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https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#1
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep M ª Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector employs an antibiotic resistance-free mechanism for plasmid selection and maintenance...
April 20, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28424330/combination-of-an-oncolytic-virus-with-pd-l1-blockade-keeps-cancer-in-check
#2
Brian A Jonas
An oncolytic vaccinia virus expressing CXCL11 combined with PD-L1 blockade significantly reduces tumor burden and improves survival in murine cancer models.
April 19, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28424281/distinct-roles-of-vaccinia-virus-nf-kb-inhibitor-proteins-a52-b15-and-k7-in-the-immune-response
#3
Mauro Di Pilato, Ernesto Mejías-Pérez, Carlos Oscar S Sorzano, Mariano Esteban
Poxviruses use a complex strategy to escape immune control, by expressing immunomodulatory proteins that could limit their use as vaccine vectors. To test the role of poxvirus NF-κB pathway inhibitors A52, B15 and K7 in immunity, we deleted their genes in a NYVAC vaccinia virus strain that expresses HIV-1 clade C antigens. After infection of mice, ablation of A52R, B15R and K7R increased dendritic cell, natural killer cell and neutrophil migration as well as chemokine/cytokine expression. Revertant viruses for these genes confirmed their role in inhibiting the innate immune system...
April 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28422752/t-bet-b-cells-are-induced-by-human-viral-infections-and-dominate-the-hiv-gp140-response
#4
James J Knox, Marcus Buggert, Lela Kardava, Kelly E Seaton, Michael A Eller, David H Canaday, Merlin L Robb, Mario A Ostrowski, Steven G Deeks, Mark K Slifka, Georgia D Tomaras, Susan Moir, M Anthony Moody, Michael R Betts
Humoral immunity is critical for viral control, but the identity and mechanisms regulating human antiviral B cells are unclear. Here, we characterized human B cells expressing T-bet and analyzed their dynamics during viral infections. T-bet+ B cells demonstrated an activated phenotype, a distinct transcriptional profile, and were enriched for expression of the antiviral immunoglobulin isotypes IgG1 and IgG3. T-bet+ B cells expanded following yellow fever virus and vaccinia virus vaccinations and also during early acute HIV infection...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28412365/vaccinia-related-kinase-3-vrk3-sets-the-circadian-period-and-amplitude-by-affecting-the-subcellular-localization-of-clock-proteins-in-mammalian-cells
#5
Nayoung Park, Ji-Eun Song, Seongsu Jeong, Thanh Thi Tran, Hyuk Wan Ko, Eun Young Kim
In the eukaryotic circadian clock machinery, negative feedback repression of CLOCK (CLK) and BMAL1 transcriptional activity by PERIOD (PER) and CRYPTOCHROME (CRY) underlies the basis for 24 h rhythmic gene expression. Thus, precise regulation of the time-dependent nuclear entry of circadian repressors is crucial to generating normal circadian rhythms. Here, we sought to identify novel kinase(s) that regulate nuclear entry of mammalian CRY1 (mCRY1) with an unbiased screening using red fluorescent protein (RFP)-tagged human kinome expression plasmids in mammalian cells...
April 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28405630/efficient-and-robust-paramyxoviridae-reverse-genetics-systems
#6
Shannon M Beaty, Arnold Park, Sohui T Won, Patrick Hong, Michael Lyons, Frederic Vigant, Alexander N Freiberg, Benjamin R tenOever, W Paul Duprex, Benhur Lee
The notoriously low efficiency of Paramyxoviridae reverse genetics systems has posed a limiting barrier to the study of viruses in this family. Previous approaches to reverse genetics have utilized a wide variety of techniques to overcome the technical hurdles. Although robustness (i.e., the number of attempts that result in successful rescue) has been improved in some systems with the use of stable cell lines, the efficiency of rescue (i.e., the proportion of transfected cells that yield at least one successful rescue event) has remained low...
March 2017: MSphere
https://www.readbyqxmd.com/read/28405614/il-21-is-required-for-cd4-memory-formation-in-response-to-viral-infection
#7
Yuqing Yuan, Yiping Yang, Xiaopei Huang
IL-21 has been shown to play an important role in the CD8 T cell response during acute and chronic viral infections. However, the role of IL-21 signaling in the CD4 T cell response to viral infection remains incompletely defined. In a model of infection with vaccinia virus, we show that intrinsic IL-21 signaling on CD4 T cells was critical for the formation of memory CD4 T cells in vivo. We further reveal that IL-21 promoted CD4 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 signaling pathways...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28403810/transient-dominant-host-range-selection-using-chinese-hamster-ovary-cells-to-generate-marker-free-recombinant-viral-vectors-from-vaccinia-virus
#8
Liang Liu, Tamara Cooper, Preethi Eldi, Pablo Garcia-Valtanen, Kerrilyn R Diener, Paul M Howley, John D Hayball
Recombinant vaccinia viruses (rVACVs) are promising antigen-delivery systems for vaccine development that are also useful as research tools. Two common methods for selection during construction of rVACV clones are (i) co-insertion of drug resistance or reporter protein genes, which requires the use of additional selection drugs or detection methods, and (ii) dominant host-range selection. The latter uses VACV variants rendered replication-incompetent in host cell lines by the deletion of host-range genes. Replicative ability is restored by co-insertion of the host-range genes, providing for dominant selection of the recombinant viruses...
April 1, 2017: BioTechniques
https://www.readbyqxmd.com/read/28395583/isolation-and-identification-of-compounds-from-kalanchoe-pinnata-having-human-alphaherpesvirus-and-vaccinia-virus-antiviral-activity
#9
Matthew Cryer, Kyle Lane, Mary Greer, Rex Cates, Scott Burt, Merritt Andrus, Jiping Zou, Paul Rogers, Marc D H Hansen, Jillybeth Burgado, Subbian Satheshkumar Panayampalli, Craig W Day, Donald F Smee, Brent F Johnson
CONTEXT: Kalanchoe pinnata (Lam.) Pers. (Crassulaceae) is a succulent plant that is known for its traditional antivirus and antibacterial usage. OBJECTIVE: This work examines two compounds identified from the K. pinnata plant for their antivirus activity against human alphaherpesvirus (HHV) 1 and 2 and vaccinia virus (VACV). MATERIALS AND METHODS: Compounds KPB-100 and KPB-200 were isolated using HPLC and were identified using NMR and MS. Both compounds were tested in plaque reduction assay of HHV-2 wild type (WT) and VACV...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28389806/absence-of-vaccinia-virus-detection-in-a-remote-region-of-the-northern-amazon-forests-2005-2015
#10
Galileu Barbosa Costa, Anne Lavergne, Edith Darcissac, Vincent Lacoste, Betânia Paiva Drumond, Jônatas Santos Abrahão, Erna Geessien Kroon, Benoît de Thoisy, Giliane de Souza Trindade
Vaccinia virus (VACV) circulates in Brazil and other South America countries and is responsible for a zoonotic disease that usually affects dairy cattle and humans, causing economic losses and impacting animal and human health. Furthermore, it has been detected in wild areas in the Brazilian Amazon. To better understand the natural history of VACV, we investigated its circulation in wildlife from French Guiana, a remote region in the Northern Amazon forest. ELISA and plaque reduction neutralization tests were performed to detect anti-orthopoxvirus antibodies...
April 7, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28383204/monocytic-myeloid-derived-suppressor-cells-regulate-t-cell-responses-against-vaccinia-virus
#11
Carl Fortin, Yiping Yang, Xiaopei Huang
Vaccinia virus (VV) can potently activate NK- and T-cell responses, leading to efficient viral control and generation of long-lasting protective immunity. However, immune responses against viral infections are often tightly controlled to avoid collateral damage and systemic inflammation. We have previously shown that granulocytic myeloid derived suppressor cells (g-MDSCs) can suppress the NK-cell response to VV infection. It remains unknown what regulates T-cell responses to VV infection in vivo. In this study, we first showed that monocytic MDSCs (m-MDSCs), but not g-MDSCs, from VV-infected mice could directly suppress CD4(+) and CD8(+) T-cell activation in vitro...
April 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28374246/poxvirus-safety-analysis-in-the-pregnant-mouse-model-vaccinia-and-raccoonpox-viruses
#12
Rachel L Roper
Poxviruses cause many diseases in humans and animals worldwide, and there is a need for vaccines with improved safety and good efficacy. In addition, poxvirus vectors are widely used as recombinant vaccines for various infectious diseases and as recombinant and oncolytic vaccines for cancer. One concern with poxvirus vaccine vectors is that some poxviruses can infect a developing fetus and cause fetal loss or congenital disease. This can be an issue both for patients receiving a vaccine and for pregnant health care providers, including doctors, nurses, and veterinarians, who might receive accidental exposure to the poxvirus by injection or during patient care...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28374245/generation-and-production-of-modified-vaccinia-virus-ankara-mva-as-a-vaccine-vector
#13
Vincent Pavot, Sarah Sebastian, Alison V Turner, Jake Matthews, Sarah C Gilbert
The smallpox vaccine based on the vaccinia virus was successfully used to eradicate smallpox, but although very effective, it was a very reactogenic vaccine and responsible for the deaths of one to two people per million vaccinated. Modified Vaccinia virus Ankara (MVA) is an attenuated derivative, also used in the smallpox eradication campaign and now being developed as a recombinant viral vector to produce vaccines against infectious diseases and cancer. MVA can encode one or more foreign antigens and thus can function as a multivalent vaccine...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28374241/development-of-recombinant-canarypox-viruses-expressing-immunogens
#14
Débora Garanzini, María Paula Del Médico-Zajac, Gabriela Calamante
Canarypox viruses (CNPV) are excellent candidates to develop recombinant vector vaccines due to both their capability to induce protective immune responses and their incompetence to replicate in mammalian cells (safety profile). In addition, CNPV and the derived recombinants can be manipulated under biosafety level 1 conditions. There is no commercially available system to obtain recombinant CNPV; however, the methodology and tools required to develop recombinant vaccinia virus (VV), prototype of the Poxviridae family, can be easily adapted...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28370198/diclofenac-based-hydrazones-and-spirothiazolidinones-synthesis-characterization-and-antimicrobial-properties
#15
Ayşe Kocabalkanlı, Gökçe Cihan-Üstündağ, Lieve Naesens, Emel Mataracı-Kara, Mebble Nassozi, Gültaze Çapan
We report here the synthesis, structural characterization, and biological evaluation of novel diclofenac-based hydrazone (4a-f) and spirothiazolidinone (5a-f, 6a-f) derivatives designed as potential antimicrobial agents. The compounds were evaluated in vitro for their antiviral activity against a wide spectrum of DNA and RNA viruses. They were further screened in vitro against different strains of bacteria and fungi. The hydrazone derivatives, 4a and 4c-f, were found to be active against herpesviruses (HSV-1, HSV-2, and HSV-1 TK(-) ), vaccinia virus, and Coxsackie B4 virus, with EC50 values between 6...
March 30, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28366604/single-n277a-substitution-in-c2-of-simian-immunodeficiency-virus-envelope-influences-vaccine-elicited-cd4i-neutralizing-and-anti-v2-antibody-responses
#16
Xian Tang, Jia Guo, Lin Cheng, Caijun Sun, Li Liu, Teng Zuo, Hui Wang, Ling Chen, Linqi Zhang, Zhiwei Chen
An effective HIV vaccine remains elusive, and immunogens capable of eliciting protective host humoral immunity have not yet been identified. Although HIV/SIV infections result in the abundant production of CD4-induced (CD4i) antibodies (Abs), these Abs are not protective due to steric restrictions following gp120 binding to CD4 on target cells. Here we report that both DNA- and vaccinia-based vaccines encoding SIVmac239 gp160 readily elicited high levels of CD4i Abs in experimental animals. We identified a highly conserved N-linked glycosylation site N277 in the C2 region which strongly affected the immunogenicity of the CD4i Ab domain...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28366525/vaccinia-virus-evasion-of-regulated-cell-death
#17
REVIEW
David L Veyer, Guia Carrara, Carlos Maluquer de Motes, Geoffrey L Smith
Regulated cell death is a powerful anti-viral mechanism capable of aborting the virus replicative cycle and alerting neighbouring cells to the threat of infection. The biological importance of regulated cell death is illustrated by the rich repertoire of host signalling cascades causing cell death and by the multiple strategies exhibited by viruses to block death signal transduction and preserve cell viability. Vaccinia virus (VACV), a poxvirus and the vaccine used to eradicate smallpox, encodes multiple proteins that interfere with apoptotic, necroptotic and pyroptotic signalling...
March 30, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28363906/varied-role-of-ubiquitylation-in-generating-mhc-class-i-peptide-ligands
#18
Jiajie Wei, Damien Zanker, Anthony R Di Carluccio, Margery G Smelkinson, Kazuyo Takeda, Mina O Seedhom, Devin Dersh, James S Gibbs, Ning Yang, Ajit Jadhav, Weisan Chen, Jonathan W Yewdell
CD8(+) T cell immunosurveillance is based on recognizing oligopeptides presented by MHC class I molecules. Despite decades of study, the importance of protein ubiquitylation to peptide generation remains uncertain. In this study, we examined the ability of MLN7243, a recently described ubiquitin-activating enzyme E1 inhibitor, to block overall cytosolic peptide generation and generation of specific peptides from vaccinia- and influenza A virus-encoded proteins. We show that MLN7243 rapidly inhibits ubiquitylation in a variety of cell lines and can profoundly reduce the generation of cytosolic peptides...
March 31, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28359239/oncolytic-virotherapy-and-gene-therapy-strategies-for-hepatobiliary-cancers
#19
Takeshi Yamada, Yukako Hamano, Naoyuki Hasegawa, Kazunari K Yokoyama, Ichinosuke Hyodo, Masato Abei
Advanced liver cancers and biliary cancers represent diseases with dismal prognosis because of frequent local invasion and metastasis. Effective therapeutic agents for these cancers have not been established. Oncolytic viruses (OVs) constitute a novel class of promising, selective anticancer agents and recent studies have elucidated their unique features. Moreover, clinical trials are demonstrating promising results. Numerous OVs are being tested in preclinical models of hepatocellular carcinoma (HCC). The lead agent Pexa-Vec (pexastimogene devacirepvec, JX-594) , a recombinant Wyeth strain vaccinia virus, has demonstrated preliminary evidence of safety and efficacy for HCC in clinical trials...
March 30, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28359234/identification-of-novel-5-6-dimethoxyindan-1-one-derivatives-as-antiviral-agents
#20
Siddappa A Patil, Vikrant Patil, Renukadevi Patil, Kenneth Beaman, Shivaputra A Patil
BACKGROUND: Discovery of novel antiviral agents is essential because viral infection continues to threaten human life globally. Various heterocyclic small molecules have been developed as antiviral agents. The 5,6-dimethoxy indan-1-one nucleus is of considerable interest as this ring is the key constituent in a range of bioactive compounds, both naturally occurring and synthetic, and often of considerable complexity. OBJECTIVE: The main purpose of this research was to discover and develop small molecule heterocycles as broad-spectrum of antiviral agents...
March 29, 2017: Medicinal Chemistry
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