15,667 results match your criteria Vaccinia


Molecular and Cellular Dynamics in the Skin, the Lymph Nodes, and the Blood of the Immune Response to Intradermal Injection of Modified Vaccinia Ankara Vaccine.

Front Immunol 2018 25;9:870. Epub 2018 Apr 25.

Immunology of Viral Infections and Autoimmune Diseases, IDMIT Department, CEA - Université Paris Sud 11 - INSERM U1184, Fontenay-aux-Roses, France.

New vaccine design approaches would be greatly facilitated by a better understanding of the early systemic changes, and those that occur at the site of injection, responsible for the installation of a durable and oriented protective response. We performed a detailed characterization of very early infection and host response events following the intradermal administration of the modified vaccinia virus Ankara as a live attenuated vaccine model in non-human primates. Integrated analysis of the data obtained from imaging, histology, flow cytometry, multiplex cytokine, and transcriptomic analysis using tools derived from systems biology, such as co-expression networks, showed a strong early local and systemic inflammatory response that peaked at 24 h, which was then progressively replaced by an adaptive response during the installation of the host response to the vaccine. Read More

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April 2018
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Septins suppress the release of vaccinia virus from infected cells.

J Cell Biol 2018 Jun 19. Epub 2018 Jun 19.

Cellular Signalling and Cytoskeletal Function Laboratory, The Francis Crick Institute, London, England, UK

Septins are conserved components of the cytoskeleton that play important roles in many fundamental cellular processes including division, migration, and membrane trafficking. Septins can also inhibit bacterial infection by forming cage-like structures around pathogens such as We found that septins are recruited to vaccinia virus immediately after its fusion with the plasma membrane during viral egress. RNA interference-mediated depletion of septins increases virus release and cell-to-cell spread, as well as actin tail formation. Read More

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June 2018
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Structure of a lipid-bound viral membrane assembly protein reveals a modality for enclosing the lipid bilayer.

Proc Natl Acad Sci U S A 2018 Jun 18. Epub 2018 Jun 18.

Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, OK 74078;

Cellular membranes are maintained as closed compartments, broken up only transiently during membrane reorganization or lipid transportation. However, open-ended membranes, likely derived from scissions of the endoplasmic reticulum, persist in vaccinia virus-infected cells during the assembly of the viral envelope. A group of viral membrane assembly proteins (VMAPs) were identified as essential for this process. Read More

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Induction of Cross-Clade Antibody and T-Cell Responses by an MVA-Based Influenza H5N1 Vaccine in a Randomized Phase I/IIa Clinical Trial.

J Infect Dis 2018 Apr 18. Epub 2018 Apr 18.

Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, Rotterdam, The Netherlands.

Background: Highly pathogenic avian influenza viruses continue to circulate in poultry and wild birds and occasionally infect humans, sometimes with fatal outcome. Development of vaccines is a priority to prepare for potential pandemics, however complicated by antigenic variation of the surface glycoprotein hemagglutinin. We report the immunological profile induced by human immunization with Modified Vaccinia virus Ankara expressing the hemagglutinin gene of H5N1 virus A/Vietnam/1194/04 (rMVA-H5). Read More

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Oncolytic Viruses for Multiple Myeloma Therapy.

Cancers (Basel) 2018 Jun 14;10(6). Epub 2018 Jun 14.

Division of Translational and Regenerative Medicine, Department of Medicine and The University of Arizona Cancer Center, Tucson, AZ 85724, USA.

Although recent treatment advances have improved outcomes for patients with multiple myeloma (MM), the disease frequently becomes refractory to current therapies. MM thus remains incurable for most patients and new therapies are urgently needed. Oncolytic viruses are a promising new class of therapeutics that provide tumor-targeted therapy by specifically infecting and replicating within cancerous cells. Read More

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Exploring the role of oncolytic viruses in hepatobiliary cancers.

Immunotherapy 2018 06 14. Epub 2018 Jun 14.

Assistant Professor of Medicine, Department of Medicine, Hematology & Oncology division, University of Arizona, Tucson, AZ 85721, USA.

The standard of care for early hepatobiliary cancers (HBC) includes surgical resection. Liver transplantations or locoregional therapies are beneficial in early hepatocellular carcinoma (HCC) under certain circumstances. Systemic treatments have some benefit in advanced HBC, though long-term prognosis remains poor. Read More

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Targeting Poxvirus Decapping Enzymes and mRNA Decay to Generate an Effective Oncolytic Virus.

Mol Ther Oncolytics 2018 Mar 31;8:71-81. Epub 2018 Jan 31.

Department of Microbiology, NYU School of Medicine, New York, NY, USA.

Through the action of two virus-encoded decapping enzymes (D9 and D10) that remove protective caps from mRNA 5'-termini, Vaccinia virus (VACV) accelerates mRNA decay and limits activation of host defenses. D9- or D10-deficient VACV are markedly attenuated in mice and fail to counter cellular double-stranded RNA-responsive innate immune effectors, including PKR. Here, we capitalize upon this phenotype and demonstrate that VACV deficient in either decapping enzyme are effective oncolytic viruses. Read More

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Protection by universal influenza vaccine is mediated by memory CD4 T cells.

Vaccine 2018 07 7;36(29):4198-4206. Epub 2018 Jun 7.

Center of Influenza Research, School of Public Health, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

There is a diverse array of influenza viruses which circulate between different species, reassort and drift over time. Current seasonal influenza vaccines are ineffective in controlling these viruses. We have developed a novel universal vaccine which elicits robust T cell responses and protection against diverse influenza viruses in mouse and human models. Read More

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July 2018
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Lectin Enhances Oncolytic Vaccinia Virus Replication to Suppress In Vivo Hepatocellular Carcinoma Growth.

Mar Drugs 2018 Jun 7;16(6). Epub 2018 Jun 7.

College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Lectins play diverse roles in physiological processes as biological recognition molecules. In this report, a gene encoding Lectin (TTL) was inserted into an oncolytic vaccinia virus (oncoVV) vector to form oncoVV-TTL, which showed significant antitumor activity in a hepatocellular carcinoma mouse model. Furthermore, TTL enhanced oncoVV replication through suppressing antiviral factors expression such as interferon-inducible protein 16 (IFI16), mitochondrial antiviral signaling protein (MAVS) and interferon-beta (IFN-β). Read More

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CD8 T CELL RESPONSES TO AN IMMUNODOMINANT EPITOPE WITHIN THE NON-STRUCTURAL PROTEIN NS1 PROVIDES WIDE IMMUNOPROTECTION AGAINST BLUETONGUE VIRUS IN IFNAR(-/-) MICE.

J Virol 2018 Jun 6. Epub 2018 Jun 6.

Center for Animal Health Research, INIA-CISA, 28130 Valdeolmos, Madrid, Spain.

The development of vaccines against Bluetongue, a prevalent livestock disease, has been focused on surface antigens that induce strong neutralizing antibody responses. Because their antigenic variability, these vaccines are usually serotype restricted. We now show that a single highly conserved non-structural protein, NS1, expressed in a modified vaccinia Ankara virus (MVA) vector can provide multiserotype protection in IFNAR(-/-) 129 mice against Bluetongue virus that is largely dependent on CD8 T cell responses. Read More

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Batf3 Dependent Dendritic Cells Promote Optimal CD8 T Cell Responses Against Respiratory Poxvirus Infection.

J Virol 2018 Jun 6. Epub 2018 Jun 6.

Department of Pathology, Immunology & Laboratory Medicine, University of Florida, Gainesville, FL, USA.

Respiratory infection with vaccinia virus (VacV) elicits robust CD8 T cell responses that play an important role in host resistance. In the lung, VacV encounters multiple tissue resident APC populations, but which cell plays a dominant role in priming of virus-specific CD8 effector T cell responses remains poorly defined. We used Batf3 mice to investigate the impact of CD103 DC and CD8α DC deficiency on anti-VacV CD8 T cell responses. Read More

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Immunogenicity of propagation-restricted vesicular stomatitis virus encoding Ebola virus glycoprotein in guinea pigs.

J Gen Virol 2018 Jun 5. Epub 2018 Jun 5.

1​Institut für Virologie und Immunologie (IVI), Sensemattstrasse 293, CH-3147 Mittelhäusern, Switzerland.

Vesicular stomatitis virus (VSV) expressing the Ebola virus (EBOV) glycoprotein (GP) in place of the VSV glycoprotein G (VSV/EBOV-GP) is a promising EBOV vaccine candidate which has already entered clinical phase 3 studies. Although this chimeric virus was tolerated overall by volunteers, it still caused viremia and adverse effects such as fever and arthritis, suggesting that it might not be sufficiently attenuated. In this study, the VSV/EBOV-GP vector was further modified in order to achieve attenuation while maintaining immunogenicity. Read More

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June 2018
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DNA Vaccine-Induced Long-Lasting Cytotoxic T Cells Targeting Conserved Elements of Human Immunodeficiency Virus Gag Are Boosted Upon DNA or Recombinant Modified Vaccinia Ankara Vaccination.

Hum Gene Ther 2018 Jun 21. Epub 2018 Jun 21.

1 Human Retrovirus Pathogenesis Section, National Cancer Institute, Frederick, Maryland.

DNA-based vaccines able to induce efficient cytotoxic T-cell responses targeting conserved elements (CE) of human immunodeficiency virus type 1 (HIV-1) Gag have been developed. These CE were selected by stringent conservation, the ability to induce T-cell responses with broad human leukocyte antigen coverage, and the association between recognition of CE epitopes and viral control in HIV-infected individuals. Based on homology to HIV, a simian immunodeficiency virus p27 CE DNA vaccine has also been developed. Read More

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June 2018
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p53 and the Viral Connection: Back into the Future .

Cancers (Basel) 2018 Jun 4;10(6). Epub 2018 Jun 4.

Department of Molecular Cell Biology, Weizmann Institute of Science, 76100 Rehovot, Israel.

The discovery of the tumor suppressor p53, through its interactions with proteins of tumor-promoting viruses, paved the way to the understanding of p53 roles in tumor virology. Over the years, accumulating data suggest that WTp53 is involved in the viral life cycle of non-tumor-promoting viruses as well. These include the influenza virus, smallpox and vaccinia viruses, the Zika virus, West Nile virus, Japanese encephalitis virus, Human Immunodeficiency Virus Type 1, Human herpes simplex virus-1, and more. Read More

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Performance of Homologous and Heterologous Prime-Boost Immunization Regimens of Recombinant Adenovirus and Modified Vaccinia Virus Ankara Expressing an Ag85B-TB10.4 Fusion Protein against Mycobacterium tuberculosis.

J Microbiol Biotechnol 2018 Apr 23. Epub 2018 Apr 23.

National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University, Changchun 130012, P.R. China.

Tuberculosis (TB) remains a serious health issue around the word. Adenovirus (Ad)-based vaccine and modified vaccinia virus Ankara (MVA)-based vaccine have emerged as two of the most promising immunization candidates over the past few years. However, the performance of the homologous and heterologous prime-boost immunization regimens of these two viral vector-based vaccines remains unclear. Read More

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Interleukin-32 promotes detachment and activation of human Langerhans cells in a human skin explant model.

Br J Dermatol 2018 May 28. Epub 2018 May 28.

Sorbonne Universités UPMC Université Paris 06, UMRS CR7, Inserm U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses-Paris (Cimi-Paris), 91 Boulevard de l'Hôpital, 75013, Paris, France.

Background: Cross-talk between skin keratinocytes (KCs) and Langerhans cells (LCs) plays a fundamental role in the body's first line of immunological defences. However, the mechanism behind the interaction between these two major epidermal cells is unknown. Interleukin (IL)-32 is produced in inflammatory skin disorders. Read More

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May 2018
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Complete Genome Sequence of Buffalopox Virus.

Genome Announc 2018 May 24;6(21). Epub 2018 May 24.

National Infection Service Research, Public Health England, Porton Down, United Kingdom.

The first complete genome assembly of buffalopox virus isolate Karachi 2005, with a length of 195,630 bp, is presented here. Phylogenetic analysis shows the virus to cluster within species, and the genome contains 177 protein-coding sequences. Read More

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Vaccinia Virus Protein C6: A Multifunctional Interferon Antagonist.

Authors:
Geoffrey L Smith

Adv Exp Med Biol 2018 ;1052:1-7

Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK.

Vaccinia virus (VACV) is the prototypic member of the Orthopoxvirus genus of the Poxviridae. It is also the live vaccine that was used to eradicate smallpox. Like other poxviruses, VACV replicates in the cytoplasm and has a large double-stranded (ds)DNA genome and a complex virion. Read More

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January 2018

Vaccinia-based vaccines to biothreat and emerging viruses.

Biotechnol Genet Eng Rev 2018 Apr 21;34(1):107-121. Epub 2018 May 21.

b Medical Microbiology and Immunology , University of Alberta , Edmonton , Canada.

The past few years have seen a rash of emerging viral diseases, including the Ebola crisis in West Africa, the pandemic spread of chikungunya, and the recent explosion of Zika in South America. Vaccination is the most reliable and cost-effective method of control of infectious diseases, however, there is often a long delay in production and approval in getting new vaccines to market. Vaccinia was the first vaccine developed for the successful eradication of smallpox and has properties that make it attractive as a universal vaccine vector. Read More

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The immune response of rhesus macaques to novel vaccines comprising hepatitis B virus S, PreS1, and Core antigens.

Vaccine 2018 06 16;36(26):3740-3746. Epub 2018 May 16.

MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, People's Republic of China. Electronic address:

Therapeutic vaccines represent a unique approach to hepatitis B virus (HBV) treatment and have the potential to induce long-term control of infection. This study explored the immune responses of rhesus macaques to novel vaccines comprising the S, PreS1, and Core antigens of the HBV that showed promise as prophylactic and therapeutic approaches in a mouse model. The tested vaccines included two DNA vaccines (pVRC-SS1, pVRC-CS1), an HBV particle subunit (HBSS1) vaccine and the recombinant vaccinia virus- (RVJ-) based vaccines (RVJSS1 and RVJCS1) in which SS1 containing S (1-223 aa) and PreS1 (21-47 aa), CS1 containing Core (1-144 aa) and PreS1 (1-42 aa). Read More

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Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis.

Clin Cancer Res 2018 May 17. Epub 2018 May 17.

Internal Medicine I, Medical University Hospital.

Objective: Peritoneal carcinomatosis (PC) is common in advanced tumor stages or disease recurrence arising from gastrointestinal cancers, gynecologic malignancies, or primary peritoneal carcinoma. Since current therapies are mostly ineffective, new thera-peutic approaches are needed. Here, we report on a phase I study designed to assess safety, MTD, and anti-tumor activity of intra-peri-toneal (i. Read More

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Efficient delivery of HCMV T cell antigens by attenuated Sendai virus vectors.

J Virol 2018 May 16. Epub 2018 May 16.

Institute of Medical Microbiology and Hygiene, Universität Regensburg, Franz-Josef- Strauß-Allee 11, 93053 Regensburg, Germany

Human Cytomegalovirus (HCMV) represents a major cause of clinical complications during pregnancy as well as immunosuppression and the licensing of a protective HCMV vaccine remains an unmet global need. Herein, we designed and validated novel Sendai virus (SeV) vectors delivering T cell immunogens IE-1 and pp65. To enhance vector safety, we used a replication-deficient strain (rdSeV) that infects target cells in a non-productive manner while retaining viral gene expression. Read More

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The emerging role of oncolytic virus therapy against cancer.

Chin Clin Oncol 2018 Apr;7(2):16

Mayo Clinic, Rochester, MN, USA.

This review discusses current clinical advancements in oncolytic viral therapy, with a focus on the viral platforms approved for clinical use and highlights the benefits each platform provides. Three oncolytic viruses (OVs), an echovirus, an adenovirus, and a herpes simplex-1 virus, have passed governmental regulatory approval in Latvia, China, and the USA and EU. Numerous other recombinant viruses from diverse families are in clinical testing in cancer patients and we highlight the design features of selected examples, including adenovirus, herpes simplex virus, measles virus, retrovirus, reovirus, vaccinia virus, vesicular stomatitis virus. Read More

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Distribution and absence of generalized lesions in mice following single dose intramuscular inoculation of the vaccine candidate MVA-MERS-S.

Biologicals 2018 May 11. Epub 2018 May 11.

Institute for Infectious Diseases and Zoonoses, LMU Munich, Germany; German Center for Infection Research (DZIF), Munich Partner Site, Germany.

Modified Vaccinia Virus Ankara (MVA) is a highly attenuated and replication-deficient virus serving as vaccine against infectious diseases. Here, we assessed the in vivo distribution of a recombinant MVA candidate vaccine against the Middle Eastern Respiratory Syndrome (MVA-MERS-S) in mice. Intramuscularly inoculated mice were necropsied at different time points and examined by histology, immunohistochemistry and real-time PCR. Read More

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Oncolytic Viral Therapy and the Immune System: A Double-Edged Sword Against Cancer.

Front Immunol 2018 26;9:866. Epub 2018 Apr 26.

Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.

Oncolytic viral therapy is a new promising strategy against cancer. Oncolytic viruses (OVs) can replicate in cancer cells but not in normal cells, leading to lysis of the tumor mass. Beside this primary effect, OVs can also stimulate the immune system. Read More

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April 2018
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Mechanism of vaccinia viral protein B14 mediated inhibition of IκB kinase β activation.

J Biol Chem 2018 May 10. Epub 2018 May 10.

Molecular and Structural Biochemistry, North Carolina State University, United States.

Activation of the IkB kinase β (IKKβ) is a central event in the NF-kB mediated canonical pro-inflammatory pathway. Numerous studies have reported that the oligomerization-mediated trans auto-phosphorylation of IKKβ is indispensable for itsphosphorylation leading to its activation and the IKKβ-mediated phosphorylation of substrates such as the IkB proteins. Moreover, IKKβ'sinteraction with NF-kB essential modifier (NEMO) is necessary for IKKβ activation. Read More

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Antigenicity of -Activated C-Kinase Antigen (LACK) in Human Peripheral Blood Mononuclear Cells, and Protective Effect of Prime-Boost Vaccination With pCI-neo-LACK Plus Attenuated LACK-Expressing Vaccinia Viruses in Hamsters.

Front Immunol 2018 23;9:843. Epub 2018 Apr 23.

WHO Collaborating Center for Leishmaniasis, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

-activated C-kinase antigen (LACK) is a highly conserved protein among species and is considered a viable vaccine candidate for human leishmaniasis. In animal models, prime-boost vaccination with LACK-expressing plasmids plus attenuated vaccinia viruses (modified vaccinia Ankara [MVA] and mutant M65) expressing LACK, has been shown to protect against cutaneous leishmaniasis (CL). Further, LACK demonstrated to induce the production of protective cytokines in patients with active CL or cured visceral leishmaniasis, as well as in asymptomatic individuals from endemic areas. Read More

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April 2018
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Executive summary of the Clinical Guidelines of Pharmacotherapy for Neuropathic Pain: second edition by the Japanese Society of Pain Clinicians.

J Anesth 2018 Jun 8;32(3):463-478. Epub 2018 May 8.

Pain Management Clinic, Shiga University of Medical Science Hospital, Otsu, Japan.

Neuropathic pain has a substantial effect on quality of life (QOL). The Japanese Society of Pain Clinicians (JSPC) has developed clinical guidelines of pharmacotherapy for neuropathic pain. These guidelines offer clarity on recommendations based on both the most recent scientific evidence and expert opinions. Read More

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A multi-antigenic MVA vaccine increases efficacy of combination chemotherapy against Mycobacterium tuberculosis.

PLoS One 2018 2;13(5):e0196815. Epub 2018 May 2.

Transgene SA, Infectious Diseases department, Centre d'Infectiologie, Bât Domilyon, Lyon, France.

Despite the existence of the prophylactic Bacille Calmette-Guérin (BCG) vaccine, infection by Mycobacterium tuberculosis (Mtb) remains a major public health issue causing up to 1.8 million annual deaths worldwide. Increasing prevalence of Mtb strains resistant to antibiotics represents an urgent threat for global health that has prompted a search for alternative treatment regimens not subject to development of resistance. Read More

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May 2018
2 Reads

Weak vaccinia virus-induced NK cell regulation of CD4 T cells is associated with reduced NK cell differentiation and cytolytic activity.

Virology 2018 06 30;519:131-144. Epub 2018 Apr 30.

Department of Pathology, University of Massachusetts Medical School, 368 Plantation Street, ASC9-2014E, Worcester, MA 01605, USA. Electronic address:

Natural killer (NK) cells control antiviral adaptive immune responses in mice during some virus infections, but the universality of this phenomenon remains unknown. Lymphocytic choriomeningitis virus (LCMV) infection of mice triggered potent cytotoxic activity of NK cells (NK) against activated CD4 T cells, tumor cells, and allogeneic lymphocytes. In contrast, NK cells activated by vaccinia virus (VACV) infection (NK) exhibited weaker cytolytic activity against each of these target cells. Read More

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June 2018
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A Novel System for Constructing a Recombinant Highly-Attenuated Vaccinia Virus Strain (LC16m8) Expressing Foreign Genes and Its Application for the Generation of LC16m8-Based Vaccines against Herpes Simplex Virus 2.

Jpn J Infect Dis 2018 05 27;71(3):229-233. Epub 2018 Apr 27.

Department of Virology 1, National Institute of Infectious Diseases.

A novel system was developed for generating highly attenuated vaccinia virus LC16m8 (m8, third-generation smallpox vaccine) that expresses foreign genes. The innovations in this system are its excisable selection marker, specificity of the integration site of a gene of interest, and easy identification of clones with a fluorescent signal. Using this system, recombinant m8s, which expressed herpes simplex virus 2 (HSV-2) glycoprotein B (gB)-, gD-, or both gB and gD (gB + gD), were generated, and their efficacy was evaluated. Read More

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Entry and Disassembly of Large DNA Viruses: Electron Microscopy Leads the Way.

J Mol Biol 2018 Jun 24;430(12):1714-1724. Epub 2018 Apr 24.

Ultra-structural Bio-Imaging (UBI), Center for Innovation and Technological Research (CITECH) and Department of Cell Biology and Infection, Institut Pasteur-28, rue du Dr. Roux, 75015 Paris, France. Electronic address:

Nucleocytoplasmic large DNA viruses are a steadily growing group of viruses that infect a wide range of hosts and are characterized by large particle dimensions and genome sizes. Understanding how they enter into the host cell and deliver their genome in the cytoplasm is therefore particularly intriguing. Here, we review the current knowledge on the entry of two of the best-characterized nucleocytoplasmic large DNA viruses: the poxvirus Vaccinia virus (VACV) and the giant virus Mimivirus. Read More

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Sialic Acid-Binding Lectin Reduces the Oncolytic Vaccinia Virus Induced Toxicity in a Glioblastoma Mouse Model.

Mar Drugs 2018 Apr 26;16(5). Epub 2018 Apr 26.

College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China.

Although oncolytic viruses provide attractive vehicles for cancer treatment, their adverse effects are largely ignored. In this work, rat C6 glioblastoma cells were subcutaneously xenografted into mice, and a thymidine kinase-deficient oncolytic vaccinia virus (oncoVV) induced severe toxicity in this model. However, oncoVV-HddSBL, in which a gene encoding sialic acid-binding lectin (HddSBL) was inserted into oncoVV, significantly prolonged the survival of mice as compared to the control virus. Read More

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Novel oncolytic chimeric orthopoxvirus causes regression of pancreatic cancer xenografts and exhibits abscopal effect at a single low dose.

J Transl Med 2018 Apr 26;16(1):110. Epub 2018 Apr 26.

Department of Surgery, Division of Surgical Oncology, City of Hope National Medical Center, 1500 Duarte Rd., Duarte, CA, 91010, USA.

Background: Pancreatic ductal adenocarcinoma (PDAC) has been increasing by 0.5% per year in the United States. PDAC portends a dismal prognosis and novel therapies are needed. Read More

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April 2018
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Effects of pre-existing orthopoxvirus-specific immunity on the performance of Modified Vaccinia virus Ankara-based influenza vaccines.

Sci Rep 2018 Apr 24;8(1):6474. Epub 2018 Apr 24.

Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, Rotterdam, The Netherlands.

The replication-deficient orthopoxvirus modified vaccinia virus Ankara (MVA) is a promising vaccine vector against various pathogens and has an excellent safety record. However, pre-existing vector-specific immunity is frequently suggested to be a drawback of MVA-based vaccines. To address this issue, mice were vaccinated with MVA-based influenza vaccines in the presence or absence of orthopoxvirus-specific immunity. Read More

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Genome-wide RNAi Screening to Identify Host Factors That Modulate Oncolytic Virus Therapy.

J Vis Exp 2018 04 3(134). Epub 2018 Apr 3.

Children's Hospital of Eastern Ontario (CHEO) Research Institute; Department of Biology, Microbiology and Immunology, University of Ottawa; Department of Pediatrics, University of Ottawa;

High-throughput genome-wide RNAi (RNA interference) screening technology has been widely used for discovering host factors that impact virus replication. Here we present the application of this technology to uncovering host targets that specifically modulate the replication of Maraba virus, an oncolytic rhabdovirus, and vaccinia virus with the goal of enhancing therapy. While the protocol has been tested for use with oncolytic Maraba virus and oncolytic vaccinia virus, this approach is applicable to other oncolytic viruses and can also be utilized for identifying host targets that modulate virus replication in mammalian cells in general. Read More

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Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?

Cell Mol Life Sci 2018 Jul 20;75(13):2375-2388. Epub 2018 Apr 20.

Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, 37007, Salamanca, Spain.

DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR). Read More

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July 2018
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The immunogenicity of recombinant vaccines based on modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host.

Antiviral Res 2018 Jun 18;154:132-139. Epub 2018 Apr 18.

The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK. Electronic address:

African horse sickness (AHS) is a lethal equine disease transmitted by Culicoides biting midges and caused by African horse sickness virus (AHSV). AHS is endemic to sub-Saharan Africa, but devastating outbreaks have been recorded periodically outside this region. The perceived risk of an AHS outbreak occurring in Europe has increased following the frequent epidemics caused in ruminants by bluetongue virus, closely related to AHSV. Read More

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June 2018
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Mutagenic repair of double-stranded DNA breaks in vaccinia virus genomes requires cellular DNA ligase IV activity in the cytosol.

J Gen Virol 2018 Jun 20;99(6):790-804. Epub 2018 Apr 20.

1​Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Poxviruses comprise a group of large dsDNA viruses that include members relevant to human and animal health, such as variola virus, monkeypox virus, cowpox virus and vaccinia virus (VACV). Poxviruses are remarkable for their unique replication cycle, which is restricted to the cytoplasm of infected cells. The independence from the host nucleus requires poxviruses to encode most of the enzymes involved in DNA replication, transcription and processing. Read More

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June 2018
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Manifold Roles of CCR7 and Its Ligands in the Induction and Maintenance of Bronchus-Associated Lymphoid Tissue.

Cell Rep 2018 Apr;23(3):783-795

Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. Electronic address:

The processes underlying the development and maintenance of tertiary lymphoid organs are incompletely understood. Using a Ccr7 knockout/knockin approach, we show that spontaneous bronchus-associated lymphoid tissue (BALT) formation can be caused by CCR7-mediated migration defects of dendritic cells (DCs) in the lung. Plt/plt mice that lack the CCR7 ligands CCL19 and CCL21-serine do not form BALT spontaneously because lung-expressed CCL21-leucine presumably suffices to maintain steady-state DC egress. Read More

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First-in-Human Randomized Controlled Trial of Mosaic HIV-1 Immunogens Delivered via a Modified Vaccinia Ankara Vector.

J Infect Dis 2018 Apr 13. Epub 2018 Apr 13.

Harvard Medical School, Boston, MA.

Background: Mosaic immunogens are bioinformatically engineered HIV-1 sequences designed to elicit clade independent coverage against globally circulating HIV-1 strains.

Methods: This Phase 1 double-blind, randomized, placebo-controlled trial enrolled healthy HIV uninfected adults who received two doses of a modified vaccinia Ankara (MVA) vectored HIV-1 bivalent mosaic immunogen vaccine or placebo on days 0 and 84. Two groups were enrolled: those who were HIV-1 vaccine naïve (N=15) and those who had received an HIV-1 vaccine four to six years earlier (Ad26. Read More

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Comparative sequence and structural analysis of Indian orf viruses based on major envelope immuno-dominant protein (F1L), an homologue of pox viral p35/H3 protein.

Gene 2018 Jul 12;663:72-82. Epub 2018 Apr 12.

Pox Virus Laboratory, Division of Virology, ICAR-Indian Veterinary Research Institute (IVRI), Mukteswar, 263138, Nainital (District), Uttarakhand, India.

Orf virus (ORFV), a member of the genus Parapoxvirus in the family Poxviridae, is the cause of orf, a highly contagious zoonotic viral disease that affects mainly sheep and goats. In the present study, the sequence and phylogenetic analysis of Indian ORFV isolates (n = 15) from natural outbreaks in sheep and goats belonging to different geographical regions were analysed on the basis of F1L gene along with homology modelling of F1L protein. Multiple sequence alignments revealed highly conserved C-terminus and heterogeneity of N-terminus region of F1L among all orf viruses studied. Read More

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July 2018
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Immunogenicity and safety of three consecutive production lots of the non replicating smallpox vaccine MVA: A randomised, double blind, placebo controlled phase III trial.

PLoS One 2018 13;13(4):e0195897. Epub 2018 Apr 13.

Bavarian Nordic GmbH, Martinsried, Germany.

Background: Modified Vaccinia Ankara (MVA) is a live, viral vaccine under advanced development as a non-replicating smallpox vaccine. A randomised, double-blind, placebo-controlled phase III clinical trial was conducted to demonstrate the humoral immunogenic equivalence of three consecutively manufactured MVA production lots, and to confirm the safety and tolerability of MVA focusing on cardiac readouts.

Methods: The trial was conducted at 34 sites in the US. Read More

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Proteotype profiling unmasks a viral signalling network essential for poxvirus assembly and transcriptional competence.

Nat Microbiol 2018 May 9;3(5):588-599. Epub 2018 Apr 9.

Institute of Molecular Systems Biology, Department of Biology, ETH Zurich, Zurich, Switzerland.

To orchestrate context-dependent signalling programmes, poxviruses encode two dual-specificity enzymes, the F10 kinase and the H1 phosphatase. These signalling mediators are essential for poxvirus production, yet their substrate profiles and systems-level functions remain enigmatic. Using a phosphoproteomic screen of cells infected with wild-type, F10 and H1 mutant vaccinia viruses, we systematically defined the viral signalling network controlled by these enzymes. Read More

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Inhibition of vaccinia virus replication by nitazoxanide.

Virology 2018 05 3;518:398-405. Epub 2018 Apr 3.

Divisions of Human Biology and Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, United States; Department of Microbiology, University of Washington, Seattle, WA 98115, United States; Department of Medicine, University of Washington, Seattle, WA 98115, United States. Electronic address:

Nitazoxanide (NTZ) is an FDA-approved anti-protozoal drug that inhibits several bacteria and viruses as well. However, its effect on poxviruses is unknown. Therefore, we investigated the impact of NTZ on vaccinia virus (VACV). Read More

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May 2018
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Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth.

Proc Natl Acad Sci U S A 2018 Apr 2;115(16):E3808-E3816. Epub 2018 Apr 2.

Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 23 Uppsala, Sweden;

The zinc finger CCCH-type containing 11A () gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Read More

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Immunogenicity and Protection Against Influenza H7N3 in Mice by Modified Vaccinia Virus Ankara Vectors Expressing Influenza Virus Hemagglutinin or Neuraminidase.

Sci Rep 2018 Mar 29;8(1):5364. Epub 2018 Mar 29.

Laboratory of DNA Viruses, Center for Biologics Evaluations and Research, Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD, 20993, USA.

Influenza subtypes such as H7 have pandemic potential since they are able to infect humans with severe consequences, as evidenced by the ongoing H7N9 infections in China that began in 2013. The diversity of H7 viruses calls for a broadly cross-protective vaccine for protection. We describe the construction of recombinant modified vaccinia virus Ankara (MVA) vectors expressing the hemagglutinin (HA) or neuraminidase (NA) from three H7 viruses representing both Eurasian and North American H7 lineages - A/mallard/Netherlands/12/2000 (H7N3), A/Canada/rv444/2004 (H7N3), and A/Shanghai/02/2013 (H7N9). Read More

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March 2018
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A single vaccination with non-replicating MVA at birth induces both immediate and long-term protective immune responses.

Vaccine 2018 04 27;36(18):2427-2434. Epub 2018 Mar 27.

Bavarian Nordic GmbH, Fraunhoferstrasse 13, D-82152 Martinsried, Germany. Electronic address:

Newborns are considered difficult to protect against infections shortly after birth, due to their ineffective immune system that shows quantitative and qualitative differences compared to adults. However, here we show that a single vaccination of mice at birth with a replication-deficient live vaccine Modified Vaccinia Ankara [MVA] efficiently induces antigen-specific B- and T-cells that fully protect against a lethal Ectromelia virus challenge. Protection was induced within 2 weeks and using genetically modified mice we show that this protection was mainly T-cell dependent. Read More

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April 2018
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Matrix-M™ adjuvant enhances immunogenicity of both protein- and modified vaccinia virus Ankara-based influenza vaccines in mice.

Immunol Res 2018 Apr;66(2):224-233

Novavax AB, Kungsgatan 109, SE-75318, Uppsala, Sweden.

Influenza viruses continuously circulate in the human population and escape recognition by virus neutralizing antibodies induced by prior infection or vaccination through accumulation of mutations in the surface proteins hemagglutinin (HA) and neuraminidase (NA). Various strategies to develop a vaccine that provides broad protection against different influenza A viruses are under investigation, including use of recombinant (r) viral vectors and adjuvants. The replication-deficient modified vaccinia virus Ankara (MVA) is a promising vaccine vector that efficiently induces B and T cell responses specific for the antigen of interest. Read More

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April 2018
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Baseline mapping of Lassa fever virology, epidemiology and vaccine research and development.

NPJ Vaccines 2018 20;3:11. Epub 2018 Mar 20.

4Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX USA.

Lassa fever (LF) is a zoonotic disease associated with acute and potentially fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the family . It is generally assumed that a single infection with LASV will produce life-long protective immunity. This suggests that protective immunity induced by vaccination is an achievable goal and that cell-mediated immunity may play a more important role in protection, at least following natural infection. Read More

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