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https://www.readbyqxmd.com/read/28237943/kinome-profiling-identifies-druggable-targets-for-novel-hcmv-antivirals
#1
Kyle C Arend, Erik M Lenarcic, Heather A Vincent, Naim Rashid, Eric Lazear, Ian M MacDonald, Thomas S K Gilbert, Michael P East, Laura E Herring, Gary L Johnson, Lee Graves, Nathaniel J Moorman
Human cytomegalovirus (HCMV) is a significant cause of disease in immunecompromised adults and immune naive newborns. No vaccine exists to prevent HCMV infection, and current antiviral therapies have toxic side effects that limit the duration and intensity of their use. There is thus an urgent need for new strategies to treat HCMV infection. Repurposing existing drugs as antivirals is an attractive approach to limit the time and cost of new antiviral drug development. Virus-induced changes in infected cells are often driven by changes in cellular kinase activity, which led us to hypothesize that defining the complement of kinases (the kinome), whose abundance or expression is altered during infection would identify existing kinase inhibitors that could be repurposed as new antivirals...
February 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28237837/a-novel-dna-vaccine-platform-enhances-neo-antigen-like-t-cell-responses-against-wt1-to-break-tolerance-and-induce-anti-tumor-immunity
#2
Jewell N Walters, Bernadette Ferraro, Elizabeth K Duperret, Kimberly A Kraynyak, Jaemi Chu, Ashley Saint-Fleur, Jian Yan, Hy Levitsky, Amir S Khan, Niranjan Y Sardesai, David B Weiner
Tumor-associated antigens have emerged as important immunotherapeutic targets in the fight against cancer. Germline tumor antigens, such as WT1, Wilms' tumor gene 1, are overexpressed in many human malignancies but have low expression in somatic tissues. Recent vaccination approaches to target WT1 have been hampered by poor in vivo immune potency, likely due to the conserved self-antigen nature of WT1. In this study, we use a novel synthetic micro-consensus SynCon DNA vaccine approach with the goal of breaking tolerance and increasing vaccine immune potency...
February 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28235558/dna-vaccination-regimes-against-schmallenberg-virus-infection-in-ifnar-mice-suggest-two-targets-for-immunization
#3
Hani Y Boshra, Diego Charro, Gema Lorenzo, Isbene Sanchez, Beatriz Lazaro, Alejandro Brun, Nicola G A Abrescia
Schmallenberg virus (SBV) is an RNA virus of the Bunyaviridae family, genus Orthbunyavirus, that infects wild and livestock species of ruminants. While inactivated and attenuated vaccines have been shown to prevent SBV infection, little is known about their mode of immunity; specifically, which components of the virus are responsible for inducing immunological responses in the host. As previous DNA vaccination experiments on other bunyaviruses have found that glycoproteins, as well as modified (i.e. ubiquitinated) nucleoproteins (N) can confer immunity against virulent viral challenge, constructs encoding for fragments of SBV glycoproteins GN and GC, as well as ubiquitinated and non-ubiquitinated N were cloned in mammalian expression vectors, and vaccinated intramuscularly in IFNAR(-/-) mice...
February 21, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28231660/-effect-of-telbivudine-on-infants-born-to-hbsag-positive-mothers-with-non-hypo-response-to-hepatitis-b-vaccine-during-their-second-and-third-trimesters-of-pregnancy
#4
X X Xu, B Wang, X F Wang, H X Wen, F Zhang, Z Q Yang, H Y Hao, T Wang, X H Shi, Z D Fu, B Wang, S P Wang
Objective: To explore the effect of telbivudine treatment in a prevention program on infants born to HBsAg-positive mothers with non-/hypo-responsiveness to hepatitis B vaccine. Methods: A retrospective cohort study with a total of 321 HBsAg-positive pregnant women and their infants enrolled, was conducted. The mothers were recruited from the Third People' s Hospital of Taiyuan, from July 2011 to January 2013. According to the situation of telbivudine intake in second and third trimesters of pregnancy, the participants were divided into two groups: with telbivudine-treated or as control...
February 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28231510/lipopolyplex-potentiates-anti-tumor-immunity-of-mrna-based-vaccination
#5
Stefano Persano, Maria L Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell...
February 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/28228587/prophylactic-herpes-simplex-virus-2-hsv-2-vaccines-adjuvanted-with-stable-emulsion-and-toll-like-receptor-9-agonist-induce-a-robust-hsv-2-specific-cell-mediated-immune-response-protect-against-symptomatic-disease-and-reduce-the-latent-viral-reservoir
#6
Michael T Hensel, Jason D Marshall, Michael R Dorwart, Darren S Heeke, Eileen Rao, Padmaja Tummala, Li Yu, Gary H Cohen, Roselyn J Eisenberg, Derek D Sloan
Several prophylactic vaccines targeting HSV-2 have failed in the clinic to demonstrate a sustained depression in viral shedding or protection from recurrences. Although these vaccines have generated high titers of neutralizing antibodies, their induction of robust CD8 T cells has largely been unreported, even though evidence for the importance of HSV-2 antigen-specific CD8 T cells is mounting in animal models and in translational studies involving subjects with active HSV-2-specific immune responses. We developed a subunit vaccine composed of the neutralizing antibody (nAb) targets gD and gB, the novel T cell antigen and tegument protein UL40, and we compared this to a whole-inactivated virus vaccine (FI-HSV-2)...
February 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28225652/dna-vaccination-partially-protects-muskellunge-against-viral-hemorrhagic-septicemia-virus-vhsv-ivb
#7
Elena V Millard, Ashley M Bourke, Scott E LaPatra, Travis O Brenden, Scott D Fitzgerald, Mohamed Faisal
A DNA vaccine containing the glycoprotein (G) gene of the North American viral hemorrhagic septicemia virus (VHSV) genotype IVb was developed to evaluate the immune response of fish following vaccination and evaluate its efficacy in protecting a susceptible species, the Muskellunge Esox masquinongy, against VHSV-IVb challenge. Seven weeks (539 degree-days) following vaccination with 10 μg of either pVHSivb-G or a control plasmid, Muskellunge were challenged by immersion with 10(5) plaque-forming units (pfu)/mL of VHSV-IVb...
March 2017: Journal of Aquatic Animal Health
https://www.readbyqxmd.com/read/28224119/vesicular-stomatitis-virus-vectored-multi-antigen-tuberculosis-vaccine-limits-bacterial-proliferation-in-mice-following-a-single-intranasal-dose
#8
Ming Zhang, Chunsheng Dong, Sidong Xiong
Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28223987/dendritic-cell-targeting-effectively-boosts-t-cell-responses-elicited-by-an-hiv-multiepitope-dna-vaccine
#9
Juliana de Souza Apostólico, Victória Alves Santos Lunardelli, Marcio Massao Yamamoto, Higo Fernando Santos Souza, Edecio Cunha-Neto, Silvia Beatriz Boscardin, Daniela Santoro Rosa
Despite several efforts in the last decades, an efficacious HIV-1 vaccine is still not available. Different approaches have been evaluated, such as recombinant proteins, viral vectors, DNA vaccines, and, most recently, dendritic cell (DC) targeting. This strategy is based on DC features that place them as central for induction of immunity. Targeting is accomplished by the use of chimeric monoclonal antibodies directed to DC surface receptors fused to the antigen of interest. In this work, we targeted eight promiscuous HIV-derived CD4(+) T cell epitopes (HIVBr8) to the DEC205(+) DCs by fusing the multiepitope immunogen to the heavy chain of αDEC205 (αDECHIVBr8), in the presence of the TLR3 agonist poly (I:C)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28222511/evaluation-of-a-dna-a%C3%AE-42-vaccine-in-aged-nzw-rabbits-antibody-kinetics-and-immune-profile-after-intradermal-immunization-with-full-length-dna-a%C3%AE-42-trimer
#10
Doris Lambracht-Washington, Min Fu, Mary Wight-Carter, Matthew Riegel, Roger N Rosenberg
A pathological hallmark of Alzheimer's disease (AD) are amyloid plaques in the brain consisting of aggregated amyloid-β 42 peptide (Aβ42) derived from cellular amyloid-β protein precursor (AβPP). Based on successful experiments in mouse AD models, active immunization with Aβ42 peptide and passive immunizations with anti-Aβ42 antibodies were started in clinical trials. Active Aβ42 peptide immunization in humans had led to an inflammatory autoimmune response, and the trial was stopped. Passive immunizations had shown some effects in slowing AD pathology...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28221100/intracellular-degradation-and-localization-of-ns1-of-tick-borne-encephalitis-virus-affect-its-protective-properties
#11
Yulia V Kuzmenko, Elizaveta S Starodubova, Anastasia S Shevtsova, Liubov L Chernokhaeva, Anastasia A Latanova, Olga V Preobrazhenskaia, Andrey V Timofeev, Galina G Karganova, Vadim L Karpov
Currently, many DNA vaccines against infectious diseases are in clinical trials; however, their efficacy needs to be improved. The potency of DNA immunogen can be optimized by targeting technologies. In the current study, to increase the efficacy of NS1 encoded by plasmid, proteasome targeting was applied. NS1 variants with or without translocation sequence and with ornithine decarboxylase as a signal of proteasomal degradation were tested for expression, localization, protein turnover, proteasomal degradation and protection properties...
January 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28219022/rationale-for-stimulator-of-interferon-genes-targeted-cancer-immunotherapy
#12
REVIEW
Thaiz Rivera Vargas, Isis Benoit-Lizon, Lionel Apetoh
The efficacy of checkpoint inhibitor therapy illustrates that cancer immunotherapy, which aims to foster the host immune response against cancer to achieve durable anticancer responses, can be successfully implemented in a routine clinical practice. However, a substantial proportion of patients does not benefit from this treatment, underscoring the need to identify alternative strategies to defeat cancer. Despite the demonstration in the 1990's that the detection of danger signals, including the nucleic acids DNA and RNA, by dendritic cells (DCs) in a cancer setting is essential for eliciting host defence, the molecular sensors responsible for recognising these danger signals and eliciting anticancer immune responses remain incompletely characterised, possibly explaining the disappointing results obtained so far upon the clinical implementation of DC-based cancer vaccines...
February 17, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28216094/fusion-of-flagellin-2-with-bivalent-white-spot-syndrome-virus-vaccine-increases-survival-in-freshwater-shrimp
#13
Hansam Cho, Na Hye Park, Yuyeon Jang, Yong-Dae Gwon, Yeondong Cho, Yoon-Ki Heo, Ki-Hoon Park, Hee-Jung Lee, Tae Jin Choi, Young Bong Kim
Despite large economic losses attributable to white spot syndrome virus (WSSV), an infectious pathogen of penaeid shrimp and other crustaceans worldwide, no efficient vaccines or antiviral agents to control the virus are available at present. Here, we designed and constructed baculovirus-based vaccines delivering genes encoding the WSSV envelope proteins, VP28 and VP19. To enhance the immunogenicity of the baculovirus-based vaccine, we fused a Salmonella typhimurium flagellin 2 (FL2) gene with VP28 or VP19 gene...
February 16, 2017: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/28213262/one-single-fast-and-robust-capillary-electrophoresis-method-for-the-direct-quantification-of-intact-adenovirus-particles-in-upstream-and-downstream-processing-samples
#14
Ewoud van Tricht, Lars Geurink, Harold Backus, Marta Germano, Govert W Somsen, Cari E Sänger-van de Griend
During development of adenovirus-based vaccines, samples have to be analyzed in order to either monitor the production process or control the quality and safety of the product. An important quality attribute is the total concentration of intact adenoviruses, which currently is determined by quantitative polymerase chain reaction (qPCR) or anion exchange-HPLC. Capillary Electrophoresis (CE) was evaluated as alternative to the current methods with the aim to have one single method that allows reliable and fast quantification of adenovirus particles throughout the full process...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28212457/papillomaviruses-a-systematic-review
#15
Rodrigo Pinheiro Araldi, Suely Muro Reis Assaf, Rodrigo Franco de Carvalho, Márcio Augusto Caldas Rocha de Carvalho, Jacqueline Mazzuchelli de Souza, Roberta Fiusa Magnelli, Diego Grando Módolo, Franco Peppino Roperto, Rita de Cassia Stocco, Willy Beçak
In the last decades, a group of viruses has received great attention due to its relationship with cancer development and its wide distribution throughout the vertebrates: the papillomaviruses. In this article, we aim to review some of the most relevant reports concerning the use of bovines as an experimental model for studies related to papillomaviruses. Moreover, the obtained data contributes to the development of strategies against the clinical consequences of bovine papillomaviruses (BPV) that have led to drastic hazards to the herds...
February 16, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28211908/the-n-terminal-domain-of-schmallenberg-virus-envelope-protein-gc-is-highly-immunogenic-and-can-provide-protection-from-infection
#16
Kerstin Wernike, Andrea Aebischer, Gleyder Roman-Sosa, Martin Beer
Schmallenberg virus (SBV) is transmitted by insect vectors, and therefore vaccination is one of the most important tools of disease control. In our study, novel subunit vaccines on the basis of an amino-terminal domain of SBV Gc of 234 amino acids ("Gc Amino") first were tested and selected using a lethal small animal challenge model and then the best performing formulations also were tested in cattle. We could show that neither E. coli expressed nor the reduced form of "Gc Amino" protected from SBV infection...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210460/cloning-and-expression-of-clostridium-perfringens-type-d-vaccine-strain-epsilon-toxin-gene-in-e-coli-as-a-recombinant-vaccine-candidate
#17
Parastoo Aziminia, Reza Pilehchian-Langroudi, Kasra Esmaeilnia
BACKGROUND AND OBJECTIVES: Clostridium perfringens, a Gram-positive obligate anaerobic bacterium, is able to form resistant spores which are widely distributed in the environment. C. perfringens is subdivided into five types A to E based on its four major alpha, beta, epsilon and iota toxins. The aim of the present study was cloning and expression of C. perfringens type D vaccine strain epsilon toxin gene. MATERIALS AND METHODS: Genomic DNA was extracted and the epsilon toxin gene was amplified using Pfu DNA polymerase...
August 2016: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/28209186/identification-of-immune-protective-genes-of-eimeria-maxima-through-cdna-expression-library-screening
#18
XinChao Yang, MengHui Li, JianHua Liu, YiHong Ji, XiangRui Li, LiXin Xu, RuoFeng Yan, XiaoKai Song
BACKGROUND: Eimeria maxima is one of the most prevalent Eimeria species causing avian coccidiosis, and results in huge economic loss to the global poultry industry. Current control strategies, such as anti-coccidial medication and live vaccines have been limited because of their drawbacks. The third generation anticoccidial vaccines including the recombinant vaccines as well as DNA vaccines have been suggested as a promising alternative strategy. To date, only a few protective antigens of E...
February 16, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28204975/surface-and-exoproteomes-of-gram-positive-pathogens-for-vaccine-discovery
#19
Massimiliano Biagini, Fabio Bagnoli, Nathalie Norais
Reverse vaccinology has been very successful in the discovery of vaccine candidates against many pathogenic bacteria by integrating genome and proteome mining. This great achievement was facilitated by the complementarity of the in silico prediction of antigens and the empirical data on protein localization, expression, and immunogenicity obtained through different techniques based on electrophoresis, immunoblotting and mass spectrometry. An iterative process between information provided by DNA sequence analysis and proteomic data has been established leading to precise antigen identification...
February 16, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28202760/restriction-of-hcmv-replication-by-isg15-a-host-effector-regulated-by-cgas-sting-dsdna-sensing
#20
Christopher Bianco, Ian Mohr
Accumulation of the interferon-stimulated gene (ISG) 15 protein product, which is reversibly conjugated to numerous polypeptide targets, impacts the proteome and physiology of uninfected and infected cells. While many viruses, including human cytomegalovirus (HCMV) blunt host antiviral defenses by limiting ISG expression, the overall abundance of ISG15 monomer and protein conjugates rises in HCMV-infected cells. However, the molecular signals underlying ISG15 accumulation and whether the ISG15 polypeptide itself influences HCMV infection biology remain unknown...
February 15, 2017: Journal of Virology
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