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mRNA vaccine

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https://www.readbyqxmd.com/read/28436620/arginine-rich-peptide-based-mrna-nanocomplexes-efficiently-instigate-cytotoxic-t-cell-immunity-dependent-on-the-amphipathic-organization-of-the-peptide
#1
Vimal K Udhayakumar, Ans De Beuckelaer, Joanne McCaffrey, Cian M McCrudden, Jonathan L Kirschman, Daryll Vanover, Lien Van Hoecke, Kenny Roose, Kim Deswarte, Bruno G De Geest, Stefan Lienenklaus, Philip J Santangelo, Johan Grooten, Helen O McCarthy, Stefaan De Koker
To date, the mRNA delivery field has been heavily dominated by lipid-based systems. Reports on the use of nonlipid carriers for mRNA delivery in contrast are rare in the context of mRNA vaccination. This paper describes the potential of a cell-penetrating peptide containing the amphipathic RALA motif to deliver antigen-encoding mRNA to the immune system. RALA condenses mRNA into nanocomplexes that display acidic pH-dependent membrane disruptive properties. RALA mRNA nanocomplexes enable mRNA escape from endosomes and thereby allow expression of mRNA inside the dendritic cell cytosol...
April 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28432975/vaccination-strategies-against-zika-virus
#2
REVIEW
Estefania Fernandez, Michael S Diamond
The epidemic emergence of Zika virus (ZIKV) in 2015-2016 has been associated with congenital malformations and neurological sequela. Current efforts to develop a ZIKV vaccine build on technologies that successfully reduced infection or disease burden against closely related flaviviruses or other RNA viruses. Subunit-based (DNA plasmid and modified mRNA), viral vectored (adeno- and measles viruses) and inactivated viral vaccines are already advancing to clinical trials in humans after successful mouse and non-human primate studies...
April 19, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28432455/dual-activation-of-toll-like-receptors-7-and-9-impairs-the-efficacy-of-antitumor-vaccines-in-murine-models-of-metastatic-breast-cancer
#3
Mariela A Moreno Ayala, María Florencia Gottardo, María Soledad Gori, Alejandro Javier Nicola Candia, Carla Caruso, Andrea De Laurentiis, Mercedes Imsen, Slobodanka Klein, Elisa Bal de Kier Joffé, Gabriela Salamone, Maria G Castro, Adriana Seilicovich, Marianela Candolfi
PURPOSE: Since combination of Toll-like receptor (TLR) ligands could boost antitumor immunity, we evaluated the efficacy of dendritic cell (DC) vaccines upon dual activation of TLR9 and TLR7 in breast cancer models. METHODS: DCs were generated from mouse bone marrow or peripheral blood from healthy human donors and stimulated with CpG1826 (mouse TLR9 agonist), CpG2006 or IMT504 (human TLR9 agonists) and R848 (TLR7 agonist). Efficacy of antitumor vaccines was evaluated in BALB/c mice bearing metastatic mammary adenocarcinomas...
April 21, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28426973/non-linear-enhancement-of-mrna-delivery-efficiencies-by-influenza-a-derived-ns1-protein-engendering-host-gene-inhibition-property
#4
Kyle K L Phua, Yi Liu, Shun Hui Sim
Nucleic acid induced immunogenicity remains a significant impediment in biomedical therapeutics because the innate immune system is a complex network overlaid with functional redundancies. Herein we report that non-structural protein 1 (NS1), an immune evasion protein derived from influenza A virus, when co-delivered in mRNA format is a potent mRNA transfection enhancer without toxicity. Transfection enhancement is mediated by NS1's effector domain through inhibition of IRF3 and PKR, activators of early anti-viral responses as well as CPSF30, a non immunostimulating protein...
April 12, 2017: Biomaterials
https://www.readbyqxmd.com/read/28421832/experimental-induction-of-chicken-aa-amyloidosis-in-white-layer-chickens-by-inoculation-with-inactivated-vaccines
#5
Wazir Ahmad Habibi, Takuya Hirai, Mohammad Hakim Niazmand, Naoko Okumura, Ryoji Yamaguchi
We investigated the amyloidogenic potential of inactivated vaccines and the localized production of serum amyloid A (SAA) at the injection site in white layer chickens. Hens in the treated group were injected intramuscularly three times with high doses of inactivated oil-emulsion Salmonella Enteritidis vaccine and multivalent viral and bacterial inactivated oil-emulsion vaccines at two week intervals. Chickens in the control group did not receive any inoculum. In the treated group, emaciation, and granulomas were present, while several chickens died between 4-6 weeks after the first injection...
April 19, 2017: Avian Pathology: Journal of the W.V.P.A
https://www.readbyqxmd.com/read/28421187/subset-specific-expression-of-toll-like-receptors-by-bovine-afferent-lymph-dendritic-cells
#6
Dirk Werling, Jayne C Hope, Nazneen Siddiqui, Stephanie Widdison, Chris Russell, Paul Sopp, Tracey J Coffey
Within the ruminant system, several possibilities exist to generate dendritic cells migrating out from the tissue into the regional draining lymph nodes as afferent lymph dendritic cells (ALDCs). Here, we analyzed toll-like receptor (TLR) 1-10 mRNA expression by using quantitative real-time PCR in highly purified subsets of bovine ALDC. As TLR expression may be influenced by pathogens or vaccines and their adjuvant, it is necessary to understand what TLRs are expressed in a steady-state system to elucidate specific differences and to potentially optimize targeted vaccines...
2017: Frontiers in Veterinary Science
https://www.readbyqxmd.com/read/28416600/induction-of-an-ifn-mediated-antiviral-response-by-a-self-amplifying-rna-vaccine-implications-for-vaccine-design
#7
Timothy Pepini, Anne-Marie Pulichino, Thomas Carsillo, Alicia L Carlson, Farid Sari-Sarraf, Katrin Ramsauer, Jason C Debasitis, Giulietta Maruggi, Gillis R Otten, Andrew J Geall, Dong Yu, Jeffrey B Ulmer, Carlo Iavarone
RNA-based vaccines have recently emerged as a promising alternative to the use of DNA-based and viral vector vaccines, in part because of the potential to simplify how vaccines are made and facilitate a rapid response to newly emerging infections. SAM vaccines are based on engineered self-amplifying mRNA (SAM) replicons encoding an Ag, and formulated with a synthetic delivery system, and they induce broad-based immune responses in preclinical animal models. In our study, in vivo imaging shows that after the immunization, SAM Ag expression has an initial gradual increase...
April 17, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28412170/lipid-nanoparticle-systems-for-enabling-gene-therapies
#8
REVIEW
Pieter R Cullis, Michael J Hope
Genetic drugs such as small interfering RNA (siRNA), mRNA, or plasmid DNA provide potential gene therapies to treat most diseases by silencing pathological genes, expressing therapeutic proteins, or through gene-editing applications. In order for genetic drugs to be used clinically, however, sophisticated delivery systems are required. Lipid nanoparticle (LNP) systems are currently the lead non-viral delivery systems for enabling the clinical potential of genetic drugs. Application will be made to the Food and Drug Administration (FDA) in 2017 for approval of an LNP siRNA drug to treat transthyretin-induced amyloidosis, presently an untreatable disease...
April 13, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28411378/immune-responses-and-long-term-disease-recurrence-status-after-telomerase-based-dendritic-cell-immunotherapy-in-patients-with-acute-myeloid-leukemia
#9
Hanna J Khoury, Robert H Collins, William Blum, Patrick S Stiff, Laurence Elias, Jane S Lebkowski, Anita Reddy, Kevin P Nishimoto, Debasish Sen, Edward D Wirth, Casey C Case, John F DiPersio
BACKGROUND: Telomerase activity in leukemic blasts frequently is increased among patients with high-risk acute myeloid leukemia (AML). In the current study, the authors evaluated the feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)-expressing autologous dendritic cells (hTERT-DCs) in adult patients with AML. METHODS: hTERT-DCs were produced from patient-specific leukapheresis, electroporated with an mRNA-encoding hTERT and a lysosomal-targeting sequence, and cryopreserved...
April 14, 2017: Cancer
https://www.readbyqxmd.com/read/28411277/long-term-survival-in-glioblastoma-with-cytomegalovirus-pp65-targeted-vaccination
#10
Kristen A Batich, Elizabeth A Reap, Gary E Archer, Luis Sanchez-Perez, Smita K Nair, Robert J Schmittling, Pam Norberg, Weihua Xie, James E Herndon, Patrick Healy, Roger E McLendon, Allan H Friedman, Henry S Friedman, Darell Bigner, Gordana Vlahovic, Duane A Mitchell, John H Sampson
Purpose: Patients with glioblastoma have less than 15-month median survival despite surgical resection, high-dose radiation, and chemotherapy with temozolomide. We previously demonstrated that targeting cytomegalovirus pp65 using dendritic cells (DC) can extend survival and, in a separate study, that dose-intensified temozolomide (DI-TMZ) and adjuvant granulocyte macrophage colony-stimulating factor (GM-CSF) potentiate tumor-specific immune responses in patients with glioblastoma. Here, we evaluated pp65-specific cellular responses following DI-TMZ with pp65-DCs and determined the effects on long-term progression-free survival (PFS) and overall survival (OS)...
April 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28401358/mrna-cancer-vaccines-messages-that-prevail
#11
Christian Grunwitz, Lena M Kranz
During the last decade, mRNA became increasingly recognized as a versatile tool for the development of new innovative therapeutics. Especially for vaccine development, mRNA is of outstanding interest and numerous clinical trials have been initiated. Strikingly, all of these studies have proven that large-scale GMP production of mRNA is feasible and concordantly report a favorable safety profile of mRNA vaccines. Induction of T-cell immunity is a multi-faceted process comprising antigen acquisition, antigen processing and presentation, as well as immune stimulation...
March 31, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28400857/estimation-of-the-overall-burden-of-cancers-precancerous-lesions-and-genital-warts-attributable-to-9-valent-hpv-vaccine-types-in-women-and-men-in-europe
#12
Susanne Hartwig, Jean Lacau St Guily, Géraldine Dominiak-Felden, Laia Alemany, Silvia de Sanjosé
BACKGROUND: In addition to cervical cancer, human papillomavirus (HPV) is responsible for a significant proportion of cancers and precancerous lesions of the vulva, vagina, anus, penis, head and neck, as well as genital warts. We estimated the annual number of new cases of these diseases attributable to 9-valent HPV vaccine types in women and men in Europe. METHODS: The annual number of new cancers of the cervix, vulva, vagina, anus, penis, and selected head and neck sites in the population of the European Medicines Agency territory was estimated based on age-specific incidence rates extracted from Cancer Incidence in 5 Continents, Volume X and Eurostat population data for 2015...
2017: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/28397799/an-mrna-based-vaccine-strategy-against-zika
#13
Gary Wong, George F Gao
Infections with Zika virus are strongly associated with complications such as congenital microcephaly and can trigger Guillain-Barré syndrome in humans, highlighting the urgent need for a safe, efficacious vaccine as a preventative countermeasure. In a recent paper published in Cell, Richner et al. generated a lipid nanoparticle encapsulated modified mRNA vaccine encoding the prM and E genes from Zika virus, which showed protection and sterilizing immunity in immunocompetent mice.
April 11, 2017: Cell Research
https://www.readbyqxmd.com/read/28392787/bioconjugation-of-small-molecules-to-rna-impedes-its-recognition-by-toll-like-receptor-7
#14
Isabell Hellmuth, Isabel Freund, Janine Schlöder, Salifu Seidu-Larry, Kathrin Thüring, Kaouthar Slama, Jens Langhanki, Stefka Kaloyanova, Tatjana Eigenbrod, Matthias Krumb, Sandra Röhm, Kalina Peneva, Till Opatz, Helmut Jonuleit, Alexander H Dalpke, Mark Helm
A fundamental mechanism of the innate immune system is the recognition, via extra- and intracellular pattern-recognition receptors, of pathogen-associated molecular patterns. A prominent example is represented by foreign nucleic acids, triggering the activation of several signaling pathways. Among these, the endosomal toll-like receptor 7 (TLR7) is known to be activated by single-stranded RNA (ssRNA), which can be specifically influenced through elements of sequence structure and posttranscriptional modifications...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28390158/lithium-chloride-inhibits-early-stages-of-foot-and-mouth-disease-virus-fmdv-replication-in-vitro
#15
Fu-Rong Zhao, Yin-Li Xie, Ze-Zhong Liu, Jun-Jun Shao, Shi-Fang Li, Yong-Guang Zhang, Hui-Yun Chang
Foot-and-mouth disease virus (FMDV) causes an economically important and highly contagious disease of cloven-hoofed animals such as cattle, swine, and sheep. FMD vaccine is the traditional way to protect against the disease, which can greatly reduce its occurrence. However, the use of FMD vaccines to protect early infection is limited. Therefore, the alternative strategy of applying antiviral agents is required to control the spread of FMDV in outbreak situations. As previously reported, LiCl has obviously inhibition effects on a variety of viruses such as transmissible gastroenteritis virus (TGEV), infectious bronchitis coronavirus (IBV), and pseudorabies herpesvirus and EV-A71 virus...
April 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28382943/badger-macrophages-fail-to-produce-nitric-oxide-a-key-anti-mycobacterial-effector-molecule
#16
Kirstin Bilham, Amy C Boyd, Stephen G Preston, Christina D Buesching, Chris Newman, David W Macdonald, Adrian L Smith
The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28378247/il-17a-plays-an-important-role-in-protection-induced-by-vaccination-with-fibronectin-binding-domain-of-fibronectin-binding-protein-a-against-staphylococcus-aureus-infection
#17
Kouji Narita, Krisana Asano, Akio Nakane
Fibronectin-binding protein A (FnBPA) of Staphylococcus aureus is a microbial surface component recognizing adhesive matrix molecules and has been known as one of the most important virulence factors involved in the initiation step of S. aureus infection. Therefore, it has been considered as a potential vaccine candidate. Previous studies have reported that vaccination with FnBPA protects animals against S. aureus infection. In this study, we demonstrated that vaccination with fibronectin-binding domain of FnBPA (FnBPA541-870) protects wild-type mice but not interleukin-17A (IL-17A)-deficient mice against S...
April 4, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28364024/angiotensin-ii-peptide-vaccine-protects-ischemic-brain-through-reducing-oxidative-stress
#18
Kouji Wakayama, Munehisa Shimamura, Jun-Ichi Suzuki, Ryo Watanabe, Hiroshi Koriyama, Hiroshi Akazawa, Hironori Nakagami, Hideki Mochizuki, Mitsuaki Isobe, Ryuichi Morishita
BACKGROUND AND PURPOSE: Medication nonadherence is one of major risk factors for the poor outcome in ischemic stroke. Vaccination is expected to solve such a problem because of its long-lasting effects, but its effect on ischemic brain damage is still unknown. Here, we focused on vaccination for renin-angiotensin system and examined the effects of angiotensin II (Ang II) peptide vaccine in permanent middle cerebral artery occlusion model in rats. METHODS: Male Wistar rats were exposed to permanent middle cerebral artery occlusion after 3× injections of Ang II peptide vaccine, and the serum or brain level of anti-Ang II antibody was examined...
March 31, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28359618/adjuvanticity-of-a-ctla-4-3-utr-complementary-oligonucleotide-for-emulsion-formulated-recombinant-subunit-and-inactivated-vaccines
#19
Xin Li, Lei Yang, Peiyan Zhao, Yun Yao, Fangjie Lu, Liqun Tu, Jiwei Liu, Zhiqin Li, Yongli Yu, Liying Wang
Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is recognized as a critical inhibitory regulator of T-cell proliferation and activation, opposing the action of CD28-mediated co-stimulation. Interfering or blocking CTLA-4 can result in continuous T-cell activation required for the full immune response to pathogenic microbes and vaccines. To test if nucleic acid-based CTLA-4 inhibitors could be developed into a novel adjuvant, we designed two oligonucleotides, CMD-1 and CMD-2, with the sequences complementary to the conserve regions identical between human and mouse CTLA-4 mRNA 3' untranslated region (3' UTR), and tested their in vitro effects on CTLA-4 production and their adjuvanticity for vaccines in mice...
March 27, 2017: Vaccine
https://www.readbyqxmd.com/read/28340344/modified-mrna-vaccines-protect-against-zika-virus-infection
#20
Justin M Richner, Sunny Himansu, Kimberly A Dowd, Scott L Butler, Vanessa Salazar, Julie M Fox, Justin G Julander, William W Tang, Sujan Shresta, Theodore C Pierson, Giuseppe Ciaramella, Michael S Diamond
No abstract text is available yet for this article.
March 23, 2017: Cell
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