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https://www.readbyqxmd.com/read/28900154/synthesis-and-evaluation-of-gm2-monophosphoryl-lipid-a-conjugate-as-a-fully-synthetic-self-adjuvant-cancer-vaccine
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28487429/rationally-designed-tlr4-ligands-for-vaccine-adjuvant-discovery
#12
Kelsey A Gregg, Erin Harberts, Francesca M Gardner, Mark R Pelletier, Corinne Cayatte, Li Yu, Michael P McCarthy, Jason D Marshall, Robert K Ernst
Adjuvant properties of bacterial cell wall components like MPLA (monophosphoryl lipid A) are well described and have gained FDA approval for use in vaccines such as Cervarix. MPLA is the product of chemically modified lipooligosaccharide (LOS), altered to diminish toxic proinflammatory effects while retaining adequate immunogenicity. Despite the virtually unlimited number of potential sources among bacterial strains, the number of useable compounds within this promising class of adjuvants are few. We have developed bacterial enzymatic combinatorial chemistry (BECC) as a method to generate rationally designed, functionally diverse lipid A...
May 9, 2017: MBio
https://www.readbyqxmd.com/read/28356284/monophosphoryl-lipid-a-induces-protection-against-lps-in-medullary-thick-ascending-limb-through-a-tlr4-trif-pi3k-signaling-pathway
#13
Bruns A Watts, Thampi George, Edward R Sherwood, David W Good
Monophosphoryl lipid A (MPLA) is a detoxified derivative of LPS that induces tolerance to LPS and augments host resistance to bacterial infections. Previously, we demonstrated that LPS inhibits [Formula: see text] absorption in the medullary thick ascending limb (MTAL) through a basolateral Toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-ERK pathway. Here we examined whether pretreatment with MPLA would attenuate LPS inhibition. MTALs from rats were perfused in vitro with MPLA (1 µg/ml) in bath and lumen or bath alone for 2 h, and then LPS was added to (and MPLA removed from) the bath solution...
July 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28341814/the-effect-of-monophosphoryl-lipid-a-on-maturation-of-dcs-from-patients-with-acute-myeloid-leukaemia
#14
COMPARATIVE STUDY
Noha Mohamed El Husseiny, Walaa Abd El Fattah Attya Elkak, Mervat Said El Ansary, Engy Mohamed Abd El Aziz El Khateeb, Mervat Wagih Mattar, Doaa Mohamed El Demerdash
BACKGROUND: Generation of monocyte-derived dendritic cells (MDDC) is induced in the presence of GM-CSF and IL-4, and a maturation stimulus is added to the monocyte culture to obtain mature Dendritic Cells (DCs) suitable for therapy. TNF-α is the most common cytokine used for activating DCs and generating mature MDDC either alone or in combination with other cytokines. OBJECTIVE: To compare effects of traditional cytokine cocktail (TNF-α + IL-1β) versus TLR4-agonist monophosphoryl lipid A on the viability, phenotype, cytokine profile and functionality of MDDC...
March 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28316130/simultaneous-use-of-multiplex-ligation-dependent-probe-amplification-assay-and-flow-cytometric-dna-ploidy-analysis-in-patients-with-acute-leukemia
#15
Virginia Reyes-Núñez, Evelyn Galo-Hooker, Beatriz Pérez-Romano, Ricardo E Duque, Alejandro Ruiz-Arguelles, Javier Garcés-Eisele
BACKGROUND: The aim of this work was to simultaneously use multiplex ligation-dependent probe amplification (MLPA) assay and flow cytometric DNA ploidy analysis (FPA) to detect aneuploidy in patients with newly diagnosed acute leukemia. METHODS: MLPA assay and propidium iodide FPA were used to test samples from 53 consecutive patients with newly diagnosed acute leukemia referred to our laboratory for immunophenotyping. Results were compared by nonparametric statistics...
March 18, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28285019/quantitation-of-monophosphorylated-lipid-a-in-the-oil-in-water-adjuvant-delivery-systems-using-transesterification-and-gc-ms
#16
M Athar Masood, Josip Blonder, Timothy D Veenstra
Vaccine delivery systems play pivotal role in effective antigen delivery. These systems often contain adjuvants that stimulate specific immune response and are important for vaccines' efficacy and safety. Oil-in-water vaccine delivery lipid emulsion systems containing monophosphoryl lipid A (MPLA) as immune modulator have been extensively investigated in vaccine trials. Herein, we describe a simple orthogonal method, for quantitative measurement of MPLA in an oil-in-water lipid delivery system using direct transesterification reaction followed by gas-chromatography-mass spectrometry analysis...
March 8, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28275139/the-cytokine-response-to-lipopolysaccharide-does-not-predict-the-host-response-to-infection
#17
Benjamin A Fensterheim, Yin Guo, Edward R Sherwood, Julia K Bohannon
The magnitude of the LPS-elicited cytokine response is commonly used to assess immune function in critically ill patients. A suppressed response, known as endotoxin tolerance, is associated with worse outcomes, yet endotoxin tolerance-inducing TLR4 ligands are known to protect animals from infection. Thus, it remains unknown whether the magnitude of the LPS-elicited cytokine response provides an accurate assessment of antimicrobial immunity. To address this, the ability of diverse TLR ligands to modify the LPS-elicited cytokine response and resistance to infection were assessed...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28249007/safety-evaluation-of-a-vaccine-effect-in-maternal-reproductive-outcome-and-fetal-anomaly-frequency-in-rats-using-a-leishmanial-vaccine-as-a-model
#18
Rafaianne Q Moraes-Souza, Ana Paula Reinaque, Thaigra S Soares, Ana Luiza T Silva, Rodolfo C Giunchetti, Maria A S Takano, Milena A Akamatsu, Flávia S Kubrusly, Fernanda Lúcio-Macarini, Isaias Raw, Dmitri Iourtov, Paulo Lee Ho, Lilian L Bueno, Ricardo T Fujiwara, Gustavo T Volpato
While the immunogenic potential of the vaccination against infectious diseases was extensively shown, data on the safety assessment of recombinant proteins in vaccine formulations administered during pregnancy are still scarce. In the current study, the antigenicity of a vaccine against leishmaniasis (based on Leishmania braziliensis recombinant protein peroxidoxin) during pregnancy and possible maternal reproductive outcomes and fetal anomalies after immunization with a leishmanial vaccine or adjuvant alone (Bordetella pertussis derived MPLA adjuvant) were assessed...
2017: PloS One
https://www.readbyqxmd.com/read/28214044/enhancement-of-antigen-specific-cd4-and-cd8-t-cell-responses-using-a-self-assembled-biologic-nanolipoprotein-particle-vaccine
#19
Dina Weilhammer, Alexis D Dunkle, Craig D Blanchette, Nicholas O Fischer, Michele Corzett, Doerte Lehmann, Tyler Boone, Paul Hoeprich, Adam Driks, Amy Rasley
To address the need for vaccine platforms that induce robust cell-mediated immunity, we investigated the potential of utilizing self-assembling biologic nanolipoprotein particles (NLPs) as an antigen and adjuvant delivery system to induce antigen-specific murine T cell responses. We utilized OT-I and OT-II TCR-transgenic mice to investigate the effects of NLP-mediated delivery of the model antigen ovalbumin (OVA) on T cell activation. Delivery of OVA with the TLR4 agonist monophosphoryl lipid A (MPLA) in the context of NLPs significantly enhanced the activation of both CD4(+) and CD8(+) T cells in vitro compared to co-administration of free OVA and MPLA...
February 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28212807/prevalence-of-brca1-and-brca2-large-genomic-rearrangements-in-tunisian-high-risk-breast-ovarian-cancer-families-implications-for-genetic-testing
#20
Aouatef Riahi, Habiba Chabouni-Bouhamed, Maher Kharrat
Germline mutations in the BRCA tumor suppressor genes account for a substantial proportion of hereditary breast/ovarian cancer. However, this contribution is lower than expected. This underestimation can partly be explained by the BRCA alterations missed by using Sanger sequencing methods. Thus, large genomic rearrangements (LGRs) in BRCA1 and BRCA2 are responsible for 4-28% of all inherited BRCA mutations. In this study, Multiplex ligation-dependent probe amplification (MLPA) assay was used for detection of large rearrangements of BRCA1 and BRCA2 genes in 36 unrelated high-risk breast/ovarian cancer patients negative for BRCA1/2 point mutations...
January 2017: Cancer Genetics
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