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https://www.readbyqxmd.com/read/27933315/immunogenicity-of-self-tumor-associated-proteins-is-enhanced-through-protein-truncation
#1
Tim Kottke, Kevin G Shim, Vanesa Alonso-Camino, Shane Zaidi, Rosa Maria Diaz, Jose Pulido, Jill Thompson, Karishma R Rajani, Laura Evgin, Elizabeth Ilett, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher, Richard Vile
We showed previously that therapy with Vesicular Stomatitis Virus (VSV) expressing tumor-associated proteins eradicates established tumors. We show here that when cellular cDNA were cloned into VSV which retained their own poly-A signal, viral species emerged in culture which had deleted the cellular poly-A signal and also contained a truncated form of the protein coding sequence. Typically, the truncation occurred such that a Tyrosine-encoding codon was converted into a STOP codon. We believe that the truncation of tumor-associated proteins expressed from VSV in this way occurred to preserve the ability of the virus to replicate efficiently...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27933274/screening-and-identification-of-an-h-2k-b-restricted-ctl-epitope-within-the-glycoprotein-of-hantaan-virus
#2
Rui-Xue Ma, Lin-Feng Cheng, Qi-Kang Ying, Rong-Rong Liu, Tie-Jun Ma, Xiao-Xiao Zhang, Zi-Yu Liu, Liang Zhang, Wei Ye, Fang-Lin Zhang, Zhi-Kai Xu, Fang Wang, Xing-An Wu
The cytotoxic T lymphocyte (CTL) response plays a key role in controlling viral infection, but only a few epitopes within the HTNV glycoprotein (GP) that are recognized by CTLs have been reported. In this study, we identified one murine HTNV GP-derived H2-K(b)-restricted CTL epitope in C57BL/6 mice, which could be used to design preclinical studies of vaccines for HTNV infection. First, 15 8-mer peptides were selected from the HTNV GP amino acid sequence based on a percentile rank of <=1% by IEDB which is the most comprehensive collection of epitope prediction and analysis tool...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27932477/moss-produced-glycosylation-optimized-human-factor-h-for-therapeutic-application-in-complement-disorders
#3
Stefan Michelfelder, Juliana Parsons, Lennard L Bohlender, Sebastian N W Hoernstein, Holger Niederkrüger, Andreas Busch, Nicola Krieghoff, Jonas Koch, Benjamin Fode, Andreas Schaaf, Thomas Frischmuth, Martin Pohl, Peter F Zipfel, Ralf Reski, Eva L Decker, Karsten Häffner
Genetic defects in complement regulatory proteins can lead to severe renal diseases, including atypical hemolytic uremic syndrome and C3 glomerulopathies, and age-related macular degeneration. The majority of the mutations found in patients with these diseases affect the glycoprotein complement factor H, the main regulator of the alternative pathway of complement activation. Therapeutic options are limited, and novel treatments, specifically those targeting alternative pathway activation, are highly desirable...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27932443/pd-l1-blockade-enhances-response-of-pancreatic-ductal-adenocarcinoma-to-radiotherapy
#4
Abul Azad, Su Yin Lim, Zenobia D'Costa, Keaton Jones, Angela Diana, Owen J Sansom, Philipp Kruger, Stanley Liu, W Gillies McKenna, Omer Dushek, Ruth J Muschel, Emmanouil Fokas
Pancreatic ductal adenocarcinoma (PDAC) is considered a non-immunogenic tumor, and immune checkpoint inhibitor monotherapy lacks efficacy in this disease. Radiotherapy (RT) can stimulate the immune system. Here, we show that treatment of KPC and Pan02 murine PDAC cells with RT and gemcitabine upregulated PD-L1 expression in a JAK/Stat1-dependent manner. In vitro, PD-L1 inhibition did not alter radio- and chemosensitivity. In vivo, addition of anti-PD-L1 to high (12, 5 × 3, 20 Gy) but not low (6, 5 × 2 Gy) RT doses significantly improved tumor response in KPC and Pan02 allografts...
December 8, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27932417/molecular-pathways-the-necrosome-a-target-for-cancer-therapy
#5
Lena Seifert, George Miller
Necroptosis is a caspase 8-independent cell death that requires co-activation of receptor-interacting protein (RIP) 1 and RIP 3 kinases. The necrosome is a complex consisting of RIP1, RIP3 and Fas-associated protein with death domain (FADD) leading to activation of the pseudokinase mixed lineage kinase like (MLKL) followed by a rapid plasma membrane rupture and inflammatory response through the release of damage-associated molecular patterns (DAMPs) and cytokines. The necrosome has been shown to be relevant in multiple tumor types, including pancreatic adenocarcinoma, melanoma and several hematological malignancies...
December 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27932206/detailed-analysis-of-balb-c-mice-challenged-with-wild-type-rotavirus-edim-provide-an-alternative-for-infection-model-of-rotavirus
#6
Jialiang Du, Zhiling Lan, Yueyue Liu, Yan Liu, Yanchao Li, Xiangming Li, Tai Guo
Mouse is one of the infection animal models for rotavirus. Since the optimal age of mouse sensitive to rotavirus infection thus far has not been unified, we elucidated clinical symptoms, immune responses and pathological changes of mice in different ages after challenged by murine rotavirus wild strain EDIM (Epidemic Diarrhea of Infant Mice) to provide data for the estimation. One-week-old, two-week-old, and three-week-old BALB/c mice were inoculated with EDIM in the challenge dose of 235 ID50, 470 ID50 and 705 ID50 respectively and were compared to mock-infected controls...
December 5, 2016: Virus Research
https://www.readbyqxmd.com/read/27932151/kidney-transplantation-with-ultralong-term-42-years-survival-of-a-100-year-old-graft
#7
E Nascimento, F M Lucas-Junior, R A Fabreti-Oliveira, B Vilela, E R F Tavora, J P L Silva, A Salomão-Filho
BACKGROUND: In kidney transplantation, long-term graft survival has improved over the last few decades. Study to understand ultralong-term graft survival with graft functioning is rare, but a few researchers have tried to explain the factors involved in long-term graft survival. In this report, we explore the predictive factors that can be involved in ultralong-term graft survival. MATERIAL AND METHODS: Immunologic evaluations of the patients were performed using crossmatch (XM), serological, and high-resolution HLA typing for 8 loci...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931513/immunogenicity-of-anti-hla-antibodies-in-pancreas-and-islet-transplantation
#8
Benjamin Chaigne, Kirsten Geneugelijk, Benot Bdat, Mohamed Alibashe Ahmed, Gideon Hnger, Sophie de Seigneux, Sandrine Demuylder-Mischler, Thierry Berney, Eric Spierings, Sylvie Ferrari-Lacraz, Jean Villard
The aim of the current study was to characterize the anti-HLA antibodies before and after pancreatic islet or pancreas transplantation. We assessed the risk of anti-donor-specific antibody (DSA) sensitization in a single-center, retrospective clinical study at Geneva University Hospital. Data regarding clinical characteristics, graft outcome, HLA mismatch, donor HLA immunogenicity, and anti-HLA antibody characteristics were collected. Between January 2008 and July 2014, 18 patients received islet transplants, and 26 patients received a pancreas transplant...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27930979/hp91-immunoadjuvant-an-hmgb1-derived-peptide-for-development-of-therapeutic-hpv-vaccines
#9
Somayeh Talebi, Azam Bolhassani, Seyed Mehdi Sadat, Rouhollah Vahabpour, Elnaz Agi, Sepideh Shahbazi
BACKGROUND: High percentage of human cervical malignancy is related to human papillomavirus (HPV) infections. Thus, it is important to find novel non-invasive treatment strategies among various therapeutic HPV vaccines. In current study, we investigated the protective and therapeutic effects of DNA- and protein-based vaccines using HPV16 E7 as a model antigen in tumor mice model. In this line, the full length of high-mobility group box 1 (HMGB1) protein as well as an HMGB1-derived short peptide (Hp91) was used as an adjuvant for stimulating adaptive immunity and developing the potency of these vaccines...
December 5, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27930728/profiling-and-identification-of-novel-immunogenic-proteins-of-staphylococcus-hyicus-zc-4-by-immunoproteomic-assay
#10
Lei Wang, Zhi-Wei Wu, Yan Li, Jian-Guo Dong, Le-Yi Zhang, Peng-Shuai Liang, Yan-Ling Liu, Ya-Hua Zhao, Chang-Xu Song
Staphylococcus hyicus has caused great losses in the swine industry by inducing piglet exudative epidermitis (EE), sow mastitis, metritis, and other diseases and is a threat to human health. The pathogenesis of EE, sow mastitis, and metritis involves the interaction between the host and virulent protein factors of S. hyicus, however, the proteins that interact with the host, especially the host immune system, are unclear. In the present study, immunoproteomics was used to screen the immunogenic proteins of S...
2016: PloS One
https://www.readbyqxmd.com/read/27930644/immunotherapy-for-the-treatment-of-breast-cancer-checkpoint-blockade-cancer-vaccines-and-future-directions-in-combination-immunotherapy
#11
Heather L McArthur, David B Page
Immunotherapy encompasses both vaccines that direct immune responses to tumor-associated antigens, and checkpoint blocking antibodies that inhibit immune system suppression by targeting key pathways mediated by cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 (PD-1), and programmed death ligand 1 (PD-L1). Both of these approaches currently are being explored as potential strategies for the treatment of breast cancer. Recent studies suggest that immunotherapy is poised to change the therapeutic landscape for some breast cancers...
November 2016: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/27930268/recombinant-bacillus-subtilis-spores-expressing-cholera-toxin-b-subunit-and-helicobacter-pylori-urease-b-confers-protection-against-h-pylori-in-mice
#12
Zhenwen Zhou, Hui Dong, Shuwen Yao, Yanmei Huang, Bingshao Liang, Yongqiang Xie, Yan Long, Jialiang Mai, Sitang Gong
Helicobacter pylori infection is associated with chronic gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. The limitations of current therapies for Helicobacter pylori infection include poor compliance and antibiotic resistance. Therefore, an effective anti-H. pylori vaccine would be an alternative or complement to antibiotic treatment. Urease B (UreB) is considered an ideal vaccine antigen against H. pylori infection. In this study, cholera toxin B subunit (CTB), a mucosal adjuvant, was used to enhance the immunogenicity of novel Bacillus subtilis spores vaccine that express CTB-UreB along with the B...
December 8, 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27929750/purification-and-immunogenicity-of-hemagglutinin-from-highly-pathogenic-avian-influenza-virus-h5n1-expressed-in-nicotiana-benthamiana
#13
Teen-Lee Pua, Xiao Ying Chan, Hwei-San Loh, Abdul Rahman Omar, Vidadi Yusibov, Konstantin Musiychuk, Alexandra C Hall, Megan V Coffin, Yoko Shoji, Jessica A Chichester, Hong Bi, Stephen J Streatfield
Highly pathogenic avian influenza (HPAI) H5N1 is an ongoing global health concern due to its severe sporadic outbreaks in Asia, Africa and Europe, which poses a potential pandemic threat. The development of safe and cost-effective vaccine candidates for HPAI is considered the best strategy for managing the disease and addressing the pandemic preparedness. The most potential vaccine candidate is the antigenic determinant of influenza A virus, hemagglutinin (HA). The present research was aimed at developing optimized expression in Nicotiana benthamiana and protein purification process for HA from the Malaysian isolate of H5N1 as a vaccine antigen for HPAI H5N1...
December 8, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27929748/evaluation-of-inflammatory-and-immune-responses-in-long-term-cultured-human-precision-cut-lung-slices
#14
Angela Temann, Tatiana Golovina, Vanessa Neuhaus, Carolann Thompson, Jessica A Chichester, Armin Braun, Vidadi Yusibov
The development of systems that are more accurate and time-efficient in predicting safety and efficacy of target products in humans are critically important in reducing the cost and duration of pharmaceutical development. To circumvent some of the limitations imposed by the use of animal models, ex vivo systems, such as precision-cut lung slices (PCLS), have been proposed as an alternative for evaluating safety, immunogenicity and efficacy of vaccines and pharmaceuticals. In this study, we have established a human PCLS system and methodology for PCLS cultivation that can provide long-term viability and functionality in culture...
December 8, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27929422/co-administration-of-lipid-nanoparticles-and-sub-unit-vaccine-antigens-is-required-for-increase-in-antigen-specific-immune-responses-in-mice
#15
Elizabeth A Thoryk, Gokul Swaminathan, Steven Meschino, Kara S Cox, Marian Gindy, Danilo R Casimiro, Andrew J Bett
A vast body of evidence suggests that nanoparticles function as potent immune-modulatory agents. We have previously shown that Merck proprietary Lipid NanoParticles (LNPs) markedly boost B-cell and T-cell responses to sub-unit vaccine antigens in mice. To further evaluate the specifics of vaccine delivery and dosing regimens in vivo, we performed immunogenicity studies in BALB/c and C57BL/6 mice using two model antigens, Hepatitis B Surface Antigen (HBsAg) and Ovalbumin (OVA), respectively. To assess the requirement for co-administration of antigen and LNP for the elicitation of immune responses, we evaluated immune responses after administering antigen and LNP to separate limbs, or administering antigen and LNP to the same limb but separated by 24 h...
December 6, 2016: Vaccines
https://www.readbyqxmd.com/read/27928714/phase-i-study-of-nivolumab-an-anti-pd-1-antibody-in-patients-with-malignant-solid-tumors
#16
Noboru Yamamoto, Hiroshi Nokihara, Yasuhide Yamada, Takashi Shibata, Yosuke Tamura, Yoshitaka Seki, Kazunori Honda, Yuko Tanabe, Hiroshi Wakui, Tomohide Tamura
Background This study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of single and multiple doses of nivolumab in Japanese patients with malignant solid tumors. Subjects and Methods This was an open-label, dose-escalation study in 17 patients with advanced solid tumors with a life expectancy of ≥3 months. Patients were observed for 3 weeks after a single dose of nivolumab at 1, 3, 10 or 20 mg/kg, then received the same dose of nivolumab every 2 weeks until unacceptable toxicity or disease progression occurred...
December 8, 2016: Investigational New Drugs
https://www.readbyqxmd.com/read/27928487/immunoreactivity-evaluation-of-a-new-recombinant-chimeric-protein-against-brucella-in-the-murine-model
#17
Abbas Abdollahi, Shahla Mansouri, Jafar Amani, Mahdi Fasihi-Ramandi, Mohammad Moradi
BACKGROUND AND OBJECTIVES: Brucellosis is an important health problem in developing countries and no vaccine is available for the prevention of infection in humans. Because of clinically infectious diseases and their economic consequences in human and animals, designing a proper vaccine against Brucella is desirable. In this study, we evaluated the immune responses induced by a designed recombinant chimera protein in murine model. MATERIALS AND METHODS: Three immunodominant antigens of Brucella have been characterized as potential immunogenic and protective antigens including: trigger factor (TF), Omp31 and Bp26 were fused together by EAAAK linkers to produce a chimera (structure were designed in silico), which was synthesized, cloned, and expressed in E...
June 2016: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/27928017/a-temperature-sensitive-live-attenuated-canine-influenza-virus-h3n8-vaccine
#18
Aitor Nogales, Laura Rodriguez, Caroline Chauché, Kai Huang, Emma C Reilly, David J Topham, Pablo R Murcia, Colin R Parrish, Luis Martínez-Sobrido
: Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27928002/adjuvanting-an-siv-vaccine-with-tlr-ligands-encapsulated-in-nanoparticles-induces-persistent-antibody-responses-and-enhanced-protection-in-trim5%C3%AE-restrictive-macaques
#19
Sudhir Pai Kasturi, Pamela A Kozlowski, Helder I Nakaya, Matheus C Burger, Pedro Russo, Mathew Pham, Yevgeniy Kovalenkov, Eduardo L V Silveira, Colin Havenar-Daughton, Samantha L Burton, Katie M Kilgore, Mathew J Johnson, Rafiq Nabi, Traci Legere, Zarpheen Jinnah Sher, Xuemin Chen, Rama R Amara, Eric Hunter, Steven E Bosinger, Paul Spearman, Shane Crotty, Francois Villinger, Cynthia A Derdeyn, Jens Wrammert, Bali Pulendran
: Our previous work has shown that antigens adjuvanted with specific ligands for toll-like receptor 4 (TLR4) and TLR7/8 encapsulated in poly (lactic-co-glycolic acid) (PLGA) based nanoparticles (NP), induced robust and durable immune responses in mice and macaques. We investigated the efficacy of these NP adjuvants in inducing protective immunity against simian immunodeficiency virus (SIV). Rhesus macaques (RMs) were immunized with NP containing TLR4 and TLR7/8 agonists mixed with soluble recombinant SIVmac239 derived envelope (Env) gp140 and Gag p55 (Protein), or with virus like particles (VLP) containing SIVmac239 Env and Gag...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27927680/functional-and-antigen-specific-serum-antibody-levels-as-correlates-of-protection-against-shigellosis-in-a-controlled-human-challenge-study
#20
Avital A Shimanovich, Amanda D Buskirk, Shannon J Heine, William C Blackwelder, Rezwanul Wahid, Karen L Kotloff, Marcela F Pasetti
Shigella is an important cause of diarrheal disease in young children living in developing countries. No approved vaccines are available, and the development of vaccine candidates has been hindered, among other reasons, by the lack of firm immunological correlates of protection. To address this gap in knowledge, we established quantitative assays to measure Shigella-specific serum bactericidal (SBA) and opsonophagocytic killing antibody (OPKA) activity and investigated their potential association with protection against disease in humans...
December 7, 2016: Clinical and Vaccine Immunology: CVI
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