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mRNA vaccine

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https://www.readbyqxmd.com/read/28802400/mycobacterium-tuberculosis-myma-is-a-tlr2-agonist-that-activate-macrophages-and-a-th1-response
#1
Iti Saraav, Swati Singh, Kirti Pandey, Monika Sharma, Sadhna Sharma
Cell wall of Mycobacterium tuberculosis (M.tb) is a major source of immunogenic proteins that can be tested as vaccine candidates. MymA (Rv3083), a 55 kDa M.tb flavin containing monooxygenase, is involved in modification of mycolic acids during acidic shock following M.tb internalization in macrophage. In this study, we have investigated the role of this cell wall associated protein in activation of macrophages by toll like receptor (TLRs) engagement and subsequent signaling. Our results showed that MymA stimulation of THP1 cells and human monocyte derived macrophages (MDM) lead to upregulation of TLR2 and co-stimulatory molecules CD40, CD80, CD86 and HLA-DR...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28794134/mrna-mediates-passive-vaccination-against-infectious-agents-toxins-and-tumors
#2
Moritz Thran, Jean Mukherjee, Marion Pönisch, Katja Fiedler, Andreas Thess, Barbara L Mui, Michael J Hope, Ying K Tam, Nigel Horscroft, Regina Heidenreich, Mariola Fotin-Mleczek, Charles B Shoemaker, Thomas Schlake
The delivery of genetic information has emerged as a valid therapeutic approach. Various reports have demonstrated that mRNA, besides its remarkable potential as vaccine, can also promote expression without inducing an adverse immune response against the encoded protein. In the current study, we set out to explore whether our technology based on chemically unmodified mRNA is suitable for passive immunization. To this end, various antibodies using different designs were expressed and characterized in vitro and in vivo in the fields of viral infections, toxin exposure, and cancer immunotherapies...
August 9, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28780099/effect-of-recombinant-bovine-somatotropin-on-leukocyte-mrna-expression-for-genes-related-to-cell-energy-metabolism-cytokine-production-phagocytosis-oxidative-burst-and-adaptive-immunity
#3
P R B Silva, C D Nelson, J P Driver, W W Thatcher, R C Chebel
Objectives of the current experiment were to evaluate the effects of treatment of periparturient dairy cows with recombinant bovine somatotropin (rbST) on mRNA expression in peripheral leukocytes for genes related to the somatotropic axis, cell energy metabolism, and innate and adaptive immune responses. Cows were enrolled in the experiment at 253 ± 3 d of gestation and assigned to an untreated control group (n = 98) or to receive 125 mg of rbST weekly from -21 to 21 d relative to calving (rbST125; n = 98)...
August 2, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28758019/current-trends-in-zika-vaccine-development
#4
EDITORIAL
Francisco A Lagunas-Rangel, Martha E Viveros-Sandoval, Arturo Reyes-Sandoval
The Zika virus (ZIKV) was first isolated in 1947 in Uganda. While it took 60 years for this virus to cause major outbreaks, an important shift in its ability to cause epidemics took place in the first and second decades of the this century: in 2007 in Yap Island, Micronesia, followed by French Polynesia in 2013 and, finally in 2015 and 2016, when ZIKV infections occurred throughout South America, Central America and the Caribbean, spreading rapidly to reach North America in just a single year. No licensed prophylactic vaccine is yet available but recent efforts towards the development of a vaccine have been remarkable from both the private and public sectors and include new candidate vaccines ranging from the classical live-attenuated or inactivated vaccines to more sophisticated approaches such as mRNA or genetically engineered viral platforms...
July 1, 2017: Journal of Virus Eradication
https://www.readbyqxmd.com/read/28754494/safety-and-immunogenicity-of-a-mrna-rabies-vaccine-in-healthy-adults-an-open-label-non-randomised-prospective-first-in-human-phase-1-clinical-trial
#5
Martin Alberer, Ulrike Gnad-Vogt, Henoch Sangjoon Hong, Keyvan Tadjalli Mehr, Linus Backert, Greg Finak, Raphael Gottardo, Mihai Alexandru Bica, Aurelio Garofano, Sven Dominik Koch, Mariola Fotin-Mleczek, Ingmar Hoerr, Ralf Clemens, Frank von Sonnenburg
BACKGROUND: Vaccines based on mRNA coding for antigens have been shown to be safe and immunogenic in preclinical models. We aimed to report results of the first-in-human proof-of-concept clinical trial in healthy adults of a prophylactic mRNA-based vaccine encoding rabies virus glycoprotein (CV7201). METHODS: We did an open-label, uncontrolled, prospective, phase 1 clinical trial at one centre in Munich, Germany. Healthy male and female volunteers (aged 18-40 years) with no history of rabies vaccination were sequentially enrolled...
July 25, 2017: Lancet
https://www.readbyqxmd.com/read/28750771/spatio-temporal-expression-of-mesocestoides-corti-mcval2-during-strobilar-development
#6
Alicia Costábile, Mónica Marín, Estela Castillo
VAL proteins belong to a diverse superfamily containing the CAP domain, with members described for various eukaryotic organisms, including parasites. They are implicated in diverse biological activities and, as secreted proteins, may be related in host - parasite interactions. For this reason they have been proposed as vaccine candidates against nematode infections. However, little is known about their function in cestodes. In M. corti, four partial cDNA sequences coding for members of the CAP superfamily were previously isolated...
July 24, 2017: Experimental Parasitology
https://www.readbyqxmd.com/read/28717398/preclinical-evaluation-of-nf-%C3%AE%C2%BAb-triggered-dendritic-cells-expressing-the-viral-oncogenic-driver-of-merkel-cell-carcinoma-for-therapeutic-vaccination
#7
Kerstin F Gerer, Michael Erdmann, Sine R Hadrup, Rikke Lyngaa, Lena-Marie Martin, Reinhard E Voll, Beatrice Schuler-Thurner, Gerold Schuler, Niels Schaft, Stefanie Hoyer, Jan Dörrie
BACKGROUND: Merkel cell carcinoma (MCC) is a rare but very aggressive skin tumor that develops after integration of a truncated form of the large T-antigen (truncLT) of the Merkel cell polyomavirus (MCV) into the host's genome. Therapeutic vaccination with dendritic cells (DCs) loaded with tumor antigens is an active form of immunotherapy, which intends to direct the immune system towards tumors which express the respective vaccination antigens. METHODS: Cytokine-matured monocyte-derived DCs of healthy donors and MCC patients were electroporated with mRNA encoding the truncLT...
July 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28713164/human-immunodeficiency-virus-type-1-induces-a-regulatory-b-cell-like-phenotype-in-vitro
#8
Jacobo Lopez-Abente, Adrián Prieto-Sanchez, Maria-Ángeles Muñoz-Fernandez, Rafael Correa-Rocha, Marjorie Pion
Individuals infected with human immunodeficiency virus type-1 (HIV-1) usually show a general dysregulation and hyper-activation of the immune system. A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described. However, the consequences of B-cell dysregulation are still poorly understood. We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli. The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+ and CD8+ T cells...
July 17, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28708997/vaccine-mediated-protection-against-zika-virus-induced-congenital-disease
#9
Justin M Richner, Brett W Jagger, Chao Shan, Camila R Fontes, Kimberly A Dowd, Bin Cao, Sunny Himansu, Elizabeth A Caine, Bruno T D Nunes, Daniele B A Medeiros, Antonio E Muruato, Bryant M Foreman, Huanle Luo, Tian Wang, Alan D Barrett, Scott C Weaver, Pedro F C Vasconcelos, Shannan L Rossi, Giuseppe Ciaramella, Indira U Mysorekar, Theodore C Pierson, Pei-Yong Shi, Michael S Diamond
The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28701399/selective-expression-of-ccr10-and-cxcr3-by-circulating-human-hsv-specific-cd8-t-cells
#10
Michael T Hensel, Tao Peng, Anqi Cheng, Stephen C De Rosa, Anna Wald, Kerry J Laing, Lichen Jing, Lichun Dong, Amalia S Magaret, David M Koelle
Herpes simplex virus type (HSV) infection is restricted to epithelial cells and neurons and is controlled by CD8 T-cells. These cells both traffic to epithelial sites of recurrent lytic infection and to ganglia, and persist at the dermal-epidermal junction for up to 12 weeks after lesion resolution. We previously showed that cutaneous lymphocyte-associated antigen (CLA), a functional E-selectin ligand (ESL), is selectively expressed on circulating HSV-2-specific CD8 T-cells. CLA/ESL mediates adhesion of T-cells to inflamed vascular endothelium...
July 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28701102/mechanism-of-action-of-mrna-based-vaccines
#11
Carlo Iavarone, Derek T O'hagan, Dong Yu, Nicolas F Delahaye, Jeffrey B Ulmer
The present review summarizes the growing body of work defining the mechanisms of action of this exciting new vaccine technology that should allow rational approaches in the design of next generation mRNA vaccines. Areas covered: Bio-distribution of mRNA, localization of antigen production, role of the innate immunity, priming of the adaptive immune response, route of administration and effects of mRNA delivery systems. Expert commentary: In the last few years, the development of RNA vaccines had a fast growth, the rising number of proof will enable rational approaches to improving the effectiveness and safety of this modern class of medicine...
September 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28698120/effectiveness-of-formalin-killed-vaccines-containing-cpg-oligodeoxynucleotide-1668-adjuvants-against-vibrio-harveyi-in-orange-spotted-grouper
#12
Hai Trong Nguyen, Thuy Thi Thu Nguyen, Yi-Ting Wang, Pei-Chyi Wang, Shih-Chu Chen
Vibrio harveyi is a major bacterial pathogen that causes serious vibriosis in cultured groupers, leading to massive deaths. In this study, we evaluated the immune responses and protective efficacy of vaccines containing V. harveyi formalin-killed cells (FKC) formulated with CpG ODN 1668-enriched plasmids (p30CpG and p60CpG) in the orange-spotted grouper. Results indicated that antibody titres were remarkably increased in vaccinated fish 2 weeks post-immunisation. Expression level of major histocompatibility complex (MHC) class II, CD 8, and toll-like receptor 9 was significantly upregulated in the spleen of fish immunised with CpG ODN 1668-adjuvanted vaccines, as recorded at 6 weeks after immunisation...
July 8, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28694808/mycobacterium-tuberculosis-dosr-regulon-gene-rv2004c-encodes-a-novel-antigen-with-pro-inflammatory-functions-and-potential-diagnostic-application-for-detection-of-latent-tuberculosis
#13
Sankara Narayana Doddam, Vidyullatha Peddireddy, Niyaz Ahmed
Approximately 1.7 billion people in the world harbor latent Mycobacterium tuberculosis (Mtb) with a substantial risk of progression to clinical outcome. Containment of these seed beds of Mtb is essential to eliminate tuberculosis completely in high burden settings such as India. Hence, there is an urgent need for the identification of new serological markers for detection or vaccine candidates to prevent latent tuberculosis infection (LTBI). DosR regulon antigens of Mtb might serve as attractive targets for LTBI diagnosis or vaccine development as they are specifically expressed and are upregulated during latent phase...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28693166/quantitative-analysis-and-clonal-characterization-of-t-cell-receptor-%C3%AE-repertoires-in-patients-with-advanced-non-small-cell-lung-cancer-treated-with-cancer-vaccine
#14
Tu Mai, Atsushi Takano, Hiroyuki Suzuki, Takashi Hirose, Takahiro Mori, Koji Teramoto, Kazuma Kiyotani, Yusuke Nakamura, Yataro Daigo
With the development of cancer immunotherapy that may activate T cells, a practical and quantitative method to improve monitoring and/or prediction of immunological response of patients as a predictive biomarker is of importance. To examine possible biomarkers for a therapeutic cancer vaccine containing a mixture of three epitope peptides derived from cell division-associated 1, lymphocyte antigen 6 complex locus K and insulin-like growth factor-II mRNA-binding protein 3, T-cell receptor β (TCRβ) repertoires of blood samples from 24 patients with human leukocyte antigen-A*2402-positive non-small cell lung cancer were characterized prior to and following 8 weeks of the cancer vaccine treatment, by applying a next-generation sequencing method...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28691653/molecular-biochemical-characterization-and-assessment-of-immunogenic-potential-of-cofactor-independent-phosphoglycerate-mutase-against-leishmania-donovani-a-step-towards-exploring-novel-vaccine-candidate
#15
Rati Tandon, Sharat Chandra, Rajendra Kumar Baharia, Pragya Misra, Sanchita DAS, Keerti Rawat, Mohammad Imran Siddiqi, Shyam Sundar, Anuradha Dube
Despite immense efforts, vaccine against visceral leishmaniasis has yet not been developed. Earlier our proteomic study revealed a novel protein, cofactor-independent phoshoglycerate mutase (LdiPGAM), an important enzyme in glucose metabolism, in T helper cells type 1 (Th1) stimulatory region of soluble Leishmania donovani antigen. In this study, LdiPGAM was biochemically and molecularly characterized and evaluated for its immunogenicity and prophylactic efficacy against L. donovani. Immunogenicity of recombinant LdiPGAM (rLdiPGAM) was initially assessed in naïve hamsters immunized with it by analysing mRNA expression of inducible nitric oxide (NO) synthase (iNOS) and other Th1/T helper cells type 2 cytokines, which revealed an upregulation of Th1 cytokines along with iNOS...
July 10, 2017: Parasitology
https://www.readbyqxmd.com/read/28675247/protection-by-humoral-elements-independent-of-virus-neutralization-activity-against-an-influenza-virus-challenge
#16
Julia Sarkadi, David Kuti, Mate Jankovics, Eva Pallinger, Kinga Fodor, Zoltan Kis, Eva Gonczol, Ildiko Visontai, Istvan Jankovics
To investigate the protective efficacy of a seasonal trivalent inactivated whole virion influenza vaccine (TIV) adjuvanted with aluminum phosphate (Fluval AB, referred to here as TIV+Al), we immunized mice with the TIV+Al, and as controls, with TIV, TIV+Al combined with Freund adjuvant (TIV+Al+F), inactivated A/PR/8/34(H1N1) (PR8) strain or PBS, and challenged them with a lethal dose of a mouse-adapted PR8 virus. Serum pools from immunized mice were passively transferred to recipient mice that were then challenged similarly...
July 4, 2017: New Microbiologica
https://www.readbyqxmd.com/read/28670908/effects-of-lactobacillus-rhamnosus-gg-on-the-maturation-and-differentiation-of-dendritic-cells-in-rotavirus-infected-mice
#17
Y Jiang, L Ye, Y Cui, G Yang, W Yang, J Wang, J Hu, W Gu, C Shi, H Huang, C Wang
Rotavirus-related diarrhoea is considered one of the most important diseases in field animal production. In addition to the classic vaccine strategy, a number of studies have utilised probiotics, such as Lactobacillus rhamnosus GG (LGG), to prevent rotavirus-induced diarrhoea. Although it has been partially revealed that Toll-like receptors (TLRs) are involved in the LGG-mediated protection against rotavirus infection, the details of the underlying immunologic mechanisms remain largely unknown. In this study, three-to-four-week-old female BALB/c mice were divided into three groups and orally administered phosphate buffered saline (PBS), PBS plus rotavirus or LGG plus rotavirus, respectively...
July 3, 2017: Beneficial Microbes
https://www.readbyqxmd.com/read/28668567/10-valent-pneumococcal-conjugate-vaccine-pcv10-decreases-metabolic-activity-but-not-nasopharyngeal-carriage-of-streptococcus-pneumoniae-and-haemophilus-influenzae
#18
Dafne C Andrade, Igor C Borges, Maiara L Bouzas, Juliana R Oliveira, Kiyoshi F Fukutani, Artur T Queiroz, Camila Indiani de Oliveira, Aldina Barral, Johan Van Weyenbergh, Cristiana Nascimento-Carvalho
BACKGROUND: The effect of pneumococcal vaccination is widely variable when measured by nasopharyngeal carriage of vaccine and non-vaccine targets. The aim of this study was to compare the carriage rates and metabolic activity of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis among children who were or were not vaccinated with PCV10. METHODS: We included children with acute respiratory infection aged 6-23months from a cross-sectional study (CHIADO-IVAS)...
June 28, 2017: Vaccine
https://www.readbyqxmd.com/read/28648976/synergistic-combination-of-murine-bone-marrow-derived-dendritic-cells-loaded-ex-vivo-with-whole-tumor-lysate-and-systemic-chemotherapy-mediates-antitumor-immune-responses-in-vivo
#19
Mohamed L Salem, Mohamed Nassef, Soha Gomaa, Ibrahim Essa
In order to get mature dendritic cells (DC) that is a crucial prerequisite for success in tumor immunotherapy protocols. Herein, we assumed that administration of murine bone marrow (BM)-derived DC (BM-DC), loaded ex vivo with whole Ehrlich ascites carcinoma (EAC) lysate, in the context of systemic chemotherapy cyclophosphamide (CTX) to induce antitumor immune responses, may be a good strategy to improve the presentation of tumor-specific antigens to the immune system. In the first series of experiments, BM cells generated either from BM of naïve mice or from BM of EAC-bearing mice were cultured in the presence of GM-CSF and IL-4 for 6days...
September 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28648870/tlr7-and-tlr8-agonist-resiquimod-r848-differently-regulates-mif-expression-in-cells-and-organs
#20
Yao Mawulikplimi Adzavon, Pengxiang Zhao, Baobei Lv, Mengyu Liu, Xin Zhang, Fei Xie, Linqi Yang, Lei Shang, Mingzi Zhang, Qinjian Li, Xuemei Ma
Since its first description in 1966, macrophage migration inhibitory factor (MIF) was found to play a critical role in inflammatory and immune responses as well as in disease pathogenesis especially in tumor pathogenesis and cancer progression. MIF is expressed in different cell types and is associated with many disease severity and tumor pathogenesis. Here, we investigated the influence of TLR7 and TLR8 agonist resiquimod (R848), an immune response inducer used as a prophylactic agent for several infectious diseases as well as anticancer agents and vaccine adjuvant on MIF expression in cells and organs...
June 22, 2017: Cytokine
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