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mRNA vaccine

Ma Michelle D Peñaranda, Ingvill Jensen, Linn G Tollersrud, Jack-Ansgar Bruun, Jorunn B Jørgensen
Fish immunology research is at a pivotal point with the increasing availability of functional immunoassays and major advances in omics approaches. However, studies on fish B cells and their distinct subsets remain a challenge due to the limited availability of differentially expressed surface markers. To address this constraint, cell surface proteome of Atlantic salmon IgM+ B cells were analyzed by mass spectrometry and compared to surface proteins detected from two adherent salmon head kidney cell lines, ASK and SSP-9...
2019: Frontiers in Immunology
Qiusheng Zhang, Binglian Xu, Jiajia Pan, Danyang Liu, Ruoxian Lv, Dongchun Yan
Grass carp reovirus (GCRV) is one of the most serious pathogens threatening grass carp (Ctenopharyngodon idellus) production and results in high mortality in China. VP7 from GCRV is involved in viral infection and could be suitable for developing vaccines for the control of GCRV infection. To obtain a genetically engineered vaccine and a plant-based oral vaccine and to evaluate their immune efficacy as an oral vaccine against GCRV, cholera toxin B subunit (CTB) of Vibrio cholerae fused to VP7 (CTB-VP7) was transformed into BL21(DE3) for expression...
February 9, 2019: Protein Expression and Purification
Chunhe Guo, Zhenbang Zhu, Piao Yu, Xiaoxiao Zhang, Wenjuan Dong, Xiaoying Wang, Yaosheng Chen, Xiaohong Liu
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen and causes significant economic losses to the swine industry worldwide each year. Current vaccination strategies do not effectively prevent and control the virus. Consequently, it is necessary to develop novel antiviral strategies. Carrageenan, extracted from marine red algae, exhibits anti-coagulant, anti-tumor, anti-virus and immunomodulatory activities. METHODS: We investigate the inhibitory effect of iota-carrageenan (CG) on PRRSV strain CH-1a via antiviral assay and viral binding, entry and release assays...
February 12, 2019: Antiviral Therapy
Rein Verbeke, Ine Lentacker, Karine Breckpot, Jonas Janssens, Serge Van Calenbergh, Stefaan C De Smedt, Heleen Dewitte
Messenger RNA encoding tumor antigens has the potential to evoke effective antitumor immunity. This study reports on a nanoparticle platform, named mRNA Galsomes, that successfully co-delivers nucleoside-modified antigen-encoding mRNA and the glycolipid antigen and immunopotentiator α-Galactosylceramide (α-GC) to antigen-presenting cells after intravenous administration. By co-formulating low doses of α-GC, mRNA Galsomes induce a pluripotent innate and adaptive tumor-specific immune response in mice, with invariant natural killer T cells (iNKT) as a driving force...
February 11, 2019: ACS Nano
Qi Wang, Alanna Vossen, Yasuhiro Ikeda, Patricia Devaux
Induced pluripotent stem cells (iPSCs) provide a unique platform for individualized cell therapy approaches. Currently, episomal DNA, mRNA, and Sendai virus-based RNA reprogramming systems are widely used to generate iPSCs. However, they all rely on the use of multiple (three to six) components (vectors/plasmids/mRNAs) leading to the production of partially reprogrammed cells, reducing the efficiency of the systems. We produced a one-cycle measles virus (MV) vector by substituting the viral attachment protein gene with the green fluorescent protein (GFP) gene...
February 4, 2019: Gene Therapy
Susu Liu, Yang Du, Xiuzhen Sheng, Xiaoqian Tang, Jing Xing, Webin Zhan
In the present work, the polymeric immunoglobulin receptor-like (pIgRL) from flounder (Paralichthys olivaceus) was firstly cloned and identified. The full length cDNA of flounder pIgRL was of 1393 bp including an open reading frame of 1053 bp, and the deduced pIgRL sequence encoded 350 amino acids, with a predicted molecular mass of 39 kDa. There were two immunoglobulin-like domains in flounder pIgRL. In healthy flounder, the transcriptional level of pIgRL was detected in different tissues by real-time PCR, showing the highest level in the skin and gills, and higher levels in the spleen and hindgut...
January 30, 2019: Fish & Shellfish Immunology
Muhammad Irfan Malik, Mohsin Nawaz, Ibrahim A Hassan, Houshuang Zhang, Haiyan Gong, Jie Cao, Yongzhi Zhou, Jinlin Zhou
BACKGROUND: Tick saliva contains many bioactive molecules that are involved in attachment to the host, blood-feeding and transmission of pathogens. MicroRNAs (miRNAs) are a class of short non-coding RNAs with a length of 19-24 nucleotides. They act as regulators of gene expression by binding to their target mRNA at the post-transcriptional level and control a variety of cellular functions, including regulation of growth, metabolism and development. The detection and characterizations of miRNAs from tick saliva may help explain the molecular mechanisms involved in the interaction between ticks, pathogens and hosts...
February 1, 2019: Parasites & Vectors
Zahra Payandeh, Maral Yarahmadi, Ziba Nariman-Saleh-Fam, Vahideh Tarhriz, Maryam Islami, Abdolreza Mehdinavaz Aghdam, Shirin Eyvazi
Melanoma is the most serious type of skin cancer which develops from the occurrence of genetic mutations in the melanocytes. Based on the features of melanoma tumors such as location, genetic profile and stage, there are several therapeutic strategies including surgery, chemotherapy, and radiotherapy. However, because of the appearance resistance mechanisms, the efficiency of these treatments strategies may be reduced. It has been demonstrated that therapeutic monoclonal antibodies can improve the efficiency of melanoma therapies...
January 31, 2019: Journal of Cellular Physiology
Junru Cui, Caitlin M O'Connell, Antonio Costa, Yan Pan, Joan A Smyth, Paulo H Verardi, Diane J Burgess, Herbert J Van Kruiningen, Antonio E Garmendia
Porcine reproductive and respiratory syndrome virus (PRRSV), is a highly mutable RNA virus that affects swine worldwide and its control is very challenging due to its formidable heterogeneity in the field. In the present study, DNA vaccines constructed with PRRSV GP5-Mosaic sequences were complexed to cationic liposomes and administered to experimental pigs by intradermal and intramuscular injection, followed by three boosters 14, 28 and 42 days later. The GP5-Mosaic vaccine thus formulated was immunogenic and induced protection from challenge in vaccinated pigs comparable to that induced by a wild type (VR2332) GP5 DNA vaccine (GP5-WT)...
2019: PloS One
Wentao Zhu, Yanqi Zhang, Jiacheng Zhang, Gailing Yuan, Xiaoling Liu, Taoshan Ai, Jianguo Su
The yellow catfish (Pelteobagrus fulvidraco) is an economically important fish in China, but Edwardsiella ictaluri, an intracellular pathogenic bacterium, causes great losses to the culture industry. Currently, vaccination is the most promising strategy to combat the infectious diseases, while adjuvant can provide effective assistant for vaccines to enhance immune responses. In the present study, inactivated E. ictaluri vaccine was prepared, then Astragalus polysaccharides (APS), chitosan and poly(I:C) were employed as adjuvants to evaluate the effect on boosting immune responses and protecting yellow catfish against E...
January 25, 2019: Fish & Shellfish Immunology
Vahid Bagheri, Mohammad Reza Abbaszadegan, Bahram Memar, Mohammad Reza Motie, Mahdi Asadi, Reihaneh Alsadat Mahmoudian, Mehran Gholamin
Gastric cancer (GC) as the third most common cause of cancer-associated mortality worldwide is one of the cancers with very high heterogeneity. Cancer stem cells (CSCs) as a small subset of cancer cells in solid tumors with the self-renewal, differentiation and tumorigenic ability are responsible for tumor initiation, progression, recurrence, metastasis, and resistance to current treatments. Therefore, eradication of CSCs is very vital to cure cancer. Here, we first isolated and identified sphere-forming cells in tumor tissue from four GC patients and then analyzed T cell responses induced by monocyte-derived dendritic cells (DCs) loaded with total mRNA of sphere-forming cells in terms of interferon-gamma (IFN-γ) gene expression and specific cytotoxicity...
January 11, 2019: Life Sciences
Alexandra G Orlandini von Niessen, Marco A Poleganov, Corina Rechner, Arianne Plaschke, Lena M Kranz, Stephanie Fesser, Mustafa Diken, Martin Löwer, Britta Vallazza, Tim Beissert, Valesca Bukur, Andreas N Kuhn, Özlem Türeci, Ugur Sahin
Synthetic mRNA has emerged as a powerful tool for the transfer of genetic information, and it is being explored for a variety of therapeutic applications. Many of these applications require prolonged intracellular persistence of mRNA to improve bioavailability of the encoded protein. mRNA molecules are intrinsically unstable and their intracellular kinetics depend on the UTRs embracing the coding sequence, in particular the 3' UTR elements. We describe here a novel and generally applicable cell-based selection process for the identification of 3' UTRs that augment the expression of proteins encoded by synthetic mRNA...
December 18, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Huahua He, Chao Zhai, Meng Mei, Yi Rao, Yao Liu, Fei Wang, Lixin Ma, Zhengbing Jiang, Guimin Zhang, Li Yi
Porcine interferon-α (pIFN-α) could be used as the vaccine adjuvant to enhance the antiviral ability of porcine in swine industry. In here, a combinational strategy integrating codon optimization, multiple gene insertion, strong AOX1 promoter, and efficient secretion signal sequence was developed to obtain high-level secreted pIFN-α in Pichia pastoris GS115. The codon optimized pIFN-α shared 76% sequence identity with the original pIFN-α, which was inserted into the P. pastoris genome under AOX1d1-2x201 promoter and MF4I secretion sequence...
March 2019: Enzyme and Microbial Technology
Mashooq Ahmad Dar, Uneeb Urwat, Syed Mudasir Ahmad, Raashid Ahmad, Zahid Amin Kashoo, Tanveer Ali Dar, Shakil Ahmad Bhat, Peerzada Tajamul Mumtaz, Nadeem Shabir, Riaz Ahmad Shah, Mohammad Heidari
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a primary avian pathogen responsible for severe intestinal pathology in younger chickens and economic losses to poultry industry. Furthermore, S. Typhimurium is also able to cause infection in humans, characterized by acute gastrointestinal disease. A study was conducted to investigate antibody response and expression kinetics of interferon gamma (IFNγ), interleukin (IL-12, and IL-18) genes in broiler chicken at 0, 1, 3, 5, 7, 9, 11, 13, and 15 D post infection following experimental infection of S...
December 28, 2018: Poultry Science
Zhichao Xu, Huiling Zhong, Songjian Huang, Qingfeng Zhou, Yunping Du, Li Chen, Chunyi Xue, Yongchang Cao
Porcine deltacoronavirus (PDCoV) is a newly identified swine enteropathogenic coronavirus that causes watery diarrhea in piglets and results in significant economic losses to the pig industry. Currently there are no effective treatments or vaccines for PDCoV. In particular, the pathogenesis of PDCoV infection is still largely unknown. In this study, we reported that inoculating conventional weaned piglets with 1 × 109 TCID50 of the PDCoV CHN-GD-2016 strain by oral feeding could cause severe diarrhea. Virus RNA was detected in rectal swabs from 1 to 7 days post inoculation...
January 2019: Veterinary Microbiology
X Zeng, H Gu, Y Cheng, K-R Jia, D Liu, Y Yuan, Z-F Chen, L-S Peng, Q-M Zou, Y Shi
OBJECTIVES: Acinetobacter baumannii can cause severe nosocomial and community-acquired pneumonia. To study the pathogenesis of A. baumannii and to develop new treatments, appropriate mouse models are needed. Most reported mouse models of pulmonary A. baumannii infection are non-lethal or require mouse immunosuppression to enhance infection. These models are not suitable for studying host immune responses or evaluating immunotherapies. METHODS: The virulence of 30 clinical isolates was assessed in mice...
December 22, 2018: Clinical Microbiology and Infection
Seisuke Tajimi, Masakazu Kondo, Teruyuki Nakanishi, Takahiro Nagasawa, Miki Nakao, Tomonori Somamoto
Although a previous study using ginbuna crucian carp suggested that cell-mediated immunity can be induced by the oral administration of inactivated viruses, which are exogenous antigens, there is no direct evidence that CD8+ cytotoxic T cells (CTLs) in teleost fish are generated by vaccination with exogenous antigens. In the present study, we investigated whether antigen-specific CD8+ CTLs in ginbuna crucian carp can be elicited by intestinal immunization with an exogenous antigen without any adjuvant. The IFNγ-1 and T-bet mRNA expressions were up-regulated in intestinal leukocytes following the administration of formalin-inactivated crucian hematopoietic necrosis virus (FI-CHNV), whereas the down-regulation of these genes was observed in kidney leukocytes...
December 21, 2018: Developmental and Comparative Immunology
Emmeline L Blanchard, Kristin H Loomis, Sushma M Bhosle, Daryll Vanover, Patrick Baumhof, Bruno Pitard, Chiara Zurla, Philip J Santangelo
The characterization of innate immune activation is crucial for vaccine and therapeutic development, including RNA-based vaccines, a promising approach. Current measurement methods quantify type I interferon and inflammatory cytokine production, but they do not allow for the isolation of individual pathways, do not provide kinetic activation or spatial information within tissues, and cannot be translated into clinical studies. Here we demonstrated the use of proximity ligation assays (PLAs) to detect pattern recognition receptor (PRR) activation in cells and in tissue samples...
November 20, 2018: Molecular Therapy. Nucleic Acids
Laura A VanBlargan, Sunny Himansu, Bryant M Foreman, Gregory D Ebel, Theodore C Pierson, Michael S Diamond
Powassan virus (POWV) is an emerging tick-transmitted flavivirus that circulates in North America and Russia. Up to 5% of deer ticks now test positive for POWV in certain regions of the northern United States. Although POWV infections cause life-threatening encephalitis, there is no vaccine or countermeasure available for prevention or treatment. Here, we developed a lipid nanoparticle (LNP)-encapsulated modified mRNA vaccine encoding the POWV prM and E genes and demonstrated its immunogenicity and efficacy in mice following immunization with one or two doses...
December 18, 2018: Cell Reports
Ria Lassaunière, Maria Paximadis, Osman Ebrahim, Richard E Chaisson, Neil A Martinson, Caroline T Tiemessen
In the HIV-1 Thai RV144 vaccine trial-the only trial to demonstrate any vaccine efficacy to date-a three-variant haplotype within the Fc gamma receptor 2C gene (FCGR2C) modified the risk of HIV-1 acquisition. A similar vaccine regimen is currently being evaluated in South Africa in the HVTN702 trial, where the predominant population is polymorphic for only a single variant in the haplotype, c.134-96C>T. To investigate the significance of c.134-96C>T in HIV-specific immunity in South Africans, this study assessed its role in HIV-1 disease progression...
December 19, 2018: Genes and Immunity
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