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https://www.readbyqxmd.com/read/29156775/monophosphoryl-lipid-a-attenuates-radiation-injury-through-tlr4-activation
#1
Jiaming Guo, Yuanyuan Chen, Xiao Lei, Yang Xu, Zhe Liu, Jianming Cai, Fu Gao, Yanyong Yang
Ionizing radiation causes severe damage to human body, and normal tissue toxicity in cancer radiotherapy also limits its further application. It is urgently required to develop safe and effective radioprotector. Our previous study has shown that toll like receptor 4 (TLR4) was dispensable for basal radiation resistance. However, severe toxicity of its traditional agonist lipopolysaccharide limits the clinical application. In present study, we demonstrated that monophosphoryl lipid A (MPLA), a potent TLR4 agonist with low toxicity, effectively attenuated radiation injury on in vitro and in vivo...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29112822/synthesis-and-immunological-comparison-of-differently-linked-lipoarabinomannan-oligosaccharide-monophosphoryl-lipid-a-conjugates-as-antituberculosis-vaccines
#2
Lizhen Wang, Shaojie Feng, Subo Wang, Hui Li, Zhongwu Guo, Guofeng Gu
A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. The same tetrasaccharide was also coupled with MPLA at the 1-O-position. Immunological activities of the two synthetic conjugates were evaluated in mice and compared. Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection...
November 20, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/29109727/dexamethasone-and-monophosphoryl-lipid-a-induce-a-distinctive-profile-on-monocyte-derived-dendritic-cells-through-transcriptional-modulation-of-genes-associated-with-essential-processes-of-the-immune-response
#3
Paulina A García-González, Katina Schinnerling, Alejandro Sepúlveda-Gutiérrez, Jaxaira Maggi, Ahmed M Mehdi, Hendrik J Nel, Bárbara Pesce, Milton L Larrondo, Octavio Aravena, María C Molina, Diego Catalán, Ranjeny Thomas, Ricardo A Verdugo, Juan C Aguillón
There is growing interest in the use of tolerogenic dendritic cells (tolDCs) as a potential target for immunotherapy. However, the molecular bases that drive the differentiation of monocyte-derived DCs (moDCs) toward a tolerogenic state are still poorly understood. Here, we studied the transcriptional profile of moDCs from healthy subjects, modulated with dexamethasone (Dex) and activated with monophosphoryl lipid A (MPLA), referred to as Dex-modulated and MPLA-activated DCs (DM-DCs), as an approach to identify molecular regulators and pathways associated with the induction of tolerogenic properties in tolDCs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29091097/stereocomplexed-physical-hydrogels-with-high-strength-and-tunable-crystallizability
#4
Heqing Cao, Xiaohua Chang, Hailiang Mao, Jian Zhou, Zi Liang Wu, Guorong Shan, Yongzhong Bao, Pengju Pan
Physical hydrogels crosslinked by non-covalent interactions have attained increasing attention due to their good mechanical properties and processability. However, the use of feasible and controllable non-covalent interactions is highly essential for preparing such hydrogels. In this article, we report on stereocomplexed physical hydrogels prepared by simple casting and swelling of amphiphilic graft copolymers bearing a poly(acrylic acid) (PAA) backbone and poly(l-lactic acid) (PLLA) or poly(d-lactic acid) (PDLA) stereocomplexable side chains...
November 1, 2017: Soft Matter
https://www.readbyqxmd.com/read/29089195/superior-immunogenicity-of-hcv-envelope-glycoproteins-when-adjuvanted-with-cyclic-di-amp-a-sting-activator-or-archaeosomes
#5
A Landi, J Law, D Hockman, M Logan, K Crawford, C Chen, J Kundu, T Ebensen, C A Guzman, L Deschatelets, L Krishnan, D L J Tyrrell, M Houghton
Three decades after the discovery, hepatitis C virus (HCV) is still the leading cause of liver transplantation and poses a major threat to global health. In spite of recent advances in the development of direct acting antivirals, there is still a need for a prophylactic vaccine to limit the virus spread and protect at-risk populations, especially in developing countries, where the cost of the new treatments may severely limit access. The use of recombinant HCV glycoproteins E1E2 (rE1E2) in combination with the MF59, an oil-in-water emulsion-based adjuvant, has previously been shown to reduce the rate of chronicity in chimpanzees and to induce production of cross-neutralizing antibodies and cellular immune responses in human volunteers...
October 28, 2017: Vaccine
https://www.readbyqxmd.com/read/29073183/adjuvants-and-the-vaccine-response-to-the-ds-cav1-stabilized-fusion-glycoprotein-of-respiratory-syncytial-virus
#6
Mallika Sastry, Baoshan Zhang, Man Chen, M Gordon Joyce, Wing-Pui Kong, Gwo-Yu Chuang, Kiyoon Ko, Azad Kumar, Chiara Silacci, Michelle Thom, Andres M Salazar, Davide Corti, Antonio Lanzavecchia, Geraldine Taylor, John R Mascola, Barney S Graham, Peter D Kwong
Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively...
2017: PloS One
https://www.readbyqxmd.com/read/28992509/liposomes-coated-gold-nanocages-with-antigens-and-adjuvants-targeted-delivery-to-dendritic-cells-for-enhancing-antitumor-immune-response
#7
Ruijing Liang, Jun Xie, Jun Li, Ke Wang, Liping Liu, Yujie Gao, Mubashir Hussain, Guanxin Shen, Jintao Zhu, Juan Tao
For nanovaccine-based cancer immunotherapy, dendritic cells (DCs) are one of the most powerful antigen presenting cells (APCs) that initiate and promote the maturation of antigen-specific cytotoxic T lymphocytes (e.g., CD8(+) T cells) to induce the local and systemic antitumor immunity and further suppress the tumor metastasis and produce long-term protection against tumor. Thus, the activation and maturation of DCs is the prerequisite for efficient CD8(+) T cell-based antitumor immune responses, which is considered as a primary and promising task for nanovaccine engineering...
September 26, 2017: Biomaterials
https://www.readbyqxmd.com/read/28987878/co-delivery-of-nucleoside-modified-mrna-and-tlr-agonists-for-cancer-immunotherapy-restoring-the-immunogenicity-of-immunosilent-mrna
#8
Rein Verbeke, Ine Lentacker, Laura Wayteck, Karine Breckpot, Mieke Van Bockstal, Benedicte Descamps, Christian Vanhove, Stefaan C De Smedt, Heleen Dewitte
This study reports on the design of mRNA and adjuvant-loaded lipid nanoparticles for therapeutic cancer vaccination. The use of nucleoside-modified mRNA has previously been shown to improve the translational capacity and safety of mRNA-therapeutics, as it prevents the induction of type I interferons (IFNs). However, type I IFNs were identified as the key molecules that trigger the activation of antigen presenting cells, and as such drive T cell immunity. We demonstrate that nucleoside-modified mRNA can be co-delivered with the clinically approved TLR agonist monophosphoryl lipid A (MPLA)...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28955328/co-delivery-of-dual-toll-like-receptor-agonists-and-antigen-in-poly-lactic-co-glycolic-acid-polyethylenimine-cationic-hybrid-nanoparticles-promote-efficient-in-vivo-immune-responses
#9
Mahboubeh Ebrahimian, Maryam Hashemi, Mohsen Maleki, Gholamreza Hashemitabar, Khalil Abnous, Mohammad Ramezani, Alireza Haghparast
Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28900154/synthesis-and-evaluation-of-gm2-monophosphoryl-lipid-a-conjugate-as-a-fully-synthetic-self-adjuvant-cancer-vaccine
#10
Zhifang Zhou, Satadru S Mandal, Guochao Liao, Jiatong Guo, Zhongwu Guo
An efficient method was developed for the synthesis of a GM2 derivative suitable for the conjugation with various biomolecules. This GM2 derivative was covalently linked to keyhole limpet hemocyanin (KLH) and monophosphoryl lipid A (MPLA) to form novel therapeutic cancer vaccines. Immunological evaluations of the resultant conjugates in mice revealed that they elicited robust GM2-specific overall and IgG antibody responses. Moreover, the GM2-MPLA conjugate was disclosed to elicit strong immune responses without the use of an adjuvant, proving its self-adjuvant property...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883727/vaccination-with-poly-d-l-lactide-co-glycolide-nanoparticles-loaded-with-soluble-leishmania-antigens-and-modified-with-a-tnf%C3%AE-mimicking-peptide-or-monophosphoryl-lipid-a-confers-protection-against-experimental-visceral-leishmaniasis
#11
Maritsa Margaroni, Maria Agallou, Evita Athanasiou, Olga Kammona, Costas Kiparissides, Catherine Gaitanaki, Evdokia Karagouni
Visceral leishmaniasis (VL) persists as a major public health problem, and since the existing chemotherapy is far from satisfactory, development of an effective vaccine emerges as the most appropriate strategy for confronting VL. The development of an effective vaccine relies on the selection of the appropriate antigen and also the right adjuvant and/or delivery vehicle. In the present study, the protective efficacy of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface-modified with a TNFα-mimicking eight-amino-acid peptide (p8) and further functionalized by encapsulating soluble Leishmania infantum antigens (sLiAg) and monophosphoryl lipid A (MPLA), a TLR4 ligand, was evaluated against challenge with L...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28837901/the-effect-of-prr-ligands-on-the-membrane-potential-of-intestinal-epithelial-cells
#12
Diogo Magalhães, Patrício Soares-da-Silva, Fernando Magro
BACKGROUND: Disproportionate signaling through intestinal epithelial pattern recognition receptors (PRR) plays a role in IBD (inflammatory bowel disease) pathophysiology. Diarrhea is a clinical trademark of IBD and altered activity of K(+) channels (KC) may contribute to the low sodium absorption state. Here we sought to study the impact of PRR activation on the membrane potential of human intestinal epithelial cells and the role of KC in it. METHODS: All assays were performed in cultured HT-29 cells...
April 23, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28745674/-gene-mutations-in-patients-with-hereditary-cavernous-malformations
#13
O B Belousova, E S Bulygina, D N Okishev, E B Prohorchuk, S V Tsygankova, I N Pronin, L V Shishkina, M V Ryzhova, K G Skryabin, A N Konovalov
AIM: To identify mutations in cerebral cavernous malformation (CCM) genes in patients with hereditary and sporadic CCMs in the Russian population. MATERIAL AND METHODS: Blood samples from 73 randomly selected patients, including 29 MRI-confirmed familial cases, 8 clinically confirmed familial cases and 38 so-called sporadic cases, were examined. A search for large deletions/duplications was performed using multiplex ligation-dependent probe amplification (MPLA)...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28708895/yeast-expressed-recombinant-as16-protects-mice-against-ascaris-suum-infection-through-induction-of-a-th2-skewed-immune-response
#14
Junfei Wei, Leroy Versteeg, Zhuyun Liu, Brian Keegan, Ana Clara Gazzinelli-Guimarães, Ricardo T Fujiwara, Neima Briggs, Kathryn M Jones, Ulrich Strych, Coreen M Beaumier, Maria Elena Bottazzi, Peter J Hotez, Bin Zhan
BACKGROUND: Ascariasis remains the most common helminth infection in humans. As an alternative or complementary approach to global deworming, a pan-anthelminthic vaccine is under development targeting Ascaris, hookworm, and Trichuris infections. As16 and As14 have previously been described as two genetically related proteins from Ascaris suum that induced protective immunity in mice when formulated with cholera toxin B subunit (CTB) as an adjuvant, but the exact protective mechanism was not well understood...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28676095/toll-like-receptor-4-stimulation-with-monophosphoryl-lipid-a-ameliorates-motor-deficits-and-nigral-neurodegeneration-triggered-by-extraneuronal-%C3%AE-synucleinopathy
#15
Serena Venezia, Violetta Refolo, Alexia Polissidis, Leonidas Stefanis, Gregor K Wenning, Nadia Stefanova
BACKGROUND: Alpha-synuclein (α-syn) aggregation represents the pathological hallmark of α-synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Toll-like receptors (TLRs) are a family of highly conserved molecules that recognize pathogen-associated molecular patterns and define the innate immunity response. It was previously shown that TLR4 plays a role in the clearance of α-syn, suggesting that TLR4 up-regulation in microglia may be a natural mechanism to improve the clearance of α-syn...
July 4, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28659922/a-poly-lactic-co-glycolic-acid-nanovaccine-based-on-chimeric-peptides-from-different-leishmania-infantum-proteins-induces-dendritic-cells-maturation-and-promotes-peptide-specific-ifn%C3%AE-producing-cd8-t-cells-essential-for-the-protection-against-experimental-visceral
#16
Evita Athanasiou, Maria Agallou, Spyros Tastsoglou, Olga Kammona, Artemis Hatzigeorgiou, Costas Kiparissides, Evdokia Karagouni
Visceral leishmaniasis, caused by Leishmania (L.) donovani and L. infantum protozoan parasites, can provoke overwhelming and protracted epidemics, with high case-fatality rates. An effective vaccine against the disease must rely on the generation of a strong and long-lasting T cell immunity, mediated by CD4(+) TH1 and CD8(+) T cells. Multi-epitope peptide-based vaccine development is manifesting as the new era of vaccination strategies against Leishmania infection. In this study, we designed chimeric peptides containing HLA-restricted epitopes from three immunogenic L...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28641125/an-altered-redox-environment-assisted-by-over-expression-of-fetal-hemoglobins-protects-from-inflammatory-colitis-and-reduces-inflammatory-cytokine-expression
#17
R M Gorczynski, C Alexander, K Brandenburg, Z Chen, A Heini, D Neumann, J P Mach, E T Rietschel, A Tersikh, A J Ulmer, Kai Yu, U Zahringer, I Khatri
C5BL/6 female mice receiving dextran sodium sulfate in their drinking water develop an acute inflammatory colitis within 7d, with weight loss, histopathologic signs of inflammation, and colonic expression of inflammatory cytokines. In previous studies we have reported that increased inflammatory cytokine expression in aged mice can be attenuated by oral gavage of a crude fetal extract containing glutathione (GSH), MPLA and fetal hemoglobin, or more specifically by injection of a combination of these purified reagents...
June 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28572807/a-new-adjuvant-mtom-mediates-mycobacterium-tuberculosis-subunit-vaccine-to-enhance-th1-type-t-cell-immune-responses-and-il-2-t-cells
#18
Qi Yu, Xiaochun Wang, Xionglin Fan
The only licensed vaccine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) cannot prevent the prevalence of tuberculosis (TB), which remains a major public health problem worldwide. A more effective TB vaccine than BCG is urgently needed. Subunit vaccine is a promising strategy, and suitable adjuvants will benefit the development of effective TB subunit vaccines. MTO, consisting of monophosphoryl lipid A (MPLA), trehalose-6,6'-dibehenate (TDB), and MF59, was developed as an adjuvant of TB vaccine because of its ability to evoke the Th1-type T cell responses, while it is insufficient to induce single and multifunctional IL-2(+) T cells and has a limited ability to confer protection against Mycobacterium tuberculosis infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28502294/-resiquimod-r848-has-more-stronger-immune-adjuvantivity-than-other-tested-tlr-agonists
#19
Yuan Shen, Menghua Zeng, Feng Qiu, Hua Tang
Objective To compare and characterize the Th1 immune responses induced by the most commonly used commercial Toll-like receptor (TLR) agonists through in vivo and ex vivo experiments. Methods The concentrations of IL-12 were tested by ELISA after mouse dendritic cells (DCs) in vitro were stimulated by one of tested TLR agonists, including poly(I:C), monophosphoryl lipid A (MPLA), resiquimod (R848), cytosine polyguanine-C (CpG-C). The changes in percentage and phenotype of DCs, NK cells and effector T cells in the draining lymph nodes were analyzed by flow cytometry after BALB/c mice were immunized with ovalbumin (OVA) mixed with selected TLR agonist...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28502107/a-nano-particle-vector-comprised-of-poly-lactic-co-glycolic-acid-and-monophosphoryl-lipid-a-and-recombinant-mycobacterium-avium-subsp-paratuberculosis-peptides-stimulate-a-pro-immune-profile-in-bovine-macrophages
#20
Cleverson D Souza, John P Bannantine, Wendy C Brown, M Grant Norton, William C Davis, Julianne K Hwang, Parissa Ziaei, Gaber S Abdellrazeq, Meaghan V Eren, James R Deringer, Elizabeth Laws, Maria Clara D Cardieri
AIMS: We evaluated the potential of a nanoparticle (NP) delivery system to improve methods of delivery of candidate peptide based vaccines for Paratuberculosis in cattle. METHODS AND RESULTS: Peptides derived from Mycobacterium avium subsp paratuberculosis (Map), and the proinflammatory monophosphoryl lipid A (MPLA) were incorporated in polymeric NPs based on poly (D, L-lactide-co-glycolide) (PLGA). The PLGA/MPLA NPs carriers were incubated with macrophages to examine their effects on survival and function...
May 14, 2017: Journal of Applied Microbiology
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