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https://www.readbyqxmd.com/read/28502294/-resiquimod-r848-has-more-stronger-immune-adjuvantivity-than-other-tested-tlr-agonists
#1
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
#2
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
#3
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
#4
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 HCO3(-) absorption in the medullary thick ascending limb (MTAL) through a basolateral TLR4-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 hr, then LPS was added to (and MPLA removed from) the bath solution...
March 29, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28161462/immune-response-and-protective-profile-elicited-by-a-multi-epitope-chimeric-protein-derived-from-leptospira-interrogans
#12
Luis G V Fernandes, Aline F Teixeira, Antonio F S Filho, Gisele O Souza, Silvio A Vasconcellos, Marcos B Heinemann, Eliete C Romero, Ana L T O Nascimento
INTRODUCTION: Pathogenic Leptospira is the causative agent of leptospirosis, a widely disseminated disease of human and veterinary concern. The development of vaccines that elicit cross-protective immunity through multiple leptospiral serovars has long been pursued. The aim of this study was to develop a novel chimeric multi-epitope fusion antigen, containing sequences of previously studied outer membrane proteins (OMPs) of Leptospira. METHODS: The chimeric protein was designed based on the amino acid sequences of the LigA, Mce, Lsa45, OmpL1, and LipL41 proteins, cloned into pAE vector, the protein expressed in Escherichia coli, and its immune response evaluated in the hamster infection model...
February 1, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28150207/nanotechnology-based-cancer-vaccine
#13
Aws Alshamsan
Nanotechnology offers invaluable tools to tailor cancer vaccines in order to generate robust antitumor immune response. Among the types of vehicles for cancer vaccines, nanoparticles (NPs) are easier to produce with better scalability. Several nanostructures have been discussed in literature as potential delivery systems for cancer antigens. Here, we focus on polymeric NPs fabricated from poly(D,L-lactic-co-glycolic) acid (PLGA). We describe how to prepare and characterize such NPs loaded with ovalbumin (OVA) antigen and immune adjuvant monophosphoryl lipid A (MPLA)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28114333/identification-of-balb-c-immune-markers-correlated-with-a-partial-protection-to-leishmania-infantum-after-vaccination-with-a-rationally-designed-multi-epitope-cysteine-protease-a-peptide-based-nanovaccine
#14
Maria Agallou, Maritsa Margaroni, Evita Athanasiou, Dimitra K Toubanaki, Katerina Kontonikola, Konstantina Karidi, Olga Kammona, Costas Kiparissides, Evdokia Karagouni
BACKGROUND: Through their increased potential to be engaged and processed by dendritic cells (DCs), nanovaccines consisting of Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with both antigenic moieties and adjuvants are attractive candidates for triggering specific defense mechanisms against intracellular pathogens. The aim of the present study was to evaluate the immunogenicity and prophylactic potential of a rationally designed multi-epitope peptide of Leishmania Cysteine Protease A (CPA160-189) co-encapsulated with Monophosphoryl lipid A (MPLA) in PLGA NPs against L...
January 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28093114/in-vitro-effects-of-the-toll-like-receptor-agonists-monophosphoryl-lipid-a-and-cpg-rich-oligonucleotides-on-cytokine-production-by-equine-cells
#15
A Ziegler, V Gerber, E Marti
Insect bite hypersensitivity (IBH) is an equine allergic dermatitis to Culicoides spp. antigens. Attempts at using allergen-specific immunotherapy (AIT) as a treatment for IBH have so far proven unsuccessful. Toll-like receptor (TLR) agonists can promote a shift in the immune response from the allergy-promoting T helper cell 2 (Th2) response towards a Th1 and/or regulatory response. The aim of this study was to evaluate two immunomodulatory TLR agonists in vitro as potential vaccine adjuvants for a more efficacious AIT in IBH...
January 2017: Veterinary Journal
https://www.readbyqxmd.com/read/28069966/inherited-human-irak-1-deficiency-selectively-impairs-tlr-signaling-in-fibroblasts
#16
Erika Della Mina, Alessandro Borghesi, Hao Zhou, Salim Bougarn, Sabri Boughorbel, Laura Israel, Ilaria Meloni, Maya Chrabieh, Yun Ling, Yuval Itan, Alessandra Renieri, Iolanda Mazzucchelli, Sabrina Basso, Piero Pavone, Raffaele Falsaperla, Roberto Ciccone, Rosa Maria Cerbo, Mauro Stronati, Capucine Picard, Orsetta Zuffardi, Laurent Abel, Damien Chaussabel, Nico Marr, Xiaoxia Li, Jean-Laurent Casanova, Anne Puel
Most members of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) families transduce signals via a canonical pathway involving the MyD88 adapter and the interleukin-1 receptor-associated kinase (IRAK) complex. This complex contains four molecules, including at least two (IRAK-1 and IRAK-4) active kinases. In mice and humans, deficiencies of IRAK-4 or MyD88 abolish most TLR (except for TLR3 and some TLR4) and IL-1R signaling in both leukocytes and fibroblasts. TLR and IL-1R responses are weak but not abolished in mice lacking IRAK-1, whereas the role of IRAK-1 in humans remains unclear...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28056837/vaccination-with-toxofilin-dna-in-combination-with-an-alum-monophosphoryl-lipid-a-mixed-adjuvant-induces-significant-protective-immunity-against-toxoplasma-gondii
#17
Pengxia Song, Shenyi He, Aihua Zhou, Gang Lv, Jingjing Guo, Jian Zhou, Yali Han, Huaiyu Zhou, Zhen Hao, Hua Cong
BACKGROUND: A widely prevalent disease, toxoplasmosis poses serious health threats to both humans and animals; therefore, development of an ideal DNA vaccine against Toxoplasma gondii is needed eagerly. The purpose of the present study is to assess the protective efficacy of a DNA vaccine encoding the T. gondii toxofilin gene (pEGFP-toxofilin). In addition, toxofilin DNA vaccine combined with the individual adjuvants, alum or monophosphoryl lipid A (MPLA), or a mixture of alum-MPLA adjuvant were screened for their ability to enhance antibody responses...
January 5, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28053314/comparative-transcriptome-profiles-of-human-blood-in-response-to-the-toll-like-receptor-4-ligands-lipopolysaccharide-and-monophosphoryl-lipid-a
#18
Liming Luan, Naeem K Patil, Yin Guo, Antonio Hernandez, Julia K Bohannon, Benjamin A Fensterheim, Jingbin Wang, Yaomin Xu, Perenlei Enkhbaatar, Ryan Stark, Edward R Sherwood
Monophosphoryl lipid A (MPLA), a less toxic derivative of lipopolysaccharide (LPS), is employed as a vaccine adjuvant and is under investigation as a non-specific immunomodulator. However, the differential response of human leukocytes to MPLA and LPS has not been well characterized. The goal of this study was to compare the differential transcriptomic response of human blood to LPS and MPLA. Venous blood from human volunteers was stimulated with LPS, MPLA or vehicle. Gene expression was determined using microarray analysis...
January 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28048733/mo-de-201-02-self-awareness
#19
J Johnson
Medical physicists possess technical knowledge and problem solving skills required to deliver high quality diagnosis and treatment in the clinic, to provide excellence in research, or to transfer expertise in industrial or regulatory environments. As the healthcare industry rapidly evolves, medical physicists must make a case for ensuring recognition of their value. One of many ways the AAPM is working to ensure stewardship of the profession is through development of the Medical Physics Leadership Academy (MPLA)...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28048232/mo-de-201-00-medical-physics-leadership-academy
#20
Jessica Clements
Medical physicists possess technical knowledge and problem solving skills required to deliver high quality diagnosis and treatment in the clinic, to provide excellence in research, or to transfer expertise in industrial or regulatory environments. As the healthcare industry rapidly evolves, medical physicists must make a case for ensuring recognition of their value. One of many ways the AAPM is working to ensure stewardship of the profession is through development of the Medical Physics Leadership Academy (MPLA)...
June 2016: Medical Physics
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