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    Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism.
    Nature 2017 Feb 20. Epub 2017 Feb 20.
    Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women's Hospital, Boston, Harvard Medical School, Boston, Massachusetts, USA.
    Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8(+) TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). Read More

    Divergent roles of β- and γ-actin isoforms during spread of vaccinia virus.
    Cytoskeleton (Hoboken) 2017 Feb 20. Epub 2017 Feb 20.
    School of Life and Environmental Sciences, The University of Sydney, Sydney, Australia.
    Actin is a major component of the cytoskeleton and is present as two isoforms in non-muscle cells: β- and γ-cytoplasmic actin. These isoforms are strikingly conserved, differing by only four N-terminal amino acids. During spread from infected cells, vaccinia virus (VACV) particles induce localized actin nucleation that propel virus to surrounding cells and facilitate cell-to-cell spread of infection. Read More

    AC dielectrophoretic manipulation and electroporation of vaccinia virus using carbon nanoelectrode arrays.
    Electrophoresis 2017 Feb 17. Epub 2017 Feb 17.
    Department of Chemistry, Kansas State University, Manhattan, KS, 66506.
    This paper reports the capture and detection of vaccinia virus particles based on AC dielectrophoresis (DEP) and electrochemical impedance measurements employing an embedded vertically aligned carbon nanofiber (VACNF) nanoelectrode array (NEA) versus a macroscopic indium-tin-oxide (ITO) transparent electrode in a "points-and-lid" configuration. The nano-DEP device was fabricated by bonding two SU-8 covered electrodes patterned using photolithography. The bottom electrode contains a 200 × 200 μm(2) active region on a randomly distributed NEA and the top electrode contains a microfluidic channel in SU-8 spin-coated on ITO to guide the flow of the virus solution. Read More

    Establishing elements of a synthetic biology platform for Vaccinia virus production: BioBrick™ design, serum-free virus production and microcarrier-based cultivation of CV-1 cells.
    Heliyon 2017 Feb 4;3(2):e00238. Epub 2017 Feb 4.
    Department of Biochemical Engineering, University College London, Bernard Katz Building, London WC1E 6BT, UK.
    Vaccinia virus (VACV) is an established vector for vaccination and is beginning to prove effective as an oncolytic agent. Industrial production of VACV stands to benefit in future from advances made by synthetic biology in genome engineering and standardisation. The CV-1 cell line can be used for VACV propagation and has been used extensively with the CRISPR/Cas9 system for making precise edits of the VACV genome. Read More

    Virus-Specific CD8(+) T Cells Infiltrate Melanoma Lesions and Retain Function Independently of PD-1 Expression.
    J Immunol 2017 Feb 15. Epub 2017 Feb 15.
    Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107;
    It is well known that CD8(+) tumor-infiltrating lymphocytes (TILs) are correlated with positive prognoses in cancer patients and are used to determine the efficacy of immune therapies. Although it is generally assumed that CD8(+) TILs will be tumor-associated Ag (TAA) specific, it is unknown whether CD8(+) T cells with specificity for common pathogens also infiltrate tumors. If so, the presence of these T cells could alter the interpretation of prognostic and diagnostic TIL assays. Read More

    Recombinant Poxvirus and the Tumor Microenvironment: Oncolysis, Immune Regulation and Immunization.
    Biomedicines 2016 12;4(3). Epub 2016 Aug 12.
    Rutgers Cancer Institute of New Jersey, Department of Surgery, Rutgers Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08903-2681, USA.
    Oncolytic viruses (OVs) are being extensively studied for their potential roles in the development of cancer therapy regimens. In addition to their direct lytic effects, OVs can initiate and drive systemic antitumor immunity indirectly via release of tumor antigen, as well as by encoding and delivering immunostimulatory molecules. This combination makes them an effective platform for the development of immunotherapeutic strategies beyond their primary lytic function. Read More

    Identification and characterization of Orf virus 050 protein proteolysis.
    Virus Genes 2017 Feb 11. Epub 2017 Feb 11.
    Department of Laboratory Medicine, The Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, Guangdong, People's Republic of China.
    The Orf virus 050 (ORFV050) gene is located in the core region of the ORFV genome. It is similar to Vaccinia virus (VV) Copenhagen L4R, and encodes the DNA-binding virion core protein VP8, which has structures similar to the VV P25K core protein and may undergo similar proteolytic processing during virus assembly. Three conserved Ala-Gly-X motifs at putative cleavage sites were identified in ORFV050. Read More

    Furanoterpenes, new types of protein tyrosine phosphatase 1B inhibitors, from two Indonesian marine sponges, Ircinia and Spongia spp.
    Bioorg Med Chem Lett 2017 Mar 25;27(5):1159-1161. Epub 2017 Jan 25.
    Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
    Protein tyrosine phosphatase (PTP) 1B negatively regulates the insulin and leptin signaling pathways, and, thus, the clinical application of PTP1B inhibitors to the prevention and treatment of type 2 diabetes and obesity is expected. During our studies on PTP1B inhibitors, two furanosesterterpenes and a C21 furanoterpene were obtained as new types of PTP1B inhibitors from two Indonesian marine sponges. (7E, 12E, 20Z, 18S)-Variabilin (1) and (12E, 20Z, 18S)-8-hydroxyvariabilin (2) from Ircinia sp. Read More

    Dual Detection of Nucleolytic and Proteolytic Markers of Lysosomal Cell Death: DNase II-Type Breaks and Cathepsin D.
    Methods Mol Biol 2017 ;1554:229-236
    Baylor College of Medicine, and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, 77030, USA.
    Lysosomes contain hydrolytic enzymes that can degrade proteins and DNA. Leakage of these reactive compounds through a compromised lysosomal membrane causes lysosomal cell death, which can have apoptotic, necrotic, or mixed morphology. Lysosomal cathepsin proteases, such as cathepsin D, and the lysosomal endonuclease, DNase II, have both been implicated in lysosome-related cell death. Read More

    Proteomic screen for cellular targets of the vaccinia virus F10 protein kinase reveals that phosphorylation of mDia regulates stress fiber formation.
    Mol Cell Proteomics 2017 Feb 9. Epub 2017 Feb 9.
    Medical University of South Carolina, United States;
    Vaccinia virus, a complex dsDNA virus, is unusual in replicating exclusively within the cytoplasm of infected cells. While this prototypic poxvirus encodes >200 proteins utilized during infection, a significant role for host proteins and cellular architecture is increasingly evident. The viral B1 kinase and H1 phosphatase are known to target cellular proteins as well as viral substrates, but little is known about the cellular substrates of the F10 kinase. Read More

    HIV/AIDS vaccine candidates based on replication-competent recombinant poxvirus NYVAC-C-KC expressing trimeric gp140 and Gag-derived VLPs or lacking the viral molecule B19 that inhibits type I interferon activate relevant HIV-1-specific B and T cell immune functions in non-human primates.
    J Virol 2017 Feb 8. Epub 2017 Feb 8.
    Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
    The non-replicating attenuated poxvirus vector NYVAC expressing clade C(CN54) HIV-1 Env(gp120), Gag-Pol-Nef antigens (NYVAC-C) showed in phase I clinical trials limited immunogenicity. To enhance the capacity of the NYVAC vector to trigger broad humoral responses and a more balanced activation of CD4(+) and CD8(+) T cells, here we compared the HIV-1-specific immunogenicity elicited in non-human primates immunized with two replicating NYVAC vectors that have been modified by the insertion of K1L and C7L vaccinia viral host-range genes and express clade C(ZM96) trimeric HIV-1 gp140 protein or a Gag(ZM96)-Pol-Nef(CN54) polyprotein as Gag-derived virus-like particles (termed NYVAC-C-KC). Additionally, one NYVAC-C-KC vector was generated by deleting the viral gene B19R, an inhibitor of type I interferon response (NYVAC-C-KC-ΔB19R). Read More

    The vaccinia virus DNA polymerase and its processivity factor.
    Virus Res 2017 Feb 1. Epub 2017 Feb 1.
    Departments of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, United States; Departments of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, United States; Departments of the Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, United States; Department of Microbiology and Molecular Genetics, Medical College of Wisconsin, Milwaukee, WI 53226, United States. Electronic address:
    Vaccinia virus is the prototypic poxvirus. The 192 kilobase double-stranded DNA viral genome encodes most if not all of the viral replication machinery. The vaccinia virus DNA polymerase is encoded by the E9L gene. Read More

    A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.
    PLoS One 2017 3;12(2):e0171261. Epub 2017 Feb 3.
    Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN, United States of America.
    Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. Read More

    Myxoma Virus dsRNA Binding Protein M029  Inhibits the Type I IFN-Induced Antiviral State in a  Highly Species-Specific Fashion.
    Viruses 2017 Feb 2;9(2). Epub 2017 Feb 2.
    The Biodesign Institute, Center for Immunotherapy, Vaccines, and Virotherapy, Arizona State University, Tempe, AZ 85287-5401, USA.
    Myxoma virus (MYXV) is Leporipoxvirus that possesses a specific rabbit-restricted host tropism but exhibits a much broader  cellular host range in cultured cells. MYXV is able to efficiently  block all aspects of the type I interferon (IFN)-induced  antiviral  state  in rabbit cells, partially in  human  cells  and  very  poorly  in  mouse  cells.  The mechanism(s) of this species-specific inhibition of  type I IFN-induced antiviral state is not well understood. Read More

    Immune Signature of Enhanced Functional Avidity CD8(+) T Cells in vivo Induced by Vaccinia Vectored Vaccine.
    Sci Rep 2017 Feb 3;7:41558. Epub 2017 Feb 3.
    Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
    Functional avidity of T cells is a critical determinant for clearing viral infection and eliminating tumor. Understanding how functional avidity is maintained in T cells is imperative for immunotherapy. However, studies systematically characterize T cell with high functional avidity induced in vivo are still lacking. Read More

    Investigating Viruses During the Transformation of Molecular Biology.
    J Biol Chem 2017 Jan 30. Epub 2017 Jan 30.
    National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
    This Reflections article describes my early work on viral enzymes and the discovery of mRNA capping, how my training in medicine and biochemistry merged as I evolved into a virologist, the development of viruses as vaccine vectors, and how scientific and technological developments during the 1970's and beyond set the stage for the interrogation of nearly every step in the reproductive cycle of vaccinia virus (VACV), a large DNA virus with about 200 genes. The reader may view this article as a work in progress, since I remain actively engaged in research at the NIH notwithstanding 50 memorable years there. Read More

    Viral Vector Malaria Vaccines Induce High-Level T Cell and Antibody Responses in West African Children and Infants.
    Mol Ther 2017 Feb;25(2):547-559
    The Jenner Institute Laboratories, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK. Electronic address:
    Heterologous prime-boosting with viral vectors encoding the pre-erythrocytic antigen thrombospondin-related adhesion protein fused to a multiple epitope string (ME-TRAP) induces CD8(+) T cell-mediated immunity to malaria sporozoite challenge in European malaria-naive and Kenyan semi-immune adults. This approach has yet to be evaluated in children and infants. We assessed this vaccine strategy among 138 Gambian and Burkinabe children in four cohorts: 2- to 6-year olds in The Gambia, 5- to 17-month-olds in Burkina Faso, and 5- to 12-month-olds and 10-week-olds in The Gambia. Read More

    HIV-1 Conserved Mosaics Delivered by Regimens with Integration-Deficient DC-Targeting Lentiviral Vector Induce Robust T Cells.
    Mol Ther 2017 Feb;25(2):494-503
    The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK; International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-8555, Japan. Electronic address:
    To be effective against HIV type 1 (HIV-1), vaccine-induced T cells must selectively target epitopes, which are functionally conserved (present in the majority of currently circulating and reactivated HIV-1 strains) and, at the same time, beneficial (responses to which are associated with better clinical status and control of HIV-1 replication), and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising vaccine strategies; nevertheless, induction of robust long-term memory remains challenging. To this end, lentiviral vectors induce high frequencies of memory cells due to their low-inflammatory nature, while typically inducing only low anti-vector immune responses. Read More

    Entirely plasmid-based reverse genetics system for rotaviruses.
    Proc Natl Acad Sci U S A 2017 Jan 30. Epub 2017 Jan 30.
    Laboratory of Viral Replication, International Research Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871 Japan;
    Rotaviruses (RVs) are highly important pathogens that cause severe diarrhea among infants and young children worldwide. The understanding of the molecular mechanisms underlying RV replication and pathogenesis has been hampered by the lack of an entirely plasmid-based reverse genetics system. In this study, we describe the recovery of recombinant RVs entirely from cloned cDNAs. Read More

    Online Size-exclusion and Ion-exchange Chromatography on a SAXS Beamline.
    J Vis Exp 2017 Jan 5(119). Epub 2017 Jan 5.
    Groupe de Microscopie Electronique et Méthodes, Institut de Biologie Structurale;
    Biological small angle X-ray scattering (BioSAXS) is a powerful technique in molecular and structural biology used to determine solution structure, particle size and shape, and surface-to-volume ratio of macromolecules. The technique is applicable to a very wide variety of solution conditions spanning a broad range of concentrations, pH values, ionic strengths, temperatures, additives, etc., but the sample is required to be monodisperse. Read More

    Detection of Vaccinia Virus in Urban Domestic Cats, Brazil.
    Emerg Infect Dis 2017 Feb;23(2):360-362
    We investigated possible vaccinia virus (VACV) in urban house cats in Brazil. Serum samples from 6 cats were positive for VACV by PCR, indicating likely VACV circulation among house cats in urban areas of Brazil. This finding highlights the importance of epidemiologic surveillance to avoid outbreaks among urban human populations. Read More

    Immunogenicity of modified vaccinia virus Ankara expressing the hemagglutinin stalk domain of pandemic (H1N1) 2009 influenza virus.
    Pathog Glob Health 2017 Jan 12:1-7. Epub 2017 Jan 12.
    a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
    Background: Vaccination offers protection against influenza, although current vaccines need to be reformulated each year. The development of a broadly protective influenza vaccine would guarantee the induction of heterosubtypic immunity also against emerging influenza viruses of a novel subtype. Vaccine candidates based on the stalk region of the hemagglutinin (HA) have the potential to induce broad and persistent protection against diverse influenza A viruses. Read More

    Cutaneous Deficiency of Filaggrin and STAT3 Exacerbates Vaccinia Disease In Vivo.
    PLoS One 2017 12;12(1):e0170070. Epub 2017 Jan 12.
    Food and Drug Administration, Center for Biologics Evaluation and Research, 10903 New Hampshire Ave., Silver Spring, MD, United States of America.
    Rationale: Defects in filaggrin and STAT3 are associated with atopic dermatitis (AD) and susceptibility to severe skin infection.

    Methods: We evaluated skin infection with the current smallpox vaccine, ACAM-2000, in immunosuppressed mice with combined cutaneous deficiency in filaggrin and STAT3. In parallel, early events post-infection with ACAM-2000 were investigated in cultured keratinocytes in which filaggrin expression was knocked down via siRNA. Read More

    Protective immunity against influenza in HLA-A2 transgenic mice by modified vaccinia virus Ankara vectored vaccines containing internal influenza proteins.
    Pathog Glob Health 2017 Jan 12:1-7. Epub 2017 Jan 12.
    a Department of Infectious Diseases , Istituto Superiore di Sanità , Rome , Italy.
    Background: The emergence of novel strains of influenza A viruses with hemagglutinins (HAs) that are antigenically distinct from those circulating in humans, and thus have pandemic potential, pose concerns and call for the development of more broadly protective influenza vaccines. In the present study, modified vaccinia virus Ankara (MVA) encoding internal influenza antigens were evaluated for their immunogenicity and ability to protect HLA-A2.1 transgenic (AAD) mice from infection with influenza viruses. Read More

    Coherent Brightfield Microscopy Provides the Spatiotemporal Resolution To Study Early Stage Viral Infection in Live Cells.
    ACS Nano 2017 Jan 13. Epub 2017 Jan 13.
    Institute of Atomic and Molecular Sciences, Academia Sinica , Taipei 10617, Taiwan.
    Viral infection starts with a virus particle landing on a cell surface followed by penetration of the plasma membrane. Due to the difficulty of measuring the rapid motion of small-sized virus particles on the membrane, little is known about how a virus particle reaches an endocytic site after landing at a random location. Here, we use coherent brightfield (COBRI) microscopy to investigate early stage viral infection with ultrahigh spatiotemporal resolution. Read More

    Induction and Analysis of Bronchus-Associated Lymphoid Tissue.
    Methods Mol Biol 2017 ;1559:185-198
    Institute of Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
    Bronchus-associated lymphoid tissue (BALT) forms spontaneously in the lung after pulmonary infection and has been identified as a highly organized lymphoid structure supporting the efficient priming of T cells in the lung. To explore the mechanisms and instructive signals controlling BALT neogenesis we used both, a single dose of vaccinia virus MVA and repeated inhalations of heat-inactivated Pseudomonas aeruginosa (P. aeruginosa). Read More

    Preparation of Cell Cultures and Vaccinia Virus Stocks.
    Curr Protoc Mol Biol 2017 Jan 5;117:16.16.1-16.16.18. Epub 2017 Jan 5.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
    The culturing of cell lines used with vaccinia virus, both as monolayer and in suspension, is described. The preparation of chick embryo fibroblasts (CEF) is presented for use in the production of the highly attenuated and host range-restricted modified vaccinia virus Ankara (MVA) strain of vaccinia virus. Protocols for the preparation, titration, and trypsinization of vaccinia virus stocks, as well as viral DNA preparation and virus purification methods are also included. Read More

    Generation of Recombinant Vaccinia Viruses.
    Curr Protoc Mol Biol 2017 Jan 5;117:16.17.1-16.17.18. Epub 2017 Jan 5.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
    This unit describes how to infect cells with vaccinia virus and then transfect them with a plasmid-transfer vector or PCR fragment to generate a recombinant virus. Selection and screening methods used to isolate recombinant viruses and a method for the amplification of recombinant viruses are described. Finally, a method for live immunostaining that has been used primarily for detection of recombinant modified vaccinia virus Ankara (MVA) is presented. Read More

    Induction of necroptotic cell death by viral activation of the RIG-I or STING pathway.
    Cell Death Differ 2017 Jan 6. Epub 2017 Jan 6.
    Department of Molecular and Cell Biology and Cancer Research Laboratory, 469 LSA, University of California, Berkeley, CA 94720-3200, USA.
    Necroptosis is a form of necrotic cell death that requires the activity of the death domain-containing kinase RIP1 and its family member RIP3. Necroptosis occurs when RIP1 is deubiquitinated to form a complex with RIP3 in cells deficient in the death receptor adapter molecule FADD or caspase-8. Necroptosis may play a role in host defense during viral infection as viruses like vaccinia can induce necroptosis while murine cytomegalovirus encodes a viral inhibitor of necroptosis. Read More

    Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.
    Adv Virus Res 2017 1;97:187-243. Epub 2016 Aug 1.
    German Center for Infection Research (DZIF), Institute for Infectious Diseases and Zoonoses, LMU University of Munich, Munich, Germany. Electronic address:
    Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. Read More

    Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.
    PLoS One 2017 3;12(1):e0169247. Epub 2017 Jan 3.
    Tripler Army Medical Center, Honolulu, Hawaii, United States of America.
    Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years) and protective. Read More

    Reprogramming antitumor immunity against chemoresistant ovarian cancer by a CXCR4 antagonist-armed viral oncotherapy.
    Mol Ther Oncolytics 2016 14;3:16034. Epub 2016 Dec 14.
    Department of Immunology, Roswell Park Cancer Institute , Buffalo, New York, USA.
    Ovarian cancer remains the most lethal gynecologic malignancy owing to late detection, intrinsic and acquired chemoresistance, and remarkable heterogeneity. Here, we explored approaches to inhibit metastatic growth of murine and human ovarian tumor variants resistant to paclitaxel and carboplatin by oncolytic vaccinia virus expressing a CXCR4 antagonist to target the CXCL12 chemokine/CXCR4 receptor signaling axis alone or in combination with doxorubicin. The resistant variants exhibited augmented expression of the hyaluronan receptor CD44 and CXCR4 along with elevated Akt and ERK1/2 activation and displayed an increased susceptibility to viral infection compared with the parental counterparts. Read More

    Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine.
    Infect Immun 2017 Mar 23;85(3). Epub 2017 Feb 23.
    The Jenner Institute, University of Oxford, Oxford, United Kingdom.
    Efforts are under way to improve the efficacy of subunit malaria vaccines through assessments of new adjuvants, vaccination platforms, and antigens. In this study, we further assessed the Plasmodium falciparum antigen upregulated in infective sporozoites 3 (PfUIS3) as a vaccine candidate. PfUIS3 was expressed in the viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) and used to immunize mice in a prime-boost regimen. Read More

    Vector-based genetically modified vaccines: Exploiting Jenner's legacy.
    Vaccine 2016 Oct 28. Epub 2016 Oct 28.
    Vrije Universiteit Amsterdam, Earth & Life Sciences, Athena Institute, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands. Electronic address:
    The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of 'smarter' vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. Read More

    Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.
    AIDS Res Hum Retroviruses 2017 Jan 27. Epub 2017 Jan 27.
    2 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm, Sweden .
    We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). Read More

    Viral vector vaccines protect cockatiels from inflammatory lesions after heterologous parrot bornavirus 2 challenge infection.
    Vaccine 2017 Jan 22;35(4):557-563. Epub 2016 Dec 22.
    Institute for Virology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hermann-Herder-Str. 11, D-79104 Freiburg, Germany. Electronic address:
    Avian bornaviruses are causative agents of proventricular dilatation disease (PDD), a chronic neurologic and often fatal disorder of psittacines including endangered species. To date no causative therapy or immunoprophylaxis is available. Our previous work has shown that viral vector vaccines can delay the course of homologous bornavirus challenge infections but failed to protect against PDD when persistent infection was not prevented. Read More

    Sequential administration of a MVA-based MUC1 cancer vaccine and the TLR9 ligand Litenimod (Li28) improves local immune defense against tumors.
    Vaccine 2017 Jan 21;35(4):577-585. Epub 2016 Dec 21.
    TRANSGENE S.A., 400 Boulevard Gonthier d'Andernach, Parc d'Innovation, 67405 Illkirch-Graffenstaden, France. Electronic address:
    TG4010 is an immunotherapeutic vaccine based on Modified Vaccinia virus Ankara (MVA) encoding the human tumor-associated antigen MUC1 and human IL-2. In combination with first-line standard of care chemotherapy in advanced metastatic non-small-cell lung cancer (NSCLC), repeated subcutaneous injection of TG4010 improved progression-free survival in phase 2b clinical trials. In preclinical tumor models, MVATG9931, the research version of TG4010, conferred antigen-specific responses against the weak antigen human MUC1. Read More

    Sublingual immunization with Japanese encephalitis virus vaccine effectively induces immunity through both cellular and humoral immune responses in mice.
    Microbiol Immunol 2016 Dec;60(12):846-853
    Department of Biotechnology, Catholic University of Korea, Bucheon, 420-743.
    The Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis. Although there are four classes of vaccines against JEV, all of them are administered by s.c or i. Read More

    Ribosome Profiling Reveals Translational Upregulation of Cellular Oxidative Phosphorylation mRNAs during Vaccinia Virus-Induced Host Shutoff.
    J Virol 2017 Mar 14;91(5). Epub 2017 Feb 14.
    Division of Biology, Kansas State University, Manhattan, Kansas, USA
    Vaccinia virus infection causes a host shutoff that is marked by global inhibition of host protein synthesis. Though the host shutoff may facilitate reallocation of cellular resources for viral replication and evasion of host antiviral immune responses, it poses a challenge for continuous synthesis of cellular proteins that are important for viral replication. It is, however, unclear whether and how certain cellular proteins may be selectively synthesized during the vaccinia virus-induced host shutoff. Read More

    Chronic Type I IFN Is Sufficient To Promote Immunosuppression through Accumulation of Myeloid-Derived Suppressor Cells.
    J Immunol 2017 Feb 21;198(3):1156-1163. Epub 2016 Dec 21.
    INSERM, U1016, Institut Cochin, 75014 Paris, France;
    Failure of the immune system to eradicate viruses results in chronic viral infections, which are associated with increased susceptibility to secondary infections. Pathogenic HIV or lymphocytic choriomeningitis virus chronic infections display a persistent type I IFN signature. In chronic lymphocytic choriomeningitis virus infection, blockade of type I IFN signaling partially restores antiviral responses. Read More

    Concomitant helminth infection downmodulates the Vaccinia virus-specific immune response and potentiates virus-associated pathology.
    Int J Parasitol 2017 Jan 18;47(1):1-10. Epub 2016 Dec 18.
    Department of Parasitology, Biological Sciences Institute, Universidade Federal de Minas Gerais, Brazil. Electronic address:
    The aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. Severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice, compared with VACV mono-infected mice. Immunopathological analysis suggested that the ablation of CD8(+) T cells, the marked reduction of circulating CD4(+) T cells producing IFN-γ, and the robust pulmonary inflammation were associated with the increase of morbidity/mortality in co-infection and subsequently with the negative impact of concomitant pulmonary ascariasis and respiratory VACV infection for the host. Read More

    A bioinformatics pipeline to search functional motifs within whole-proteome data: a case study of poxviruses.
    Virus Genes 2016 Dec 20. Epub 2016 Dec 20.
    Department of Molecular Biology, Umeå University, 901 87, Umeå, Sweden.
    Proteins harbor domains or short linear motifs, which facilitate their functions and interactions. Finding functional motifs in protein sequences could predict the putative cellular roles or characteristics of hypothetical proteins. In this study, we present Shetti-Motif, which is an interactive tool to (i) map UniProt and PROSITE flat files, (ii) search for multiple pre-defined consensus patterns or experimentally validated functional motifs in large datasets protein sequences (proteome-wide), (iii) search for motifs containing repeated residues (low-complexity regions, e. Read More

    The EB66® cell line as a valuable cell substrate for MVA-based vaccines production.
    Vaccine 2016 Nov 27;34(48):5878-5885. Epub 2016 Oct 27.
    Valneva SE, 6 rue Alain Bombard, 44800 Saint-Herblain, France.
    The selection of a cell substrate is a critical step for the development and manufacturing of a viral vaccine candidate. Several parameters such as cell susceptibility and permissiveness to the viral pathogens but also performance in terms of viral antigens quality and production yields are important considerations when identifying the ideal match between a viral vaccine and cell substrate. The modified vaccinia virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform, however only limited cell substrates have been tested or are available for industrialization. Read More

    Colonization of xenograft tumors by oncolytic vaccinia virus (VACV) results in enhanced tumor killing due to the involvement of myeloid cells.
    J Transl Med 2016 Dec 20;14(1):340. Epub 2016 Dec 20.
    Department of Biochemistry, Biocenter, University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
    Background: The mechanisms by which vaccinia virus (VACV) interacts with the innate immune components are complex and involve different mechanisms. iNOS-mediated NO production by myeloid cells is one of the central antiviral mechanisms and this study aims to investigate specifically whether iNOS-mediated NO production by myeloid cells, is involved in tumor eradication following the virus treatment.

    Methods: Human colon adenocarcinoma (HCT-116) xenograft tumors were infected by VACV. Read More

    A novel anti-viral role for STAT3 in IFN-α signalling responses.
    Cell Mol Life Sci 2016 Dec 17. Epub 2016 Dec 17.
    School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute (TBSI), Trinity College Dublin, Dublin, Ireland.
    The cytokine, Interferon (IFN)-α, induces a wide spectrum of anti-viral mediators, via the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. STAT1 and STAT2 are well characterised to upregulate IFN-stimulated gene (ISG) expression; but even though STAT3 is also activated by IFN-α, its role in anti-viral ISG induction is unclear. Several viruses, including Hepatitis C and Mumps, reduce cellular STAT3 protein levels, via the promotion of ubiquitin-mediated proteasomal degradation. Read More

    Safety, Immunogenicity and Efficacy of Prime-Boost Vaccination with ChAd63 and MVA Encoding ME-TRAP against Plasmodium falciparum Infection in Adults in Senegal.
    PLoS One 2016 15;11(12):e0167951. Epub 2016 Dec 15.
    Parasitology department, Faculty of Medicine University Cheikh Anta Diop, Dakar, Senegal.
    Malaria transmission is in decline in some parts of Africa, partly due to the scaling up of control measures. If the goal of elimination is to be achieved, additional control measures including an effective and durable vaccine will be required. Studies utilising the prime-boost approach to deliver viral vectors encoding the pre-erythrocytic antigen ME-TRAP (multiple epitope thrombospondin-related adhesion protein) have shown promising safety, immunogenicity and efficacy in sporozoite challenge studies. Read More

    Vaccinia Virus Immunomodulator A46: A Lipid and Protein-Binding Scaffold for Sequestering Host TIR-Domain Proteins.
    PLoS Pathog 2016 Dec 14;12(12):e1006079. Epub 2016 Dec 14.
    Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter, Dr. Bohr-Gasse 9/3, Vienna, Austria.
    Vaccinia virus interferes with early events of the activation pathway of the transcriptional factor NF-kB by binding to numerous host TIR-domain containing adaptor proteins. We have previously determined the X-ray structure of the A46 C-terminal domain; however, the structure and function of the A46 N-terminal domain and its relationship to the C-terminal domain have remained unclear. Here, we biophysically characterize residues 1-83 of the N-terminal domain of A46 and present the X-ray structure at 1. Read More

    Serro 2 Virus Highlights the Fundamental Genomic and Biological Features of a Natural Vaccinia Virus Infecting Humans.
    Viruses 2016 Dec 10;8(12). Epub 2016 Dec 10.
    Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention (CCID/CDC), Atlanta, 30329-4027 GA, USA.
    Vaccinia virus (VACV) has been implicated in infections of dairy cattle and humans, and outbreaks have substantially impacted local economies and public health in Brazil. During a 2005 outbreak, a VACV strain designated Serro 2 virus (S2V) was collected from a 30-year old male milker. Our aim was to phenotypically and genetically characterize this VACV Brazilian isolate. Read More

    Dual-specific chimeric antigen receptor T cells and an indirect vaccine eradicate a variety of large solid tumors in an immunocompetent, self-antigen setting.
    Clin Cancer Res 2016 Dec 13. Epub 2016 Dec 13.
    Cancer Immunology Program, Peter MacCallum Cancer Center
    Purpose: While adoptive transfer of T cells bearing a chimeric antigen receptor (CAR) can eliminate substantial burdens of some leukemias, the ultimate challenge remains the eradication of large solid tumors for most cancers. We aimed to develop an immunotherapy approach effective against large tumors in an immunocompetent, self-antigen preclinical mouse model.

    Experimental Design: In this study, we generated dual-specific T cells expressing both a CAR specific for Her2 and a TCR specific for the melanocyte protein (gp100). Read More

    Heterologous boosting with recombinant VSV-846 in BCG-primed mice confers improved protection against Mycobacterium infection.
    Hum Vaccin Immunother 2016 Dec 14. Epub 2016 Dec 14.
    a Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University , Suzhou , 215123 , P R China.
    Tuberculosis (TB) remains a major health problem worldwide, and the development of effective vaccines is urgently needed. Vaccination strategies based on heterologous prime-boost protocols using Mycobacterium bovis bacillus Calmette-Guérin (BCG) as primer and modified vaccinia virus Ankara strain expressing the mycobacterial antigen Ag85A (MVA85A) as booster may increase the protective efficacy of BCG. In addition, vaccination with the recombinant viral vaccine vesicular stomatitis virus (VSV)-846 (Rv3615c, Mtb10. Read More

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