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https://www.readbyqxmd.com/read/29223787/a-novel-peptide-based-vaccine-candidate-with-protective-efficacy-against-influenza-a-in-a-mouse-model
#1
José Herrera-Rodriguez, Tjarko Meijerhof, Hubert G Niesters, Grete Stjernholm, Arnt-Ove Hovden, Birger Sørensen, Mats Ökvist, Maja A Sommerfelt, Anke Huckriede
Current influenza vaccines mainly induce antibody responses to the variable hemagglutinin proteins of the virus strains included in the vaccine. Instead, a broadly protective influenza vaccine should aim at inducing antibody- and/or cell-mediated immunity against conserved viral proteins. Vacc-FLU is a peptide based vaccine combining conserved B and T cell epitopes. Peptide selection was done using a proprietary peptide design platform technology focusing on responses to human leukocyte antigen (HLA)-restricted epitopes...
December 7, 2017: Virology
https://www.readbyqxmd.com/read/29222473/hypoxia-inducible-factor-1%C3%AE-is-essential-for-macrophage-mediated-erythroblast-proliferation-in-acute-friend-retrovirus-infection
#2
Timm Schreiber, Theresa Quinting, Ulf Dittmer, Joachim Fandrey, Kathrin Sutter
Macrophages are the frontline of defence against foreign microorganisms, including bacteria, parasites, and viruses. During acute viral infection, macrophages must invade the inflamed tissue toward low oxygen concentrations, where genetic cellular responses depend on hypoxia-inducible factors (HIF). In the study reported here we investigated the role of HIF-1α in macrophage function during acute retroviral infection. Wild-type and myeloid cell-specific HIF-1α knockout mice were infected with Friend retrovirus (FV), and immune response was analysed 7 and 10 days after infection...
December 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29222166/effect-of-il-7-therapy-on-phospho-ribosomal-protein-s6-and-traf1-expression-in-hiv-specific-cd8-t-cells-in-patients-receiving-antiretroviral-therapy
#3
Chao Wang, Maria I Edilova, Lisa E Wagar, Shariq Mujib, Meromit Singer, Nicole F Bernard, Thérèse Croughs, Michael M Lederman, Irini Sereti, Margaret A Fischl, Elisabeth Kremmer, Mario Ostrowski, Jean-Pierre Routy, Tania H Watts
IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice...
December 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29221181/analysis-of-ctcl-cell-lines-reveals-important-differences-between-mycosis-fungoides-s%C3%A3-zary-syndrome-vs-htlv-1-leukemic-cell-lines
#4
Elena Netchiporouk, Jennifer Gantchev, Matthew Tsang, Philippe Thibault, Andrew K Watters, John-Douglas Matthew Hughes, Feras M Ghazawi, Anders Woetmann, Niels Ødum, Denis Sasseville, Ivan V Litvinov
HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220721/novel-effect-of-methionine-enkephalin-against-influenza-a-virus-infection-through-inhibiting-tlr7-myd88-traf6-nf-%C3%AE%C2%BAb-p65-signaling-pathway
#5
Jing Tian, Xue Jiao, Xiaonan Wang, Jin Geng, Reizhe Wang, Ning Liu, Xinhua Gao, Noreen Griffin, Fengping Shan
The morbidity and mortality associated with influenza A virus infections, have stimulated the search for novel prophylactic and therapeutic drugs. The purpose of this study was to investigate the prophylactic and therapeutic effect of synthetic methionine enkephalin (MENK) on mice infected by A/PR/8/34 influenza virus (H1N1) in vivo. The results showed that MENK could exert both prophylactic and therapeutic influences on infected mice, significantly improve the survival rate, relieve acute lung injury and decrease cytokine (IFN-α, IFN-β, TNF-α, IL-6, and IL-1β) levels...
December 5, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29220404/pymt-maclow-a-novel-inducible-murine-model-for-determining-the-role-of-cd68-positive-cells-in-breast-tumor-development
#6
Robin M H Rumney, Seth B Coffelt, Terence A Neale, Sandeep Dhayade, Gillian M Tozer, Gaynor Miller
CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development...
2017: PloS One
https://www.readbyqxmd.com/read/29218825/in-vivo-evidence-supporting-a-metastasis-suppressor-role-for-stard13-dlc2-in-erbb2-neu-oncogene-induced-mouse-mammary-tumours
#7
Pratima Basak, Heather Leslie, Rachelle L Dillon, William J Muller, Afshin Raouf, Michael Ra Mowat
Overexpression of dominant oncogenes and the loss of tumor suppressor genes are basic genetic events in the acquisition of the malignant phenotype. The erb-b2 receptor tyrosine kinase 2 (ERBB-2) proto-oncogene is overexpressed in 20-30% of human breast cancers. The StAR related lipid transfer domain containing 13 gene (STARD13), also known as Deleted in Liver Cancer-2 (DLC-2), maps to chromosome band 13q12.3 and is frequently downregulated in human cancers, including 72% of breast cancers. It encodes a RhoGAP protein with sterile α motif (SAM) and StAR-related lipid transfer (START) domains...
December 8, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29217749/hepatitis-delta-virus-persists-during-liver-regeneration-and-is-amplified-through-cell-division-both-in-vitro-and-in-vivo
#8
Katja Giersch, Oliver D Bhadra, Tassilo Volz, Lena Allweiss, Kristoffer Riecken, Boris Fehse, Ansgar W Lohse, Joerg Petersen, Camille Sureau, Stephan Urban, Maura Dandri, Marc Lütgehetmann
OBJECTIVE: Hepatitis delta virus (HDV) was shown to persist for weeks in the absence of HBV and for months after liver transplantation, demonstrating the ability of HDV to persevere in quiescent hepatocytes. The aim of the study was to evaluate the impact of cell proliferation on HDV persistence in vitro and in vivo. DESIGN: Genetically labelled human sodium taurocholate cotransporting polypeptide (hNTCP)-transduced human hepatoma(HepG2) cells were infected with HBV/HDV and passaged every 7 days for 100 days in the presence of the entry inhibitor Myrcludex-B...
December 7, 2017: Gut
https://www.readbyqxmd.com/read/29217660/chimeric-pneumoviridae-fusion-proteins-as-immunogens-to-induce-cross-neutralizing-antibody-responses
#9
Eduardo Olmedillas, Olga Cano, Isidoro Martínez, Daniel Luque, María C Terrón, Jason S McLellan, José A Melero, Vicente Más
Human respiratory syncytial virus (hRSV) and human metapneumovirus (hMPV), two members of the Pneumoviridae family, account for the majority of severe lower respiratory tract infections worldwide in very young children. They are also a frequent cause of morbidity and mortality in the elderly and immunocompromised adults. High levels of neutralizing antibodies, mostly directed against the viral fusion (F) glycoprotein, correlate with protection against either hRSV or hMPV However, no cross-neutralization is observed in polyclonal antibody responses raised after virus infection or immunization with purified F proteins...
December 7, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29217375/preliminary-aggregate-safety-and-immunogenicity-results-from-three-trials-of-a-purified-inactivated-zika-virus-vaccine-candidate-phase-1-randomised-double-blind-placebo-controlled-clinical-trials
#10
Kayvon Modjarrad, Leyi Lin, Sarah L George, Kathryn E Stephenson, Kenneth H Eckels, Rafael A De La Barrera, Richard G Jarman, Erica Sondergaard, Janice Tennant, Jessica L Ansel, Kristin Mills, Michael Koren, Merlin L Robb, Jill Barrett, Jason Thompson, Alison E Kosel, Peter Dawson, Andrew Hale, C Sabrina Tan, Stephen R Walsh, Keith E Meyer, James Brien, Trevor A Crowell, Azra Blazevic, Karla Mosby, Rafael A Larocca, Peter Abbink, Michael Boyd, Christine A Bricault, Michael S Seaman, Anne Basil, Melissa Walsh, Veronica Tonwe, Daniel F Hoft, Stephen J Thomas, Dan H Barouch, Nelson L Michael
BACKGROUND: A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings. METHODS: We did three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three studies, healthy adults were randomly assigned by a computer-generated list to receive 5 μg ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center, Boston, MA, USA...
December 4, 2017: Lancet
https://www.readbyqxmd.com/read/29216863/ccl5-ccr5-interactions-modulate-metabolic-events-during-tumor-onset-to-promote-tumorigenesis
#11
Darrin Gao, Lisa H Cazares, Eleanor N Fish
BACKGROUND: In earlier studies we have shown that CCL5 activation of CCR5 induces the proliferation and survival of breast cancer cells in a mechanistic target of rapamycin (mTOR)-dependent manner and that this is in part due to CCR5-mediated increases in glycolytic metabolism. METHODS: Using the MDA-MB-231 triple negative human breast cancer cell line and mouse mammary tumor virus - polyomavirus middle T-antigen (MMTV-PyMT) mouse primary breast cancer cells, we conducted in vivo tumor transplant experiments to examine the effects of CCL5-CCR5 interactions in the context of regulating tumor metabolism...
December 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29216507/chimeric-hcmv-hsv-1-and-%C3%AE-%C3%AE-134-5-oncolytic-herpes-simplex-virus-elicit-immune-mediated-antigliomal-effect-and-antitumor-memory
#12
Mohammed G Ghonime, Josh Jackson, Amish Shah, Justin Roth, Mao Li, Ute Saunders, Jennifer Coleman, G Yancey Gillespie, James M Markert, Kevin A Cassady
Malignant gliomas are the most common primary brain tumor and are characterized by rapid and highly invasive growth. Because of their poor prognosis, new therapeutic strategies are needed. Oncolytic virotherapy (OV) is a promising strategy for treating cancer that incorporates both direct viral replication mediated and immune mediated mechanisms to kill tumor cells. C134 is a next generation Δγ134.5 oHSV-1 with improved intratumoral viral replication. It remains safe in the CNS environment by inducing early IFN signaling which restricts its replication in non-malignant cells...
December 4, 2017: Translational Oncology
https://www.readbyqxmd.com/read/29216362/an-hsv-2-single-cycle-candidate-vaccine-deleted-in-glycoprotein-d-%C3%AE-gd-2-protects-male-mice-from-lethal-skin-challenge-with-clinical-isolates-of-hsv-1-and-hsv-2
#13
Clare Burn, Natalie Ramsey, Scott J Garforth, Steven Almo, William R Jacobs, Betsy C Herold
HSV infections manifest as recurrent oral or genital mucosal lesions, meningoencephalitis, corneal blindness and perinatal disease. Subunit vaccines have advanced into the clinic without success. None were tested preclinically in male mice. We compared a single-cycle candidate vaccine deleted in HSV-2 glycoprotein D (ΔgD-2) and subunit gD-2 or gD-1 protein vaccines in a male murine skin model. ΔgD-2 provided complete protection against 10-times the lethal dose of HSV-1 or HSV-2 clinical isolates and no latent virus was detected, whereas gD-1 and gD-2 adjuvanted proteins provided little or no protection...
December 5, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29216187/a-thermostable-messenger-rna-based-vaccine-against-rabies
#14
Lothar Stitz, Annette Vogel, Margit Schnee, Daniel Voss, Susanne Rauch, Thorsten Mutzke, Thomas Ketterer, Thomas Kramps, Benjamin Petsch
Although effective rabies virus vaccines have been existing for decades, each year, rabies virus infections still cause around 50.000 fatalities worldwide. Most of these cases occur in developing countries, where these vaccines are not available. The reasons for this are the prohibitive high costs of cell culture or egg grown rabies virus vaccines and the lack of a functional cold chain in many regions in which rabies virus is endemic. Here, we describe the excellent temperature resistance of a non-replicating mRNA based rabies virus vaccine encoding the rabies virus glycoprotein (RABV-G)...
December 7, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29214495/comparison-of-anti-influenza-virus-activity-and-pharmacokinetics-of-oseltamivir-free-base-and-oseltamivir-phosphate
#15
Jin Soo Shin, Keun Bon Ku, Yejin Jang, Yi-Seul Yoon, Daeho Shin, Oh Seung Kwon, Yun Young Go, Seong Soon Kim, Myoung Ae Bae, Meehyein Kim
Influenza viruses are major human respiratory pathogens that cause high morbidity and mortality worldwide. Currently, prophylactic vaccines and therapeutic antiviral agents are used to prevent and control influenza virus infection. Oseltamivir free base (OSV-FB), a modified generic antiviral drug of Tamiflu (oseltamivir phosphate, OSV-P), was launched in the Republic of Korea last year. Here, we examine the bioequivalence of these two compounds by assessing their antiviral efficacy in infected cells and in a mouse model...
December 2017: Journal of Microbiology / the Microbiological Society of Korea
https://www.readbyqxmd.com/read/29214156/off-target-effects-of-drugs-that-disrupt-human-mitochondrial-dna-maintenance
#16
REVIEW
Matthew J Young
Nucleoside reverse transcriptase inhibitors (NRTIs) were the first drugs used to treat human immunodeficiency virus (HIV) the cause of acquired immunodeficiency syndrome. Development of severe mitochondrial toxicity has been well documented in patients infected with HIV and administered NRTIs. In vitro biochemical experiments have demonstrated that the replicative mitochondrial DNA (mtDNA) polymerase gamma, Polg, is a sensitive target for inhibition by metabolically active forms of NRTIs, nucleotide reverse transcriptase inhibitors (NtRTIs)...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29213267/revealing-the-complexity-in-cd8-t-cell-responses-to-infection-in-inbred-c57b-6-versus-outbred-swiss-mice
#17
Matthew D Martin, Derek B Danahy, Stacey M Hartwig, John T Harty, Vladimir P Badovinac
Recent work has suggested that current mouse models may underrepresent the complexity of human immune responses. While most mouse immunology studies utilize inbred mouse strains, it is unclear if conclusions drawn from inbred mice can be extended to all mouse strains or generalized to humans. We recently described a "surrogate activation marker" approach that could be used to track polyclonal CD8 T cell responses in inbred and outbred mice and noted substantial discord in the magnitude and kinetics of CD8 T cell responses in individual outbred mice following infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29212937/experimental-adaptive-evolution-of-sivcpz-to-pandemic-hiv-1-using-a-humanized-mouse-model
#18
Kei Sato, Naoko Misawa, Junko S Takeuchi, Tomoko Kobayashi, Taisuke Izumi, Hirofumi Aso, Shumpei Nagaoka, Keisuke Yamamoto, Izumi Kimura, Yoriyuki Konno, Yusuke Nakano, Yoshio Koyanagi
HIV-1, the causative agent of AIDS, is originated from SIVcpz, the chimpanzee precursor of the human virus, approximately 100 years ago. This indicates that HIV-1 has emerged through the cross-species transmission of SIVcpz from chimpanzees to humans. However, it remains unclear how SIVcpz has evolved into pandemic HIV-1 in humans. To address this question, we inoculated three SIVcpz (MB897, EK505, and MT145), four pandemic HIV-1 (NL4-3, NLCSFV3, JRCSF and AD8) and 2 non-pandemic HIV-1 (YBF30 and DJO0131) strains...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212932/minor-capsid-protein-l2-polytope-induces-broad-protection-against-oncogenic-and-mucosal-human-papillomaviruses
#19
Somayeh Pouyanfard, Gloria Spagnoli, Lorenzo Bulli, Kathrin Balz, Fan Yang, Caroline Odenwald, Hanna Seitz, Filipe C Mariz, Angelo Bolchi, Simone Ottonello, Martin Müller
The amino terminus of the human papillomavirus minor capsid protein L2 contains a major cross-neutralization epitope which provides the basis for the development of a broadly protecting HPV vaccine. Wide range of protection against different HPV types would eliminate one of the major drawbacks of the commercial, L1 based prophylactic vaccines. Previously, we have reported that insertion of the L2 epitope into a scaffold composed of bacterial thioredoxin protein generates a potent antigen inducing comprehensive protection against different animal and human papillomaviruses...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29212927/mutations-in-the-pa-protein-of-avian-h5n1-influenza-viruses-affect-polymerase-activity-and-mouse-virulence
#20
Gongxun Zhong, Mai Quynh Le, Tiago J S Lopes, Peter Halfmann, Masato Hatta, Shufang Fan, Gabriele Neumann, Yoshihiro Kawaoka
To study the influenza viral determinants of pathogenicity, we characterized two highly pathogenic avian H5N1 influenza viruses isolated in Vietnam in 2012 (A/duck/Vietnam/QT1480/2012; QT1480) and 2013 (A/duck/Vietnam/QT1728/2013; QT1728) and found that the activity of their polymerase complexes differed significantly, even though both viruses were highly pathogenic in mice. Further studies revealed that the PA-S343A/E347D mutations reduced viral polymerase activity and mouse virulence when tested in the genetic background of QT1728 virus...
December 6, 2017: Journal of Virology
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