Search results for: AntiAdenovirus
#31711794 2019/11/03 To Up
Optimization of piperazine-derived ureas privileged structures for effective antiadenovirus agents.In recent years, human adenovirus (HAdV) infections have shown a high clinical impact in both immunosuppressed and immunocompetent patients. The research into specific antiviral drugs for the treatment of HAdV infections in immunocompromised patients constitutes a principal objective for medicinal chemistry due to the lack of any specific secure drug to treat these infections. In this study, we report a small-molecule library (67 compounds) designed from an optimization process of piperazine-derived urea privileged structures and their biological evaluation: antiviral activity and cytotoxicity. The active compounds selected were further evaluated to gain mechanistic understanding for their inhibition. Twelve derivatives were identified that inhibited HAdV infections at nanomolar and low micromolar concentrations (IC from 0.6 to 5.1â¯Î¼M) with low cytotoxicity. In addition, our mechanistic assays suggested differences in the way the derivatives exert their anti-HAdV activity targeting transcription, DNA replication and later steps in the HAdV replication cycle. Furthermore, eight of the 12 studied derivatives blocked human cytomegalovirus (HCMV) DNA replication at low micromolar concentrations. The data provided herein indicates that the 12 thiourea/urea piperazine derivatives studied may represent potential lead compounds for clinical evaluation and development of new anti-HAdV drugs.
Sarah Mazzotta, JosÃ© Antonio Marrugal-Lorenzo, Margarita Vega-Holm, Ana Serna-Gallego, Jaime Ãlvarez-Vidal, Judith Berastegui-Cabrera, JosÃ© PÃ©rez Del Palacio, Caridad DÃaz, Francesca Aiello, JerÃ³nimo PachÃ³n, Fernando Iglesias-Guerra, JosÃ© Manuel Vega-PÃ©rez, Javier SÃ¡nchez-CÃ©spedes
2593 related Products with: Optimization of piperazine-derived ureas privileged structures for effective antiadenovirus agents.100 G1.00 flask250 mg0.1ml (1mg/ml) 100 G10 mg 1 G100 µg1 LITRE100 U
#27076643 2016/06/10 To Up
Diminished Innate Antiviral Response to Adenovirus Vectors in cGAS/STING-Deficient Mice Minimally Impacts Adaptive Immunity.Infection by adenovirus, a nonenveloped DNA virus, induces antiviral innate and adaptive immune responses. Studies of transformed human and murine cell lines using short hairpin RNA (shRNA) knockdown strategies identified cyclic guanine adenine synthase (cGAS) as a pattern recognition receptor (PRR) that contributes to the antiadenovirus response. Here we demonstrate how the cGAS/STING cascade influences the antiviral innate and adaptive immune responses in a murine knockout model. Using knockout bone marrow-derived dendritic cells (BMDCs) and bone marrow-derived macrophages (BMMOs), we determined that cGAS and STING are essential to the induction of the antiadenovirus response in these antigen-presenting cells (APCs) in vitro We next determined how the cGAS/STING cascade impacts the antiviral response following systemic administration of a recombinant adenovirus type 5 vector (rAd5V). Infection of cGAS(-/-) and STING(-/-) mice results in a compromised early antiviral innate response compared to that in wild-type (WT) controls: significantly lower levels of beta interferon (IFN-Î²) secretion, low levels of proinflammatory chemokine induction, and reduced levels of antiviral transcript induction in hepatic tissue. At 24 h postinfection, levels of viral DNA and reporter gene expression in the liver were similar in all strains. At 28 days postinfection, clearance of infected hepatocytes in cGAS or STING knockout mice was comparable to that in WT C57BL/6 mice. Levels of neutralizing anti-Ad5V antibody were modestly reduced in infected cGAS mice. These data support a dominant role for the cGAS/STING cascade in the early innate antiviral inflammatory response to adenovirus vectors. However, loss of the cGAS/STING pathway did not affect viral clearance, and cGAS deficiency had a modest influence on the magnitude of the antiviral humoral immune response to adenovirus infections.
Daniela Anghelina, Eric Lam, Erik Falck-Pedersen
2024 related Products with: Diminished Innate Antiviral Response to Adenovirus Vectors in cGAS/STING-Deficient Mice Minimally Impacts Adaptive Immunity.100 μg100 mg501 kit1 mg96 wells1025 100
#26996057 2016/03/29 To Up
Spectrally and Spatially Multiplexed Serological Array-in-Well Assay Utilizing Two-Color Upconversion Luminescence Imaging.We demonstrate a simple dual-mode multiplexed array-in-well immunoassay for simultaneous classification and detection of serum IgG and IgM antibodies against influenza A and human adenoviruses based on the color and position of the upconversion luminescence on the array. Biotinylated influenza A/H1N1 and A/H5N1 as well as adenovirus serotype 2 and 5 hexon antigens along with positive and negative controls were printed in an array format onto the bottom of streptavidin-coated microtiter wells. The anti-influenza A and antiadenovirus antibodies present in the sample were captured to the array and detected with antihuman antibody-coated upconverting nanophosphors (UCNPs). The green emitting UCNPs (NaYF4:Yb(3+),Er(3+)) coated with antihuman IgG and blue emitting UCNPs (NaYF4:Yb(3+),Tm(3+)) coated with antihuman IgM were used to detect human IgG and IgM antibodies, respectively. The emission of the bound UCNPs was imaged free of autofluorescence with anti-Stokes photoluminescence microwell imager. No spectral cross-talk was observed between green and blue emitting UCNPs. Also the cross-reactivities between UCNP-conjugates and immobilized human IgG and IgM antibodies were negligible. Position of the signal on the array defined the antigen specificity and the antibody class was defined by the color of the upconversion luminescence. This technology could be used for differentiation between acute infection from past infection and immunity. Additionally, the class of the antibody response can be used for the differentiation between primary and secondary infections, hence, facilitating epidemiological seroprevalence studies.
Vishal Kale, Henna PÃ¤kkilÃ¤, Jiri Vainio, Anna Ahomaa, Nina Sirkka, Annika LyytikÃ¤inen, Sheikh Mohammad Talha, Anna Kutsaya, Matti Waris, Ilkka Julkunen, Tero Soukka
2817 related Products with: Spectrally and Spatially Multiplexed Serological Array-in-Well Assay Utilizing Two-Color Upconversion Luminescence Imaging.96 Samples9 x 25 assays1 kit(96 Wells)1 kit(96 Wells)100 assays100tests1 kit500 assays1 kit(96 Wells)1 kit(96 Wells)
#26210958 2015/07/23 To Up
Antiadenovirus drug discovery: potential targets and evaluation methodologies.Human adenoviruses (HAdV) are the cause of many acute infections, mostly in the respiratory and gastrointestinal (GI) tracts, as well as conjunctivitis. HAdV diseases in immunocompetent individuals are mostly self-limiting; however, in immunocompromised individuals, especially in pediatric units, HAdV infections are the cause of high morbidity and mortality. Despite the significant clinical impact, there are currently no approved antiviral therapies for HAdV infections. Here, we provide an overview of the different targets that could be considered for the design of specific drugs against HAdV, as well as the available in vitro and in vivo tools for the screening and evaluation of candidate molecules.
Pablo MartÃnez-Aguado, Ana Serna-Gallego, JosÃ© A Marrugal-Lorenzo, Isabel GÃ³mez-MarÃn, Javier SÃ¡nchez-CÃ©spedes
1018 related Products with: Antiadenovirus drug discovery: potential targets and evaluation methodologies.25 mg100 assays10 mg100ug1 kit500 MG5mg
No related Items
#25763606 2015/04/02 To Up
TOA02, a recombinant adenovirus with tumor-specific granulocyte macrophage colony-stimulating factor expression, has limited biodistribution and low toxicity in rhesus monkeys.TOA02 is a genetically modified oncolytic adenovirus that contains human granulocyte macrophage colony-stimulating factor (hGM-CSF). It has been verified in vitro that TOA02 can specifically replicate in tumor cells that possess high telomerase reverse transcriptase activity and Rb pathway deficiency. However, the replication specificity, hGM-CSF expression, and toxicity of TOA02 in vivo are still unknown. Therefore, the biosafety of TOA02 remains a critical issue before its potential clinical use. In this study, viral replication and hGM-CSF expression levels were investigated in both xenograft nude mouse models and rhesus monkeys, and chronic toxicity was evaluated in rhesus monkeys. Our results show that (1) the replication and hGM-CSF expression of TOA02 are high in tumor model, (2) there are no hGM-CSF expression and continuous viral replication in rhesus monkeys except in pancreas and epididymis, and (3) the antiadenovirus antibody was positive in the chronic toxicity experiment, but pathological change of blood cytology and blood biochemistry were not found. There were no other histopathology lesions apart from skin inflammation of the administration region, lymphadenitis of draining lymph nodes. Our findings suggest that TOA02 is relatively safe for in vivo application, thus laying the foundation for future clinical trials with TOA02.
Ling Wang, Juecun Zheng, Qianchuan He, Xiaoping Yu, Xiaosong Hu, Shanshan Deng, Shuching Chang, Fubing Shen
2078 related Products with: TOA02, a recombinant adenovirus with tumor-specific granulocyte macrophage colony-stimulating factor expression, has limited biodistribution and low toxicity in rhesus monkeys.1 mg50 ug10 ug5ug1 mg50 ug5ug10 ug5ug2ug4 Membranes/Box
#24580050 2014/03/31 To Up
Adenovirus-based vaccines for fighting infectious diseases and cancer: progress in the field.The field of adenovirology is undergoing rapid change in response to increasing appreciation of the potential advantages of adenoviruses as the basis for new vaccines and as vectors for gene and cancer therapy. Substantial knowledge and understanding of adenoviruses at a molecular level has made their manipulation for use as vaccines and therapeutics relatively straightforward in comparison with other viral vectors. In this review we summarize the structure and life cycle of the adenovirus and focus on the use of adenovirus-based vectors in vaccines against infectious diseases and cancers. Strategies to overcome the problem of preexisting antiadenovirus immunity, which can hamper the immunogenicity of adenovirus-based vaccines, are discussed. When armed with tumor-associated antigens, replication-deficient and oncolytic adenoviruses can efficiently activate an antitumor immune response. We present concepts on how to use adenoviruses as therapeutic cancer vaccines and consider some of the strategies used to further improve antitumor immune responses. Studies that explore the prospect of adenoviruses as vaccines against infectious diseases and cancer are underway, and here we give an overview of the latest developments.
Dragomira Majhen, Hugo Calderon, Naresh Chandra, Carlos Alberto Fajardo, Anandi Rajan, Ramon Alemany, Jerome Custers
2078 related Products with: Adenovirus-based vaccines for fighting infectious diseases and cancer: progress in the field.500 tests500 tests500 tests500 tests500 tests500 tests500 tests
#26015963 2014/05/28 To Up
Biosafety studies of carrier cells infected with a replication-competent adenovirus introduced by IAI.3B promoter.The use of carrier cells infected with oncolytic viruses in cancer gene therapy is an attractive method because it can overcome viral immunogenicity and induce tumor immunity and significant antitumor activity. To enable human clinical trials of this treatment, acute and chronic toxicity tests must first be performed to ensure safety. IAI.3B promoter, oncolytic adenovirus AdE3-IAI.3B introduced by IAI.3B promoter, and A549 carrier cells infected with AdE3-IAI.3B were highly active in cancer cells but not in normal cells. Freeze-thawing increased the antitumor effect of A549 carrier cells by promoting the translocation of oncolytic adenovirus particles from the nucleus to the cytoplasm following the rupture of the nuclear membranes. No deaths or abnormal blood test data resulted from acute toxicity tests conducted in nude mice after a single dose. In chronic toxicity tests in rabbits, there were no serious side effects after eight doses of 1.25âÃâ10(7) cells/kg or less for 4 weeks; a significant immune response is known to elicit increased numbers of antiadenovirus antibodies and enlarge the spleen. From these results, it could be concluded that cancer gene therapy of recurrent solid tumors using carrier cells can be safely trialed in humans.
Katsuyuki Hamada, Toshiro Shirakawa, Shuji Terao, Akinobu Gotoh, Kenzaburo Tani, Wenlin Huang
2242 related Products with: Biosafety studies of carrier cells infected with a replication-competent adenovirus introduced by IAI.3B promoter.100 µg100 µg0.1ml (1mg/ml)1 mg100 µg1 mg100μl100ug Lyophilized100.00 ul1.5x10(6) cells100ug0.2 mg
#22855499 2012/08/01 To Up
Circumventing antivector immunity by using adenovirus-infected blood cells for repeated application of adenovirus-vectored vaccines: proof of concept in rhesus macaques.Adenovirus has been extensively exploited as a vector platform for delivering vaccines. However, preexisting antiadenovirus immunity is the major stumbling block for application of adenovirus-vectored vaccines. In this study, we found that freshly isolated peripheral blood mononuclear cells (PBMCs), mostly CD14(+) cells, from adenovirus serotype 5 (Ad5)-seropositive primates (humans and rhesus macaques) can be efficiently infected with Ad5 in vitro. On the basis of this observation, a novel strategy based on adenoviral vector-infected PBMC (AVIP) immunization was explored to circumvent antivector immunity. Autologous infusion of Ad5-SIVgag-infected PBMCs elicited a strong Gag-specific cellular immune response but induced weaker Ad5-neutralizing antibody (NAb) in Ad5-seronegative macaques than in macaques intramuscularly injected with Ad5-SIVgag. Moreover, Ad5-seropositive macaques receiving multiple AVIP immunizations with Ad5-SIVenv, Ad5-SIVgag, and Ad5-SIVpol vaccines elicited escalated Env-, Gag-, and Pol-specific immune responses after each immunization that were significantly greater than those in macaques intramuscularly injected with these Ad5-SIV vaccines. After challenged intravenously with a highly pathogenic SIVmac239 virus, macaques receiving AVIP immunization demonstrated a significant reduction in viral load at both the peak time and set-point period compared with macaques without Ad5-SIV vaccines. Our study warranted further research and development of the AVIP immunization as a platform for repeated applications of adenovirus-vectored vaccines.
Caijun Sun, Liqiang Feng, Yinfeng Zhang, Lijun Xiao, Weiqi Pan, Chufang Li, Linqi Zhang, Ling Chen
2807 related Products with: Circumventing antivector immunity by using adenovirus-infected blood cells for repeated application of adenovirus-vectored vaccines: proof of concept in rhesus macaques.100 µg100 µg1 mg100ug100ml1 ml100ug15ml100 ug0.1ml
#20386465 // To Up
Rapid generation of full clinical-grade human antiadenovirus cytotoxic T cells for adoptive immunotherapy.Adenovirus (ADV) infections are one of the major causes of morbidity and mortality after hematopoietic stem cell transplantation, despite new antiviral treatment strategies. We describe here a complete clinical-grade generation of human anti-ADV cytotoxic T cells to propose an adoptive immunotherapy. Peripheral blood mononuclear cells (PBMC) from 7 healthy donors, known for their good cellular immunity against ADV, were stimulated for 6 hours with a synthetic peptide pool covering the ADV5 Hexon protein interferon-gamma (IFN-gamma) secreting cells were isolated on a clinical device. After immunoselection, a mean number of 1.01 +/- 0.84 x 10(6) total nucleated cells was obtained. The isolated ADV-specific T cells were mainly CD4+ (mean=56% +/- 20.8%, yield=51% +/- 32.4%) but also CD8+ (mean=42% +/- 27%, yield = 56% +/- 39.3%). Isolated T lymphocytes (CTL) were expanded to carry out functional tests. Ability of the expanded CTL to secrete IFN-gamma and to proliferate after restimulation with the ADV peptide pool was confirmed. A high cytotoxicity against autologous target cells loaded with ADV antigens was observed but not against nonloaded target cells. We observed a decrease of 1.27 log of the allogeneic reaction against non HLA identical healthy donor PBMC with CTL compared with the PBMC before selection. Clinical-grade generation of ADV-specific T cells was achieved with a synthetic antigen. This technology has the advantage of being fast, and is sufficiently reactive to be proposed for immunotherapy if antiviral treatment fails.
Lamia AÃ¯ssi-RothÃ©, VÃ©ronique Decot, VÃ©ronique Venard, HÃ©lÃ¨ne Jeulin, Alexandra Salmon, Laurence Clement, Anne Kennel, Christine Mathieu, Jean Hugues Dalle, Georg Rauser, Christophe Cambouris, Marcelo de Carvalho, Jean FranÃ§ois Stoltz, Pierre Bordigoni, DaniÃ¨le Bensoussan
2583 related Products with: Rapid generation of full clinical-grade human antiadenovirus cytotoxic T cells for adoptive immunotherapy.
#19968324 // To Up
Anionic liposomes increase the efficiency of adenovirus-mediated gene transfer to coxsackie-adenovirus receptor deficient cells.Despite remarkable progress in the research of both viral and nonviral gene delivery vectors, the drawbacks in each delivery system have limited their clinical applications. Therefore, one of the concepts for developing novel vectors is to overcome the limitations of individual vectors by combining them. In the current study, adenoviral vectors were formulated with anionic liposomes to protect them from neutralizing antibodies and to improve their transduction efficiency in Coxsackievirus-adenovirus receptor (CAR) deficient cells. A calcium-induced phase change method was applied to encapsulate adenovirus 5 (Ad5) into anionic liposomes to formulate the complexes of Ad5 and anionic liposomes (Ad5-AL). Meanwhile, the complexes of Ad5 and cationic liposomes (Ad5-CL) were also prepared as controls. LacZ gene expression in CAR overexpressing cells (A549) and CAR deficient cells (CHO and MDCK) was measured by either qualitative or quantitative detection. Confocal laser scanning microscopy was performed to determine intracellular location of Ad5 after their infection. Human sera with a high titer of antiadenovirus antibody were used to assess the neutralizing antibody protection ability of the complexed vectors. Accompanying the enhanced gene expression, a high ability to introduce Ad5 into cytoplasm and nucleus mediated by Ad5-AL was also observed in CAR deficient cells. Additionally, antibody neutralizing assay indicated that neutralizing serum inhibited naked Ad5 and Ad5-CL at rather higher dilution than Ad5-AL, which demonstrated Ad5-AL was more capable of protecting Ad5 from neutralizing than Ad5-CL. In conclusion, anionic liposomes prepared by the calcium-induced phase change method could significantly enhance the transduction ability of Ad5 in CAR deficient cells.
Zhirong Zhong, Sanjun Shi, Jianfeng Han, Zhirong Zhang, Xun Sun
2263 related Products with: Anionic liposomes increase the efficiency of adenovirus-mediated gene transfer to coxsackie-adenovirus receptor deficient cells.100 ug/vial100μl200 ug100ug100ug100ug Lyophilized100 ug100ug1 ml1 ml100μg
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45 Fax 0032 16 50 90 45
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50 Fax 01 43 25 01 60
52062 Aachen Deutschland
Tel 0241 40 08 90 86 Fax 0241 55 91 05 36
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
Schweiz Züri +41435006251
Česká republika Praha +420246019719
Ireland Dublin +35316526556
Norge Oslo +4721031366
Finland Helsset +358942419041
Sverige Stockholm +46852503438
Ελλάς Αθήνα +302111768494
Magyarország Budapest +3619980547
GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
Tel 058 710 33 44
Fax 058 710 33 48
GENTAUR Nederland BV
5521 DG Eersel Nederland
Tel 0208-080893 Fax 0497-517897
Piazza Giacomo Matteotti, 6, 24122 Bergamo
Tel 02 36 00 65 93 Fax 02 36 00 65 94
53 Iskar Str. 1191 Kokalyane, Sofia