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mRNA vaccine

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https://www.readbyqxmd.com/read/29456015/multi-antigenic-human-cytomegalovirus-mrna-vaccines-that-elicit-potent-humoral-and-cell-mediated-immunity
#1
Shinu John, Olga Yuzhakov, Angela Woods, Jessica Deterling, Kimberly Hassett, Christine A Shaw, Giuseppe Ciaramella
A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neutralizing antibodies and antigen-specific T cells have been implicated in controlling infection. We demonstrate that the immunization of mice and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit potent and durable neutralizing antibody titers...
February 14, 2018: Vaccine
https://www.readbyqxmd.com/read/29448955/analysis-of-the-genetic-diversity-and-mrna-expression-level-in-porcine-reproductive-and-respiratory-syndrome-virus-vaccinated-pigs-that-developed-short-or-long-viremias-after-challenge
#2
Martí Cortey, Gaston Arocena, Tahar Ait-Ali, Anna Vidal, Yanli Li, Gerard Martín-Valls, Alison D Wilson, Allan L Archibald, Enric Mateu, Laila Darwich
Porcine reproductive and respiratory syndrome virus (PRRSv) infection alters the host's cellular and humoral immune response. Immunity against PRRSv is multigenic and vary between individuals. The aim of the present study was to compare several genes that encode for molecules involved in the immune response between two groups of vaccinated pigs that experienced short or long viremic periods after PRRSv challenge. These analyses include the sequencing of four SLA Class I, two Class II allele groups, and CD163, plus the analysis by quantitative realtime qRT-PCR of the constitutive expression of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 mRNA and other molecules in peripheral blood mononuclear cells...
February 15, 2018: Veterinary Research
https://www.readbyqxmd.com/read/29442228/effect-of-an-88-amino-acid-deletion-in-nsp2-of-porcine-reproductive-and-respiratory-syndrome-virus-on-virus-replication-and-cytokine-responses-in-vitro
#3
Wei He, Ying Wei, Jing Yao, Xin Xie, Jiabin Huang, Siyuan Lin, Kang Ouyang, Ying Chen, Weijian Huang, Zuzhang Wei
Previously, a spontaneous 88-amino-acid (aa) deletion in nsp2 was associated with cell-adaptation of porcine reproductive and respiratory syndrome virus (PRRSV) strain JXM100, which arose during passaging of the highly pathogenic PRRSV (HP-PRRSV) strain JX143 in MARC-145 cells. Here, to elucidate the biological role of this deletion, we specifically deleted the region of a cDNA clone of HP-PRRSV strain JX143 (pJX143) corresponding to these 88 amino acids. The effect of the deletion on virus replication in cultured cells and transcriptional activation of inflammatory cytokines and chemokines in pulmonary alveolar macrophages (PAMs) was examined...
February 13, 2018: Archives of Virology
https://www.readbyqxmd.com/read/29437538/leveraging-rational-protein-engineering-to-improve-mrna-therapeutics
#4
Jeremiah D Farelli, Kirtika H Asrani, Cleo Isaacs, Joanna S deBear, Mary R Stahley, Anumeha Shah, Melissa A Lasaro, Christopher J Cheng, Romesh R Subramanian
Messenger RNA (mRNA) is a promising new class of therapeutics that has potential for treatment of diseases in fields such as immunology, oncology, vaccines, and inborn errors of metabolism. mRNA therapy has several advantages over DNA-based gene therapy, including the lack of the need for nuclear import and transcription, as well as limited possibility of genomic integration. One drawback of mRNA therapy, especially in cases such as metabolic disorders where repeated dosing will be necessary, is the relatively short in vivo half-life of mRNA (∼6-12 h)...
February 13, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29434590/killed-whole-cell-oral-cholera-vaccine-induces-ccl20-secretion-by-human-intestinal-epithelial-cells-in-the-presence-of-the-short-chain-fatty-acid-butyrate
#5
Ju-Ri Sim, Seok-Seong Kang, Daesang Lee, Cheol-Heui Yun, Seung Hyun Han
Short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate, modulate immune responses in the gut. However, the effect of SCFAs on mucosal vaccine-induced immune cell migration is poorly understood. Here, we investigated whether SCFAs modulate chemokine expression induced by the killed whole-cell oral cholera vaccine, Shanchol™, in human intestinal epithelial cells. Shanchol™ induced expression of CCL2, CCL5, CCL20, and CXCL10 at the mRNA level, but not at the protein level. Interestingly, CCL20 secretion was substantially increased by co-stimulation with Shanchol™ and butyrate, while neither acetate nor propionate showed such effect...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29432451/microexon-gene-transcriptional-profiles-and-evolution-provide-insights-into-blood-processing-by-the-schistosoma-japonicum-esophagus
#6
Xiao-Hong Li, Ricardo DeMarco, Leandro X Neves, Sally R James, Katherine Newling, Peter D Ashton, Jian-Ping Cao, R Alan Wilson, William Castro-Borges
BACKGROUND: Adult schistosomes have a well-developed alimentary tract comprising an oral sucker around the mouth, a short esophagus and a blind ending gut. The esophagus is not simply a muscular tube for conducting blood from the mouth to gut but is divided into compartments, surrounded by anterior and posterior glands, where processing of ingested blood is initiated. Self-cure of rhesus macaques from a Schistosoma japonicum infection appears to operate by blocking the secretory functions of these glands so that the worms cease feeding and slowly starve to death...
February 12, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29426344/implementation-strategies-to-improve-cervical-cancer-prevention-in-sub-saharan-africa-a-systematic-review
#7
REVIEW
Lauren G Johnson, Allison Armstrong, Caroline M Joyce, Anne M Teitelman, Alison M Buttenheim
BACKGROUND: Developed countries, such as the USA, have achieved significant decreases in cervical cancer burden since the introduction of Pap smear-based programs in the 1960s. Due to implementation barriers and limited resources, many countries in sub-Saharan Africa (SSA) have been unable to attain such reductions. The purpose of this review is to evaluate implementation strategies used to improve the uptake and sustainability of cervical cancer prevention programs in SSA. METHODS: A reviewer (LJ) independently searched PubMed, Ovid/MEDLINE, Scopus, and Web of Science databases for relevant articles with the following search limits: English language, peer reviewed, and published between 1996 and 2017...
February 9, 2018: Implementation Science: IS
https://www.readbyqxmd.com/read/29423380/firewalls-prevent-systemic-dissemination-of-vectors-derived-from-human-adenovirus-type-5-and-suppress-production-of-transgene-encoded-antigen-in-a-murine-model-of-oral-vaccination
#8
Julien Revaud, Yves Unterfinger, Nicolas Rol, Muhammad Suleman, Julia Shaw, Sandra Galea, Françoise Gavard, Sandrine A Lacour, Muriel Coulpier, Nicolas Versillé, Menzo Havenga, Bernard Klonjkowski, Gina Zanella, Stéphane Biacchesi, Nathalie Cordonnier, Blaise Corthésy, Juliette Ben Arous, Jennifer P Richardson
To define the bottlenecks that restrict antigen expression after oral administration of viral-vectored vaccines, we tracked vectors derived from the human adenovirus type 5 at whole body, tissue, and cellular scales throughout the digestive tract in a murine model of oral delivery. After intragastric administration of vectors encoding firefly luciferase or a model antigen, detectable levels of transgene-encoded protein or mRNA were confined to the intestine, and restricted to delimited anatomical zones. Expression of luciferase in the form of multiple small bioluminescent foci in the distal ileum, cecum, and proximal colon suggested multiple crossing points...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29416539/adjuvant-effect-of-bacille-calmette-gu%C3%A3-rin-on-hepatitis-b-vaccine-immunogenicity-in-the-preterm-and-term-newborn
#9
Annette Scheid, Francesco Borriello, Carlo Pietrasanta, Helen Christou, Joann Diray-Arce, Matthew A Pettengill, Sweta Joshi, Ning Li, Ilana Bergelson, Tobias Kollmann, David J Dowling, Ofer Levy
Immunization is key to protecting term and preterm infants from a heightened risk of infection. However, preterm immunity is distinct from that of the term, limiting its ability to effectively respond to vaccines routinely given at birth, such as hepatitis B vaccine (HBV). As part of the Expanded Program on Immunization, HBV is often given together with the live-attenuated vaccine Bacille Calmette-Guérin (BCG), known to activate multiple pattern-recognition receptors. Of note, some clinical studies suggest BCG can enhance efficacy of other vaccines in term newborns...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29408645/novel-subunit-vaccine-based-on-grass-carp-reovirus-vp35-protein-provides-protective-immunity-against-grass-carp-hemorrhagic-disease
#10
Yan Gao, Chao Pei, Xiaoying Sun, Chao Zhang, Li Li, Xianghui Kong
The grass carp (Ctenopharyngodon idella) hemorrhagic disease, caused by grass carp reovirus (GCRV), is one of the most severe infectious diseases in aquaculture. Given that antiviral therapies are currently limitedly available, vaccination remains the most effective means for the prevention of viral diseases, such as GCRV. A reovirus strain, which was temporarily named GCRV-HN14, was recently isolated from grass carp in Henan province, China. The S11 gene fragment of GCRV-HN14 was speculated to encode viral structural protein VP35, which has no equivalent gene in other aquareviruses but has antigenic epitopes...
February 3, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29406242/live-recombinant-lactococcuslactis-expressing-avian-hepatitis-virus-orf2-protein-immunoprotection-against-homologous-virus-challenge-in-chickens
#11
Dian Wang, Yue Zhang, Chunli Ma, Dexing Ma, Qin Zhao, Fen Wang, Yuchen Huang, Jian Li, Lili Zhang, En-Min Zhou
Avian hepatitis E virus (aHEV) is a pathogen associated with hepatitis-splenomegaly syndrome in chickens. To date, no commercial vaccine is available for preventing aHEV infection. In this study, three recombinant LactococcuslactisNZ9000experimental live vaccines expressing cytoplasmic, secreted, and cell wall-anchored forms of aHEV truncated ORF2 protein spanning amino acids 249-606 (ΔORF2) were constructed using pTX8048 vector and characterized. Each chicken was immunized three times at two-week intervals with one of the three live aHEV ORF2 vaccines (experimental group) or with live vaccine containing empty vector only (control group)...
February 14, 2018: Vaccine
https://www.readbyqxmd.com/read/29399179/antitumor-and-immunostimulatory-activities-of-a-genotype-v-recombinant-attenuated-veterinary-newcastle-disease-virus-vaccine
#12
Oscar Antonio Ortega-Rivera, J Luis Quintanar, Susana Del Toro-Arreola, Ángel G Alpuche-Solis, Mayra J Esparza-Araiza, Eva Salinas
Antitumor conventional treatments including chemo/radiotherapy result in several side effects and non-specificity. Therapies including the use of oncolytic viruses, particularly the Newcastle disease virus (NDV), have emerged as an attractive alternative due to their capacity to kill cancer cells directly or through stimulation of the immune system. In the present study, a commercial vaccine composed of a recombinant attenuated NDV strain P05 (rNDV-P05) was assessed for antitumor and immunostimulatory activity...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29396196/disruption-of-blood-meal-responsive-serpins-prevents-ixodes-scapularis-from-feeding-to-repletion
#13
Mariam Bakshi, Tae Kwon Kim, Albert Mulenga
Serine protease inhibitors (serpins) are thought to mediate the tick's evasion of the host's serine protease-mediated defense pathways such as inflammation and blood clotting. This study describes characterization and target validation of 11 blood meal-responsive serpins that are associated with nymph and adult Ixodes scapularis tick feeding as revealed by quantitative (q)RT-PCR and RNAi silencing analyses. Given the high number of targets, we used combinatorial (co) RNAi silencing to disrupt candidate serpins in two groups (G): seven highly identical and four non-identical serpins based on amino acid identities, here after called GI and GII respectively...
January 10, 2018: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/29381969/hpv-types-in-cervical-cancer-tissue-in-south-africa-a-head-to-head-comparison-by-mrna-and-dna-tests
#14
Amir Rad, Sveinung Wergeland Sørbye, Greta Dreyer, Siri Hovland, Bente Marie Falang, Melanie Louw, Finn Egil Skjeldestad
Accurate identification of human papillomavirus (HPV)-types in cervical cancer tissue may be important for tailoring tests for primary screening and types to be included in a vaccine. The aim of this study was to compare test-performance of a 45-type HPV deoxyribonucleic acid (DNA)-test with a 9-type HPV messenger ribonucleic acid (mRNA)-test in cervical cancer tissues.In a case-series design 188 women with diagnosed cervical cancer during the period January 2008 to July 1, 2011 at the Gynaecological Oncology Unit, University of Pretoria, South Africa were recruited to the study...
November 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29381765/differential-mirna-expression-in-b-cells-is-associated-with-inter-individual-differences-in-humoral-immune-response-to-measles-vaccination
#15
Iana H Haralambieva, Richard B Kennedy, Whitney L Simon, Krista M Goergen, Diane E Grill, Inna G Ovsyannikova, Gregory A Poland
BACKGROUND: MicroRNAs are important mediators of post-transcriptional regulation of gene expression through RNA degradation and translational repression, and are emerging biomarkers of immune system activation/response after vaccination. METHODS: We performed Next Generation Sequencing (mRNA-Seq) of intracellular miRNAs in measles virus-stimulated B and CD4+ T cells from high and low antibody responders to measles vaccine. Negative binomial generalized estimating equation (GEE) models were used for miRNA assessment and the DIANA tool was used for gene/target prediction and pathway enrichment analysis...
2018: PloS One
https://www.readbyqxmd.com/read/29370775/case-report-mechanisms-of-hiv-elite-control-in-two-african-women
#16
Yumna Moosa, Ramla F Tanko, Veron Ramsuran, Ravesh Singh, Mashudu Madzivhandila, Nonhlanhla Yende-Zuma, Melissa-Rose Abrahams, Philippe Selhorst, Kamini Gounder, Penny L Moore, Carolyn Williamson, Salim S Abdool Karim, Nigel J Garrett, Wendy A Burgers
BACKGROUND: The majority of people living with HIV require antiretroviral therapy (ART) for controlling viral replication, however there are rare HIV controllers who spontaneously and durably control HIV in the absence of treatment. Understanding what mediates viral control in these individuals has provided us with insights into the immune mechanisms that may be important to induce for a vaccine or functional cure for HIV. To date, few African elite controllers from high incidence settings have been described...
January 25, 2018: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29359186/recombinant-zika-virus-subunits-are-immunogenic-and-efficacious-in-mice
#17
Albert To, Liana O Medina, Kenji O Mfuh, Michael M Lieberman, Teri Ann S Wong, Madhuri Namekar, Eileen Nakano, Chih-Yun Lai, Mukesh Kumar, Vivek R Nerurkar, Axel T Lehrer
Following the 2015 Zika virus (ZIKV) outbreaks in the South Pacific, Caribbean, and Americas, ZIKV has emerged as a serious threat due to its association with infantile microcephaly and other neurologic disorders. Despite an international effort to develop a safe and effective vaccine to combat congenital Zika syndrome and ZIKV infection, only DNA and mRNA vaccines encoding the precursor membrane (prM) and envelope (E) proteins, an inactivated-ZIKV vaccine, and a measles virus-based ZIKV vaccine are currently in phase I or II (prM/E DNA) clinical trials...
January 2018: MSphere
https://www.readbyqxmd.com/read/29355535/a-test-of-the-effects-of-androgens-on-immunity-no-relationship-between-11-ketotestosterone-and-immune-performance-in-bluegill-lepomis-macrochirus
#18
John W Loggie, Shawn R Garner, Charlyn G Partridge, Brian Dixon, Rosemary Knapp, Bryan D Neff
The immunosuppressive effects of androgens are a key component of the immunocompetence handicap hypothesis (ICHH). Here, we use bluegill sunfish (Lepomis macrochirus) to test two predictions arising from this hypothesis: (1) natural circulating concentrations of the androgen 11-ketotestosterone (11-KT) will be negatively related with measures of immunity, and (2) immune stimulation will lower circulating 11-KT concentration. We found no evidence for a relationship between natural circulating 11-KT concentration and measures of immunity (lymphocyte and granulocyte counts, respiratory burst, cytokine mRNA levels), and an immune stimulation with Vibrio vaccine did not affect circulating 11-KT concentration...
January 16, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/29335856/abscopal-effects-of-radiotherapy-and-combined-mrna-based-immunotherapy-in-a-syngeneic-ova-expressing-thymoma-mouse-model
#19
Lucas Basler, Aleksandra Kowalczyk, Regina Heidenreich, Mariola Fotin-Mleczek, Savas Tsitsekidis, Daniel Zips, Franziska Eckert, Stephan M Huber
BACKGROUND: Tumor metastasis and immune evasion present major challenges of cancer treatment. Radiotherapy can overcome immunosuppressive tumor microenvironments. Anecdotal reports suggest abscopal anti-tumor immune responses. This study assesses abscopal effects of radiotherapy in combination with mRNA-based cancer vaccination (RNActive®). METHODS: C57BL/6 mice were injected with ovalbumin-expressing thymoma cells into the right hind leg (primary tumor) and left flank (secondary tumor) with a delay of 4 days...
January 16, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29331806/unifying-in%C3%A2-vitro-and-in%C3%A2-vivo-ivt-mrna-expression-discrepancies-in-skeletal-muscle-via-mechanotransduction
#20
Sushma M Bhosle, Kristin H Loomis, Jonathan L Kirschman, Emmeline L Blanchard, Daryll A Vanover, Chiara Zurla, Damien Habrant, Darin Edwards, Patrick Baumhof, Bruno Pitard, Philip J Santangelo
The translational efficiency of an in vitro transcribed (IVT) mRNA was measured upon delivery to primary skeletal muscle cells and to a mouse model system, towards the development of a predictive in vitro assay for the screening and validation of intramuscular mRNA-based vaccines. When IVT mRNA was delivered either naked or complexed with novel aminoglycoside-based delivery vehicles, significant differences in protein expression in vitro and in vivo were observed. We hypothesized that this previously anticipated discrepancy was due to differences in the mechanism of IVT mRNA endosomal entry and release following delivery...
January 6, 2018: Biomaterials
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