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Kimberly McCoy, Masaki Uchida, Byeongdu Lee, Trevor Douglas
Bottom-up construction of mesoscale materials using biologically derived nanoscale building blocks enables engineering of desired physical properties using green production methods. Virus-like particles (VLPs) are exceptional building blocks due to their monodispersed sizes, geometric shapes, production ease, proteinaceous composition, and our ability to independently functionalize the interior and exterior interfaces. Here a VLP, derived from bacteriophage P22, is used as a building block for the fabrication of a Protein Macromolecular Framework (PMF); a tightly-linked 3D network of functional protein cages that exhibit long-range order and catalytic activity...
March 20, 2018: ACS Nano
Joris Koetsveld, Nadezhda M Kolyasnikova, Alex Wagemakers, Olga A Stukolova, Dieuwertje Hoornstra, Denis S Sarksyan, Marina G Toporkova, Anna J Henningsson, Dag Hvidsten, Wim Ang, Ram Dessau, Alexander E Platonov, Joppe W Hovius
OBJECTIVES: Borrelia miyamotoi disease (BMD) is an emerging tick-borne disease in the Northern hemisphere. Serodiagnosis by measuring antibodies against glycerophosphodiester-phosphodiesterase (GlpQ) is performed experimentally, but has not been extensively clinically validated. Since we have previously shown the differential expression of antigenic variable major proteins (Vmps) in B. miyamotoi, our aim was to study antibody responses against GlpQ and Vmps in PCR-proven BMD patients and controls...
March 14, 2018: Clinical Microbiology and Infection
Brianne J Lindsay, Michal M Bonar, Ian N Costas-Cancelas, Kristin Hunt, Alexander I Makarkov, Sabrina Chierzi, Connie M Krawczyk, Nathalie Landry, Brian J Ward, Isabelle Rouiller
Plant-made virus-like particle (VLP) vaccines that display wild-type influenza hemagglutinin (HA) are rapidly advancing through clinical trials. Produced by transient transfection of Nicotiana benthamiana, these novel vaccines are unusually immunogenic, eliciting both humoral and cellular responses. Here, we directly visualized VLPs bearing either HA trimers derived from strains A/California/7/2009 or A/Indonesia/5/05 using cryo-electron microscopy and determined the 3D organization of the VLPs using cryo-electron tomography...
March 14, 2018: Vaccine
Lina Rustanti, Hongping Jin, Dongsheng Li, Mary Lor, Haran Sivakumaran, David Harrich
Nullbasic is a mutant form of HIV-1 Tat that has strong ability to protect cells from HIV-1 replication by inhibiting three different steps of viral replication: reverse transcription, Rev export of viral mRNA from the nucleus to the cytoplasm and transcription of viral mRNA by RNA polymerase II. We previously showed that Nullbasic inhibits transduction of human cells including T cells by HIV-1-based lentiviral vectors. Here we investigated whether the Nullbasic antagonists huTat2 (a Tat targeting intrabody), HIV-1 Tat or Rev proteins or cellular DDX1 protein could improve transduction by a HIV-1 lentiviral vector conveying Nullbasic-ZsGreen1 to human T cells...
March 14, 2018: Virologica Sinica
Shengwei Zhang, Qi Cheng, Chenxi Luo, Yali Qin, Mingzhou Chen
Human parainfluenza virus type 3 is one of the main causes of lower respiratory illness in newborns and infants. The role of the matrix protein (M) in viral budding is extensively studied, but the effect of M on viral replication remains to be determined. Using an HPIV3 minigenome assay, we found that M reduced HPIV3 mingenome-encoded reporter activity even though it had an unspecific effect on the expression of cellular genes. Furthermore, the inhibition effect of M on viral RNA synthesis was proven to be independent of its virus-like particles (VLPs)' release ability...
March 11, 2018: Viruses
Daniel Enosi Tuipulotu, Natalie E Netzler, Jennifer H Lun, Jason M Mackenzie, Peter A White
Norovirus infections are a significant health and economic burden globally, accounting for hundreds of millions of cases of acute gastroenteritis every year. In the absence of an approved norovirus vaccine, there is an urgent need to develop antivirals to treat chronic infections, and provide prophylactic therapy to limit viral spread during epidemics and pandemics. Toll-like receptor (TLR) agonists have been explored widely for their antiviral potential and several are progressing through clinical trials for the treatment of human immunodeficiency virus (HIV), hepatitis B virus (HBV) and as adjuvants for norovirus virus-like particle (VLP) vaccines...
March 12, 2018: Antimicrobial Agents and Chemotherapy
JiaFeng Huang, BingQi Zeng, Dan Liu, RiBang Wu, Jiang Zhang, BinQiang Liao, HaiLun He, Fei Bian
Vibriolysin-like proteases (VLPs) are important virulence agents in the arsenal of Vibrio causing instant cytotoxic effects during infection. Most of Vibrio secreted VLPs show serious pathogenicity, while some species of Vibrio with VLPs are non-pathogenic, like Vibrio tasmaniensis and Vibrio pacinii. To investigate the relation between VLPs and Vibrio pathogenicity, one phylogenetic tree of VLPs was constructed and compared consensus sequences at the N-terminus of VLPs. Based on these results, VLPs were defined into nine phylogenetic clades...
March 3, 2018: Microbial Pathogenesis
Richard B S Roden, Peter L Stern
The discovery of genotype 16 as the prototype oncogenic human papillomavirus (HPV) initiated a quarter century of laboratory and epidemiological studies that demonstrated their necessary, but not sufficient, aetiological role in cervical and several other anogenital and oropharyngeal cancers. Early virus-induced immune deviation can lead to persistent subclinical infection that brings the risk of progression to cancer. Effective secondary prevention of cervical cancer through cytological and/or HPV screening depends on regular and widespread use in the general population, but coverage is inadequate in low-resource settings...
March 2, 2018: Nature Reviews. Cancer
Dale Christiansen, Linda Earnest-Silveira, Brendon Chua, Irene Boo, Heidi E Drummer, Branka Grubor-Bauk, Eric J Gowans, David C Jackson, Joseph Torresi
The development of an effective preventative hepatitis C virus (HCV) vaccine will reside, in part, in its ability to elicit neutralizing antibodies (NAbs). We previously reported a genotype 1a HCV virus like particle (VLP) vaccine that produced HCV specific NAb and T cell responses that were substantially enhanced by Toll-like receptor 2 (TLR2) agonists. We have now produced a quadrivalent genotype 1a/1b/2a/3a HCV VLP vaccine and tested the ability of two TLR2 agonists, R4 Pam2 Cys and E8 Pam2 Cys, to stimulate the production of NAb...
February 28, 2018: Viral Immunology
Nawras Ghanem, Manuel Trost, Laura Sanchez Fontanet, Hauke Harms, Antonis Chatzinotas, Lukas Y Wick
Phages (i.e. viruses infecting bacteria) are considered to be good indicators and tracers for fecal pollution, hydraulic flow or colloidal transport in the subsurface. They are typically quantified as total virus particles (VLP) or plaque forming units (PFU) of infectious phages. As transport may lead to phage deactivation, VLP quantification can overestimate the number of infectious phages. In contrast, PFU counts may underestimate the transport of total virus particles. Using PFU and tunable resistive pulse sensing-based counting for active and total phages, resp...
February 26, 2018: Environmental Science & Technology
Ashley L Marcinkiewicz, Ilva Lieknina, Svetlana Kotelovica, Xiuli Yang, Peter Kraiczy, Utpal Pal, Yi-Pin Lin, Kaspars Tars
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the US and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H (FH). To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds FH to inhibit complement activation on the cell surface...
2018: Frontiers in Immunology
Yu Zhou, Chao Zhang, Qingwei Liu, Sitang Gong, Lanlan Geng, Zhong Huang
Coxsackievirus A10 (CVA10) has emerged worldwide as one of the main pathogens of hand, foot, and mouth disease (HFMD) in recent years. However, there is currently no commercial vaccine available to prevent CVA10 infection. Here we report the development of a recombinant virus-like particle (VLP) based candidate vaccine for CVA10. Co-expression of the capsid protein precursor P1 and the protease 3CD of CVA10 in Pichia pastoris resulted in cleavage of P1 into three capsid subunit proteins VP0, VP1, and VP3. These three subunit proteins co-assembled into CVA10 VLPs, which were visualized as spherical particles with a diameter of ∼30 nm under electron microscope...
February 19, 2018: Antiviral Research
Xuanwei Ding, Dong Liu, George Booth, Wei Gao, Yuan Lu
As mimicking natural virus structures, virus-like particles (VLPs) have evolved to become a widely accepted technology used for humans which are safe, highly efficacious and profitable. Several remarkable advantages have been achieved to revolutionize the molecule delivery for diverse applications in nanotechnology, biotechnology, and medicine. Here, we review the rational structure design, manufacturing process, functionalization strategy, and emerging applications of VLPs. The situation and challenges in the VLP engineering, the key development orientation, and future applications have been discussed...
February 17, 2018: Biotechnology Journal
Anne-Marie C Andersson, Melanie Schwerdtfeger, Peter J Holst
Protection against chronic infections has necessitated the development of ever-more potent vaccination tools. HIV seems to be the most challenging foe, with a remarkable, poorly immunogenic and fragile surface glycoprotein and the ability to overpower the cell immune system. Virus-like-particle (VLP) vaccines have emerged as potent inducers of antibody and helper T cell responses, while replication-deficient viral vectors have yielded potent cytotoxic T cell responses. Here, we review the emerging concept of merging these two technologies into virus-like-vaccines (VLVs) for the targeting of HIV...
February 11, 2018: Vaccines
Diana Gabriela Valencia-Reséndiz, Giovanni Palomino-Vizcaino, Juana Virginia Tapia-Vieyra, María Luisa Benítez-Hess, Ana Gabriela Leija-Montoya, Luis Marat Alvarez-Salas
Human papillomavirus type 16 (HPV16) DNA has been found in ∼50% of cervical tumors worldwide. HPV infection starts with the binding of the virus capsid to heparan sulfate (HS) receptors exposed on the surface of epithelial basal layer keratinocytes. Previously, our group isolated a high-affinity RNA aptamer (Sc5c3) specific for HPV16 L1 virus-like particles (VLPs). In this study, we report the inhibition of HPV16 infection by Sc5c3 in a pseudovirus (PsVs) model. 293TT cells were infected by HPV16 PsVs containing the yellow fluorescent protein (YFP) as reporter gene...
February 13, 2018: Nucleic Acid Therapeutics
Pei Chen, Lei Zhang, Na Chang, Peidian Shi, Tian Gao, Lilin Zhang, Jinhai Huang
Porcine circovirus type 2 (PCV2) poses a genuine threat to pig industry. An effective vaccine production against the pandemic is desirable. The aim of this study was to construct recombination yeast strains with PCV2 Cap protein. We adopt to YeastFab Assembly method to synthesize transcriptional units in a single tube by piecing up promoter, open reading frame, and terminator in S. cerevisiae. Two yeast recombinants were successfully constructed using GPD and TEF2 promoters, respectively, to express PCV2 by secreting Cap protein in vitro...
February 7, 2018: Virus Genes
David Wetzel, Theresa Rolf, Manfred Suckow, Andreas Kranz, Andreas Barbian, Jo-Anne Chan, Joachim Leitsch, Michael Weniger, Volker Jenzelewski, Betty Kouskousis, Catherine Palmer, James G Beeson, Gerhard Schembecker, Juliane Merz, Michael Piontek
BACKGROUND: Chimeric virus-like particles (VLP) allow the display of foreign antigens on their surface and have proved valuable in the development of safe subunit vaccines or drug delivery. However, finding an inexpensive production system and a VLP scaffold that allows stable incorporation of diverse, large foreign antigens are major challenges in this field. RESULTS: In this study, a versatile and cost-effective platform for chimeric VLP development was established...
February 5, 2018: Microbial Cell Factories
Arianna Palladini, Susan Thrane, Christoph M Janitzek, Jessica Pihl, Stine B Clemmensen, Willem Adriaan de Jongh, Thomas M Clausen, Giordano Nicoletti, Lorena Landuzzi, Manuel L Penichet, Tania Balboni, Marianna L Ianzano, Veronica Giusti, Thor G Theander, Morten A Nielsen, Ali Salanti, Pier-Luigi Lollini, Patrizia Nanni, Adam F Sander
Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20-30% of invasive breast cancers. Monoclonal antibody therapy is effective in treating HER2-driven mammary carcinomas, but its utility is limited by high costs, side effects and development of resistance. Active vaccination may represent a safer, more effective and cheaper alternative, although the induction of strong and durable autoantibody responses is hampered by immune-tolerogenic mechanisms. Using a novel virus-like particle (VLP) based vaccine platform we show that directional, high-density display of human HER2 on the surface of VLPs, allows induction of therapeutically potent anti-HER2 autoantibody responses...
2018: Oncoimmunology
Elisabetta Bolli, John P O'Rourke, Laura Conti, Stefania Lanzardo, Valeria Rolih, Jayne M Christen, Giuseppina Barutello, Marco Forni, Federica Pericle, Federica Cavallo
Aggressive forms of breast cancer, such as Her2+ and triple negative breast cancer (TNBC), are enriched in breast cancer stem cells (BCSC) and have limited therapeutic options. BCSC represent a key cellular reservoir for relapse, metastatic progression and therapeutic resistance. Their ability to resist common cytotoxic therapies relies on different mechanisms, including improved detoxification. The cystine-glutamate antiporter protein xCT (SLC7A11) regulates cystine intake, conversion to cysteine and subsequent glutathione synthesis, protecting cells against oxidative and chemical insults...
2018: Oncoimmunology
Rupsa Basu, Lukai Zhai, Alice Contreras, Ebenezer Tumban
Zika virus (ZIKV) is a mosquito-borne flavivirus that has re-emerged and is associated with many debilitating clinical manifestations. Research is currently being conducted to develop a prophylactic vaccine against the virus; however, there has not been any licensed ZIKV vaccine. Recent studies have identified potential B-cell epitopes (amino acids 241-259, 294-315, 317-327, 346-361, 377-388 and 421-437) on the envelope protein of ZIKV, which could be explored to develop peptide vaccines against ZIKV infection...
January 30, 2018: Vaccine
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