu, Yingnan Li, Yue Hu, Yayuan Zheng, Bin Yu, Haihong Zhang, Jiaxin Wu, Hui Wu, Xianghui Yu, Wei Kong
Disease-modifying immunotherapies focusing on reducing amyloid-beta (Aβ) deposition are the main treatment for Alzheimer's disease (AD). However, none of the Aβ immunotherapies has produced clinically meaningful results to date. The main reason for this lack of efficacy is that the vaccine induces insufficiently high antibody titers, as it contains small B-cell epitope of Aβ to avoid Aβ42-specific T-cell activation. With the aim of generating a potent AD vaccine, we designed the protein PP-3copy-Aβ1-6-loop123, comprising three copies of Aβ1-6 inserted into three loops of a novel vaccine platform, the norovirus P particle, which could present Aβ at its surface and remarkably enhance the immunogenicity of the vaccine...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105653/properdin-and-factor-h-production-by-human-dendritic-cells-modulates-their-t-cell-stimulatory-capacity-and-is-regulated-by-ifn-%C3%AE
#10
Karen O Dixon, Joseph O'Flynn, Ngaisah Klar-Mohamad, Mohamed R Daha, Cees van Kooten
Dendritic cells (DCs) and complement are both key members of the innate and adaptive immune response. Recent experimental mouse models have shown that production of alternative pathway (AP) components by DCs strongly affects their ability to activate and regulate T-cell responses. In this study we investigated the production and regulation of properdin (fP) and factor H (fH) both integral regulators of the AP, by DCs and tolerogenic DCs (tolDCs). Both fP and fH were produced by DCs, with significantly higher levels of both AP components produced by tolDCs...
January 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28104165/highly-immunogenic-dqb1-mismatch-eplets-are-associated-with-development-of-chronic-active-antibody-mediated-rejection-a-first-report-from-japan
#11
D Iwami, K Hotta, H Sasaki, T Hirose, H Higuchi, Y Takada, N Shinohara
BACKGROUND: De novo donor-specific antibody (dnDSA), especially against class II HLA, correlates with chronic active antibody-mediated rejection (CAAMR), which eventually leads to graft loss. It would be helpful if we could identify the patients at high risk of dnDSA development in terms of histocompatibility. Structure-based matching strategy assessing mismatched epitopes/eplets by comparing polymorphic amino acid sequences can predict the risk of development of dnDSA and CAAMR. However, it has not been evaluated in Japanese patients whose diversity in HLA is limited...
January 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28103328/a-pre-clinical-safety-evaluation-of-sbp-hbsag-binding-protein-adjuvant-for-hepatitis-b-vaccine
#12
Jingbo Wang, Caixia Su, Rui Liu, Baoxiu Liu, Inam Ullah Khan, Jun Xie, Naishuo Zhu
Although adjuvants are a common component of many vaccines, there are few adjuvants licensed for use in humans due to concerns about their toxic effects. There is a need to develop new and safe adjuvants, because some existing vaccines have low immunogenicity among certain patient groups. In this study, SBP, a hepatitis B surface antigen binding protein that was discovered through screening a human liver cDNA expression library, was introduced into hepatitis B vaccine. A good laboratory practice, non-clinical safety evaluation was performed to identify the side effects of both SBP and SBP-adjuvanted hepatitis B vaccine...
2017: PloS One
https://www.readbyqxmd.com/read/28103319/an-hsv-2-trivalent-vaccine-is-immunogenic-in-rhesus-macaques-and-highly-efficacious-in-guinea-pigs
#13
Sita Awasthi, Lauren M Hook, Carolyn E Shaw, Bapi Pahar, Jacob A Stagray, David Liu, Ronald S Veazey, Harvey M Friedman
A genital herpes vaccine is urgently needed to prevent pain and suffering, reduce the incidence of neonatal herpes, and decrease the risk of HIV acquisition and transmission that accompanies genital infection. We evaluated a trivalent HSV-2 subunit antigen vaccine administered with CpG and alum in rhesus macaques and guinea pigs. The vaccine contains glycoproteins C, D and E (gC2, gD2, gE2) to block virus entry by gD2 and immune evasion by gC2 and gE2. In rhesus macaques, the trivalent vaccine induced plasma and mucosa neutralizing antibodies, antibodies that block gC2 and gE2 immune evasion activities, and stimulated CD4 T cell responses...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28103317/genetically-thermo-stabilised-immunogenic-poliovirus-empty-capsids-a-strategy-for-non-replicating-vaccines
#14
Helen Fox, Sarah Knowlson, Philip D Minor, Andrew J Macadam
While wild type polio has been nearly eradicated there will be a need to continue immunisation programmes for some time because of the possibility of re-emergence and the existence of long term excreters of poliovirus. All vaccines in current use depend on growth of virus and most of the non-replicating (inactivated) vaccines involve wild type viruses known to cause poliomyelitis. The attenuated vaccine strains involved in the eradication programme have been used to develop new inactivated vaccines as production is thought safer...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28102671/structural-analysis-of-glycosylated-intact-hiv-1-gp120-b12-antibody-complex-using-hydroxyl-radical-protein-footprinting
#15
Xiaoyan Li, Oliver C Grant, Keigo Ito, Aaron Wallace, Shixia Wang, Peng Zhao, Lance Wells, Shan Lu, Robert J Woods, Joshua S Sharp
Glycoprotein gp120 is a surface antigen and virulence factor of the human immunodeficiency virus-1 (HIV-1). Broadly neutralizing antibodies (bNAbs) that are reactive to gp120 from a variety of HIV isolates offer hope for the development of broadly effective immunogens for vaccination purposes, if the interactions between gp120 and bNAbs can be understood. From a structural perspective, gp120 is a particularly difficult system due to its size, the presence of multiple flexible regions, and the large amount of glycosylation, all of which are important in gp120-bNAb interactions...
January 19, 2017: Biochemistry
https://www.readbyqxmd.com/read/28102609/immunogenicity-of-hepatic-differentiated-human-umbilical-cord-mesenchymal-stem-cells-promoted-by-porcine-decellularized-liver-scaffolds
#16
Yi Li, Qiong Wu, Yujia Wang, Li Li, Fei Chen, Yujun Shi, Hong Bu, Ji Bao
Cell-based approaches, including hepatocyte transplantation and tissue-engineered livers, offer promising alternatives and are expected to help support patients with liver diseases until liver transplantation or recovery via regeneration of the damaged liver. However, the success of cell therapies remains dependent on how well the cells are accepted after transplantation and is directly related to their degree of immunogenicity. In this study, hepatic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) was induced in the traditional monolayer (2D) culture and newly established three-dimensional (3D) aggregation culture with the porcine decellularized liver scaffold (DLS) system (3D-DLS)...
January 19, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28102464/a-phase-i-and-pharmacokinetic-study-of-afilbercept-with-folfiri-comparison-of-chinese-and-caucasian-populations
#17
Jianming Xu, Yingxin Li, Xing Sun, Dongsheng Zhang, Rongrui Liu, Samira Ziti-Ljajic, Dongmei Shi, Fengying Xue, Nathalie Le Bail, Ruihua Xu
Background This study assessed the preliminary safety, pharmacokinetics (PK) and anti-tumor effects of aflibercept in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) in Chinese patients with previously-treated advanced solid malignancies. Patients and Methods This open-label single-arm Phase I study conducted at two centers in China included adult (≥18 years) patients with metastatic or unresectable solid malignancies who had received ≥1 prior treatment. Patients received aflibercept 4 mg/kg IV on Day 1 followed by FOLFIRI over Days 1 and 2 every 2 weeks, and were assessed for safety, tumor response, PK parameters and immunogenicity...
January 19, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28101965/a-multi-hit-hypothesis-of-bullous-pemphigoid-and-associated-neurological-disease-is-hla-dqb1-03-01-a-potential-link-between-immune-privileged-antigen-exposure-and-epitope-spreading
#18
REVIEW
K T Amber, J Zikry, M Hertl
Bullous pemphigoid (BP) is the most common autoimmune blistering disease and is linked to IgG recognition of 2 hemidesmosomal antigens, that is, BP230 (BP antigen 1) and BP180 (BP antigen 2, collagen XVII). The association of BP with other systemic diseases, particularly neurocognitive diseases, provides a potential clue in the underlying pathogenesis of BP. The role of HLA-DQB1*03:01 binding to the immunogenic portion of BP180 provides a potential mechanism by which exposure to neuronal collagen BP180 may lead to cutaneous disease...
January 19, 2017: HLA
https://www.readbyqxmd.com/read/28101961/antibody-formation-towards-porcine-tissue-in-patients-implanted-with-crosslinked-heart-valves-is-directed-to-antigenic-tissue-proteins-and-%C3%AE-gal-epitopes-and-is-reduced-in-healthy-vegetarian-subjects
#19
Ulrike Böer, Falk F R Buettner, Ariane Schridde, Melanie Klingenberg, Samir Sarikouch, Axel Haverich, Mathias Wilhelmi
BACKGROUND: Glutaraldehyde-fixed porcine heart valves (ga-pV) are one of the most frequently used substitutes for insufficient aortic and pulmonary heart valves which, however, degenerate after 10-15 years. Yet, xeno-immunogenicity of ga-pV in humans including identification of immunogens still needs to be investigated. We here determined the immunogenicity of ga-pV in patients with respect to antibody formation, identity of immunogens and potential options to reduce antibody levels. METHODS: Levels of tissue-specific and anti-αGal antibodies were determined retrospectively in patients who received ga-pV for 51 months (n=4), 25 months (n=6) or 5 months (n=4) and compared to age-matched untreated subjects (n=10) or younger subjects with or without vegetarian diet (n=12/15)...
January 18, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28101612/abolishment-of-n-glycan-mannosylphosphorylation-in-glyco-engineered-saccharomyces-cerevisiae-by-double-disruption-of-mnn4-and-mnn14-genes
#20
Yeong Hun Kim, Ji-Yeon Kang, Jin Young Gil, Sang-Yoon Kim, Keun Koo Shin, Hyun Ah Kang, Jeong-Yoon Kim, Ohsuk Kwon, Doo-Byoung Oh
Mannosylphosphorylated glycans are found only in fungi, including yeast, and the elimination of mannosylphosphates from glycans is a prerequisite for yeast glyco-engineering to produce human-compatible glycoproteins. In Saccharomyces cerevisiae, MNN4 and MNN6 genes are known to play roles in mannosylphosphorylation, but disruption of these genes does not completely remove the mannosylphosphates in N-glycans. This study was performed to find unknown key gene(s) involved in N-glycan mannosylphosphorylation in S...
January 18, 2017: Applied Microbiology and Biotechnology
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