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mRNA vaccine

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https://www.readbyqxmd.com/read/28102931/the-impact-of-hpv-type-on-colposcopy-performance-in-women-offered-hpv-immunisation-in-a-catch-up-vaccine-programme-a-two-centre-observational-study
#1
Ami Munro, Collette Gillespie, Seonaidh Cotton, Camille Busby-Earle, Kim Kavanagh, Kate Cuschieri, Heather Cubie, Chris Robertson, Louise Smart, Kevin Pollock, Catherine Moore, Timothy Palmer, Margaret E Cruickshank
OBJECTIVE: To determine if HPV immunisation has affected the prevalence of HPV genotypes and colposcopic features of CIN in young women referred for colposcopy. DESIGN: A two-centre observational study including vaccinated and unvaccinated women. SETTING: Colposcopy clinics serving two health regions in Scotland, UK. POPULATION: 361 women aged 20-25 years attending colposcopy following an abnormal cervical cytology result at routine cervical screening...
January 19, 2017: BJOG: An International Journal of Obstetrics and Gynaecology
https://www.readbyqxmd.com/read/28096968/a-novel-atheroprotective-role-of-mf59-like-adjuvant-when-co-administered-with-cetp-vaccine-in-rabbit-model-of-atherosclerosis
#2
Tamara Aghebati, Amir Hooshang Mohammadpour, Mohammad Afshar, Mahmoud Reza Jaafari, Khalil Abnous, Saeed Nazemi, Sobhan Issazadeh, Saeed Hashemzadeh, Mohammad Zare, Ali Badiee
OBJECTIVES: In this study, for the first time, MF59 adjuvant was used to develop a cholesteryl ester transfer protein (CETP) vaccine. The efficacy of the vaccine was compared with the efficacy of CETP vaccine formulated with Alum/CpG, the formulation that its immunogenicity has been already demonstrated in rabbit and mice. MATERIALS AND METHODS: Tetanus toxoid- CETP peptide (TT-CETP) was mixed with Alum/CpG or MF59-like and administered subcutaneously for total five times in rabbit model of atherosclerosis...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28095348/immune-transcriptome-reveals-the-mincle-c-type-lectin-receptor-acts-as-a-partial-replacement-for-tlr4-in-lipopolysaccharide-mediated-inflammatory-response-in-barramundi-lates-calcarifer
#3
Emmanuelle Zoccola, Stuart Kellie, Andrew C Barnes
Fish represent the most diverse and abundant extant vertebrate infraclass. They are also one of the earliest divergent phyla with adaptive immunity based on antigen recognition by MHC and immunoglobulin. The aquaculture industry, which currently provides more than half of the fish for human consumption globally, has successfully exploited the adaptive immune system of fish through mass vaccination programs. However, vaccination against highly diverse antigens, mostly carbohydrates, such as capsular polysaccharides and lipopolysaccharide (LPS) is challenging...
January 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28094775/nanotechnologies-in-delivery-of-mrna-therapeutics-using-nonviral-vector-based-delivery-systems
#4
REVIEW
S Guan, J Rosenecker
Due to its safe and effective protein expression profile, in vitro transcribed messenger RNA (IVT-mRNA) represents a promising candidate in the development of novel therapeutics for genetic diseases, vaccines or gene editing strategies, especially when its inherent shortcomings (e.g. instability and immunogenicity) have been partially addressed via structural modifications. However, numerous unsolved technical difficulties in successful in vivo delivery of IVT-mRNA have greatly hindered the applications of IVT-mRNA in clinical development...
January 17, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28091958/identification-and-anticoagulant-activity-of-a-novel-kunitz-type-protein-ha11-from-the-salivary-gland-of-the-tick-hyalomma-asiaticum
#5
Houshuang Zhang, Ruiqiong Qiao, Haiyan Gong, Jie Cao, Yongzhi Zhou, Jinlin Zhou
Kunitz/bovine pancreatic trypsin inhibitor proteins are abundant in the salivary glands of ticks and perform multiple functions in blood feeding, including inhibiting blood coagulation, regulating host blood supply and disrupting host angiogenesis. In this study, we identified a novel gene designated HA11 (Hyalomma asiaticum 11 kDa protein) from the salivary gland of the tick H. asiaticum. HA11 is encoded by a gene with an open reading frame of 306 bp that is translated into a deduced 101 amino acid 11 kDa protein that shares 27% sequence identity with a Kunitz-like protease inhibitor precursor in Amblyomma variegatum...
January 13, 2017: Experimental & Applied Acarology
https://www.readbyqxmd.com/read/28087198/cloning-characterization-and-transmission-blocking-potential-of-midgut-carboxypeptidase-a-in-anopheles-stephensi
#6
V VenkatRao, Surendra K Kumar, P Sridevi, Vijaykumar Yogesh Muley, R K Chaitanya
Transmission-blocking vaccines (TBV) interrupt malaria parasite transmission and hence form an important component for malaria eradication. Mosquito midgut exopeptidases such as aminopeptidase N & carboxypeptidase B have demonstrated TBV potential. In the present study, we cloned and characterized carboxypeptidase A (CPA) from the midgut of an important malarial vector, Anopheles stephensi. ClustalW amino acid alignment and in silico 3-dimensional structure analysis of CPA predicted the presence of active sites involved in zinc and substrate binding that are conserved among all the known mosquito species...
January 10, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28069945/charge-altering-releasable-transporters-carts-for-the-delivery-and-release-of-mrna-in-living-animals
#7
Colin J McKinlay, Jessica R Vargas, Timothy R Blake, Jonathan W Hardy, Masamitsu Kanada, Christopher H Contag, Paul A Wender, Robert M Waymouth
Functional delivery of mRNA to tissues in the body is key to implementing fundamentally new and potentially transformative strategies for vaccination, protein replacement therapy, and genome editing, collectively affecting approaches for the prevention, detection, and treatment of disease. Broadly applicable tools for the efficient delivery of mRNA into cultured cells would advance many areas of research, and effective and safe in vivo mRNA delivery could fundamentally transform clinical practice. Here we report the step-economical synthesis and evaluation of a tunable and effective class of synthetic biodegradable materials: charge-altering releasable transporters (CARTs) for mRNA delivery into cells...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28069074/a-next-generation-microarray-further-reveals-stage-enriched-gene-expression-pattern-in-the-blood-fluke-schistosoma-japonicum
#8
Pengfei Cai, Shuai Liu, Xianyu Piao, Nan Hou, Hong You, Donald P McManus, Qijun Chen
BACKGROUND: Schistosomiasis is caused by infection with blood flukes of the genus Schistosoma, and ranks, in terms of disability-adjusted life years (DALYs), as the third most important neglected tropical disease. Schistosomes have several discrete life stages involving dramatic morphological changes during their development, which require subtle gene expression modulations to complete the complex life-cycle. RESULTS: In the current study, we employed a second generation schistosome DNA chip printed with the most comprehensive probe array for studying the Schistosoma japonicum transcriptome, to explore stage-associated gene expression in different developmental phases of S...
January 10, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28065477/quantitative-analysis-of-the-yield-of-avian-h7-influenza-virus-haemagglutinin-protein-produced-in-silkworm-pupae-with-the-use-of-the-codon-optimized-dna-a-possible-oral-vaccine
#9
Kuniaki Nerome, Sayaka Matsuda, Kenichi Maegawa, Shigeo Sugita, Kazumichi Kuroda, Kazunori Kawasaki, Reiko Nerome
In this study, we aimed to quantitatively compare the increased production of three H7 influenza virus-like particle (VLP) haemagglutinin (HA) with the use of a codon-optimized single HA gene in silkworm pupae. Recombinant baculovirus (Korea H7-BmNPV) could produce 0.40 million HA units per pupa, corresponding to 1832μg protein. The yield of the HA produced in larva was estimated to be approximately 0.31 million HA units per larva, and there were no significant differences between the three HA proteins. We could establish efficient recovery system of HA production in larvae and pupae with the use of three cycles sonication methods...
January 5, 2017: Vaccine
https://www.readbyqxmd.com/read/28049494/adjuvant-effects-of-a-sequence-engineered-mrna-vaccine-translational-profiling-demonstrates-similar-human-and-murine-innate-response
#10
Darin K Edwards, Edith Jasny, Heesik Yoon, Nigel Horscroft, Brian Schanen, Tanya Geter, Mariola Fotin-Mleczek, Benjamin Petsch, Vaughan Wittman
BACKGROUND: Prophylactic and therapeutic vaccines often depend upon a strong activation of the innate immune system to drive a potent adaptive immune response, often mediated by a strong adjuvant. For a number of adjuvants immunological readouts may not be consistent across species. METHODS: In this study, we evaluated the innate immunostimulatory potential of mRNA vaccines in both humans and mice, using a novel mRNA-based vaccine encoding influenza A hemagglutinin of the pandemic strain H1N1pdm09 as a model...
January 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28049151/modulation-of-microrna-mrna-target-pairs-by-human-papillomavirus-16-oncoproteins
#11
Mallory E Harden, Nripesh Prasad, Anthony Griffiths, Karl Munger
: The E6 and E7 proteins are the major oncogenic drivers encoded by high-risk human papillomaviruses (HPVs). While many aspects of the transforming activities of these proteins have been extensively studied, there are fewer studies that have investigated how HPV E6/E7 expression affects the expression of cellular noncoding RNAs. The goal of our study was to investigate HPV16 E6/E7 modulation of cellular microRNA (miR) levels and to determine the potential consequences for cellular gene expression...
January 3, 2017: MBio
https://www.readbyqxmd.com/read/28005579/spontaneous-activation-of-antigen-presenting-cells-by-genes-encoding-truncated-homo-oligomerizing-derivatives-of-cd40
#12
Noam Levin, Aviad Pato, Gal Cafri, Galit Eisenberg, Tamar Peretz, Alon Margalit, Michal Lotem, Gideon Gross
The interaction between the CD40 receptor on antigen-presenting cells (APCs) and its trimeric ligand on CD4 T cells is essential for the initiation and progression of the adaptive immune response. Here we undertook to endow CD40 with the capacity to trigger spontaneous APC activation through ligand-independent oligomerization. To this end we exploited the GCN4 yeast transcriptional activator, which contains a leucine zipper DNA-binding motif that induces homophilic interactions. We incorporated GCN4 variants forming homodimers, trimers, or tetramers at the intracellular domain of human and mouse CD40 and replaced the extracellular portion with peptide-β2m or other peptide tags...
December 21, 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27999747/immune-response-and-long-term-clinical-outcome-in-advanced-melanoma-patients-vaccinated-with-tumor-mrna-transfected-dendritic-cells
#13
Jon Amund Kyte, Steinar Aamdal, Svein Dueland, Stein Sæbøe-Larsen, Else Marit Inderberg, Ulf Erik Madsbu, Eva Skovlund, Gustav Gaudernack, Gunnar Kvalheim
The most effective anticancer immune responses are probably directed against patient-specific neoantigens. We have developed a melanoma vaccine targeting this individual mutanome based on dendritic cells (DCs) loaded with autologous tumor-mRNA. Here, we report a phase I/II trial evaluating toxicity, immune response and clinical outcome in 31 metastatic melanoma patients. The first cohort (n = 22) received the vaccine without any adjuvant; the next cohort (n = 9) received adjuvant IL2. Each subject received four weekly intranodal or intradermal injections, followed by optional monthly vaccines...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27987154/considerations-for-producing-mrna-vaccines-for-clinical-trials
#14
Andreas Schmid
The approval of clinical trials by the competent authorities requires comprehensive quality documentation on the new drug to be used on the clinical trial participant. In the EU quality data is summarized as Investigational Medicinal Product Dossier (IMPD), in the USA as Investigational New Drug (IND) Application. For that, several preconditions concerning production, quality control, and assurance have to be fulfilled. Here, specific requirements related to mRNA vaccines are addressed on the basis of European standards...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27987153/discovery-and-subtyping-of-neo-epitope-specific-t-cell-responses-for-cancer-immunotherapy-addressing-the-mutanome
#15
Mustafa Diken, Mathias Vormehr, Christian Grunwitz, Sebastian Kreiter, Özlem Türeci, Ugur Sahin
Cancer accumulates 10s to 1000s of genomic mutations of which a fraction is immunogenic and may serve as an Achilles' heel of tumor cells. Mutation-specific T cells can recognize these antigens and destroy malignant cells. Strategies to immunotherapeutically address individual tumor mutations employing peptide or mRNA based vaccines are now actively investigated in mice and humans. An important step of determining the therapeutic potential of a mutanome vaccine is the detection of mutation reactive T-cell responses...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27987152/the-european-regulatory-environment-of-rna-based-vaccines
#16
Thomas Hinz, Kajo Kallen, Cedrik M Britten, Bruno Flamion, Ulrich Granzer, Axel Hoos, Christoph Huber, Samir Khleif, Sebastian Kreiter, Hans-Georg Rammensee, Ugur Sahin, Harpreet Singh-Jasuja, Özlem Türeci, Ulrich Kalinke
A variety of different mRNA-based drugs are currently in development. This became possible, since major breakthroughs in RNA research during the last decades allowed impressive improvements of translation, stability and delivery of mRNA. This article focuses on antigen-encoding RNA-based vaccines that are either directed against tumors or pathogens. mRNA-encoded vaccines are developed both for preventive or therapeutic purposes. Most mRNA-based vaccines are directly administered to patients. Alternatively, primary autologous cells from cancer patients are modified ex vivo by the use of mRNA and then are adoptively transferred to patients...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27987151/enhanced-delivery-of-dna-or-rna-vaccines-by-electroporation
#17
Kate E Broderick, Laurent M Humeau
Nucleic acid vaccines are a next-generation branch of vaccines which offer major benefits over their conventional protein, bacteria, or viral-based counterparts. However, to be effective in large mammals and humans, an enhancing delivery technology is required. Electroporation is a physical technique which results in improved delivery of large molecules through the cell membrane. In the case of plasmid DNA and mRNA, electroporation enhances both the uptake and expression of the delivered nucleic acids. The muscle is an attractive tissue for nucleic acid vaccination in a clinical setting due to the accessibility and abundance of the target tissue...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27987150/adjuvant-enhanced-mrna-vaccines
#18
Lukasz Bialkowski, Kevin Van der Jeught, Dries Renmans, Alexia van Weijnen, Carlo Heirman, Marleen Keyaerts, Karine Breckpot, Kris Thielemans
Recent advances in molecular biology have led to dramatic enhancement of the stability of in vitro transcribed (IVT) messenger RNA (mRNA) and improvement in its translational efficacy. Nowadays, mRNA-based vaccines represent a promising approach in the field of anticancer immunotherapy, gaining attention over the earlier-established bacteria-, virus-, or cell-based vaccination approaches. Here, we present the experimental procedures employed in our laboratory to induce anticancer immune responses in different murine tumor models using IVT mRNA encoding for immune activation signals and antigens of interest...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27987149/electroporation-of-mrna-as-universal-technology-platform-to-transfect-a-variety-of-primary-cells-with-antigens-and-functional-proteins
#19
Kerstin F Gerer, Stefanie Hoyer, Jan Dörrie, Niels Schaft
Electroporation (EP) of mRNA into human cells is a broadly applicable method to transiently express proteins of choice in a variety of different cell types. We have spent more than a decade to optimize and adapt this method, first for antigen-loading of dendritic cells (DCs), and subsequently for T cells, B cells, bulk PBMCs, and several cell lines. In this regard, antigens were introduced, processed, and presented in context of MHC class I and II. Next to that, functional proteins like adhesion receptors, T-cell receptors (TCRs), chimeric antigen receptors (CARs), constitutively active signal transducers, and others were successfully expressed...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27987147/measuring-the-adjuvant-activity-of-rna-vaccines
#20
Norbert Pardi, Drew Weissman
mRNA has recently arisen as a promising new drug class with the potential to be applied to various therapeutic modalities, including protein replacement and vaccination against cancer and infectious diseases. Numerous approaches have been pursued to develop potent mRNA vaccines, many of them have proved to be successful and have already entered human clinical trials. RNA, especially in vitro transcribed, is extremely immunogenic as it induces innate immune responses through the activation of a variety of pattern recognition receptors...
2017: Methods in Molecular Biology
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