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https://www.readbyqxmd.com/read/28734176/cancer-immunotherapy-moving-forward-with-peptide-t-cell-vaccines
#1
REVIEW
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28734174/old-and-new-adjuvants
#2
REVIEW
Amy S McKee, Philippa Marrack
Adjuvants have been deliberately added to vaccines since the 1920's when alum was discovered to boost antibody responses, leading to better protection. The first adjuvants were discovered by accident and were used in the safer but less immunogenic subunit vaccines, supposedly by providing an antigen depot to extend antigen presentation. Since that time, much has been discovered about how these adjuvants impact cells at the tissue site to activate innate immune responses, mobilize dendritic cells and drive adaptive immunity...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732435/the-effect-of-oral-levamisole-co-administration-on-the-level-of-immune-response-to-hepatitis-b-vaccine-in-healthy-individuals-a-randomized-clinical-trial
#3
Mousalreza Hosseini, Payman Shalchiantabrizi, Maliheh Dadgarmoghaddam, Saeideh Ahmady-Simab, Azizollah Behjati, Masoumeh Salari
Despite its proven efficacy, the hepatitis B vaccine requires improvements in immune enhancement and durability, especially in the elderly. Levamisole, an immune modulator, has been tested as an adjuvant to hepatitis B vaccine in several studies in immune-compromised populations. However, we aimed to evaluate the effect of levamisole on the immune response to hepatitis B vaccine in healthy subjects. In this randomized clinical trial, healthy family members of chronic hepatitis B patients were given twenty-microgram intramuscular injections of hepatitis B vaccine at 0, 1, and 6 months and 50 miligrams of oral  levamisole twice a day for two weeks with every vaccination dose...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#4
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28731898/steady-progress-toward-a-malaria-vaccine
#5
Kirsten E Lyke
PURPOSE OF REVIEW: Great progress has been made in reducing malaria morbidity and mortality, yet the parasite continues to cause a startling 200 million infections and 500 000 deaths annually. Malaria vaccine development is pushing new boundaries by steady advancement toward a licensed product. RECENT FINDINGS: Despite 50 years of research, the complexity of Plasmoidum falciparum confounds all attempts to eradicate the organism. This very complexity has pushed the boundaries of vaccine development to new heights, yet it remains to be seen if an affordable vaccine can provide durable and high-level protection...
July 20, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28730433/computational-prediction-of-the-immunomodulatory-potential-of-rna-sequences
#6
Gandharva Nagpal, Kumardeep Chaudhary, Sandeep Kumar Dhanda, Gajendra Pal Singh Raghava
Advances in the knowledge of various roles played by non-coding RNAs have stimulated the application of RNA molecules as therapeutics. Among these molecules, miRNA, siRNA, and CRISPR-Cas9 associated gRNA have been identified as the most potent RNA molecule classes with diverse therapeutic applications. One of the major limitations of RNA-based therapeutics is immunotoxicity of RNA molecules as it may induce the innate immune system. In contrast, RNA molecules that are potent immunostimulators are strong candidates for use in vaccine adjuvants...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28729715/inflammatory-monocytes-regulate-th1-oriented-immunity-to-cpg-adjuvanted-protein-vaccines-through-production-of-il-12
#7
S De Koker, L Van Hoecke, A De Beuckelaer, K Roose, K Deswarte, M A Willart, P Bogaert, T Naessens, B G De Geest, X Saelens, B N Lambrecht, J Grooten
Due to their capacity to skew T cell responses towards Th1 oriented immunity, oligonucleotides containing unmethylated CpG motifs (CpG) have emerged as interesting adjuvants for vaccination. Whereas the signalling pathways in response to CpG mediated TLR9 activation have been extensively documented at the level of the individual cell, little is however known on the precise identity of the innate immune cells that govern T cell priming and polarisation to CpG adjuvanted protein antigens in vivo. In this study, we demonstrate that optimal induction of Th1 oriented immunity to CpG adjuvanted protein vaccines requires the coordinated actions of conventional DCs and of monocytes...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728074/no-pain-no-gain-adjuvant-effects-of-alum-and-monophosphoryl-lipid-a-in-pertussis-and-hpv-vaccines
#8
REVIEW
Thomas C Mitchell, Carolyn R Casella
Development of non-infectious subunit vaccines is hampered by a slow pipeline of new adjuvants to replace or enhance alum in part because expectations of safety are high. Transient vaccine side effects are not clinical priorities because they cause no lasting harm and vaccine development has appropriately been focused on avoidance of serious adverse events. As a result, surprisingly little is known about the extent to which side effects caused by a vaccine's reactogencicity are predictive of successful immunization outcomes...
July 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28726424/self-encapsulating-poly-lactic-co-glycolic-acid-plga-microspheres-for-intranasal-vaccine-delivery
#9
Brittany A Bailey, Kashappa-Goud H Desai, Lukasz J Ochyl, Susan M Ciotti, James J Moon, Steven P Schwendeman
Herein we describe a formulation of self-encapsulating poly(lactic-co-glycolic acid) (PLGA) microspheres for vaccine delivery. Self-healing encapsulation is a novel encapsulation method developed by our group that enables the aqueous loading of large molecules into pre-made PLGA microspheres. Calcium phosphate (CaHPO4) adjuvant gel was incorporated into the microspheres as a protein-trapping agent for improved encapsulation of antigen. Microspheres were found to have a median size of 7.05 ± 0.31 µm, with a w/w loading of 0...
July 20, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28725225/antiviral-functions-of-human-immunodeficiency-virus-type-1-hiv-1-specific-igg-antibodies-effects-of-antiretroviral-therapy-and-implications-for-therapeutic-hiv-1-vaccine-design
#10
REVIEW
Martyn A French, M Christian Tjiam, Laila N Abudulai, Sonia Fernandez
Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting "protective" HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28725106/development-of-porcine-circovirus-2-pcv2-open-reading-frame-2-dna-vaccine-with-different-adjuvants-and-comparison-with-commercial-pcv2-subunit-vaccine-in-an-experimental-challenge
#11
Changhoon Park, Jiwoon Jeong, Kyuhyung Choi, Su-Jin Park, Ikjae Kang, Chanhee Chae
The objective of this study was to compare the protection against challenge with porcine circovirus 2 (PCV2) induced by an experimental vaccine based on open reading frame (ORF) 2 of PCV2 DNA plus an adjuvant (aluminum hydroxide, cobalt oxide, or liposome) and a commercial PCV2 subunit vaccine. A total of 35 colostrum-fed, cross-bred, conventional piglets were randomly divided into 7 groups. The commercial vaccine was more efficacious against PCV2 challenge than the 4 experimental vaccines according to immunologic, virologic, and pathological outcomes...
July 2017: Canadian Journal of Veterinary Research, Revue Canadienne de Recherche Vétérinaire
https://www.readbyqxmd.com/read/28724973/alternatives-to-mineral-oil-adjuvants-in-vaccines-against-aeromonas-salmonicida-subsp-salmonicida-in-rainbow-trout-offer-reductions-in-adverse-effects
#12
Kasper Rømer Villumsen, Erling Olaf Koppang, Dennis Christensen, Anders Miki Bojesen
In an effort to reduce the frequency and severity of adverse reactions seen from the use of mineral oil adjuvants in salmonid fish, the effects of two alternative adjuvants were assessed, focusing on the induction of adverse effects as well as protection. Using rainbow trout (Oncorhynchus mykiss) as recipients, injection vaccines based on formalin-inactivated Aeromonas salmonicida subspecies salmonicida were formulated with CpG oligodeoxynucleotides, the liposomal cationic adjuvant formulation 01 (CAF01) or with Freund's incomplete adjuvant and administered intraperitoneally...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724768/synthetic-tlr4-and-tlr7-ligands-work-additively-via-myd88-to-induce-protective-antiviral-immunity-in-mice
#13
Peter H Goff, Tomoko Hayashi, Wenqian He, Shiyin Yao, Howard B Cottam, Gene S Tan, Brian Crain, Florian Krammer, Karen Messer, Minya Pu, Dennis A Carson, Peter Palese, Maripat Corr
We have previously demonstrated that the combination of synthetic small molecule Toll-like receptor 4 (TLR4) and TLR7 ligands is a potent adjuvant for recombinant influenza virus hemagglutinin, inducing rapid and sustained immunity protective against influenza viruses in homologous, heterologous and heterosubtypic murine challenge models. Combining TLR4 and TLR7 ligands balances Th1/Th2-type immune responses for long-lived cellular and neutralizing humoral immunity against the viral hemagglutinin. Here, we demonstrate that the protective response induced in mice by this combined adjuvant is dependent upon TLR4 and TLR7 signaling via myeloid differentiation primary response gene 88 (MyD88), indicating that the adjuvants function in vivo via their known receptors with negligible off-target effects to induce protective immunity...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28723962/surface-functionalization-specific-binding-of-coagulation-factors-by-zinc-oxide-nanoparticles-delays-coagulation-time-and-reduces-thrombin-generation-potential-in-vitro
#14
Jun-Young Yang, Jiyeong Bae, Ayoung Jung, Seonyeong Park, Seungtae Chung, Jihyun Seok, Hangsik Roh, Youngju Han, Jae-Min Oh, Soojung Sohn, Jayoung Jeong, Wan-Seob Cho
Zinc oxide nanoparticles (ZnO NPs) have many biomedical applications such as chemotherapy agents, vaccine adjuvants, and biosensors but its hemocompatibility is still poorly understood, especially in the event of direct contact of NPs with blood components. Here, we investigated the impact of size and surface functional groups on the platelet homeostasis. ZnO NPs were synthesized in two different sizes (20 and 100 nm) and with three different functional surface groups (pristine, citrate, and L-serine). ZnO NPs were incubated with plasma collected from healthy rats to evaluate the coagulation time, kinetics of thrombin generation, and profile of levels of coagulation factors in the supernatant and coronated onto the ZnO NPs...
2017: PloS One
https://www.readbyqxmd.com/read/28721849/effective-protection-of-mice-against-shigella-flexneri-with-a-new-self-adjuvant-multicomponent-vaccine
#15
Yadira Pastor, Ana Camacho, Ana Gloria Gil, Rocío Ramos, Adela López de Ceráin, Iván Peñuelas, Juan M Irache, Carlos Gamazo
PURPOSE: The aim of this study was to develop an immunogenic protective product against Shigella flexneri by employing a simple and safe heat treatment-based strategy. METHODOLOGY: The physicochemical characteristics of naturally produced (OMV) and heat-induced (HT) outer-membrane vesicles from S. flexneri were examined, including a comparison of the protein content of the products. Toxicological and biodistribution studies, and a preliminary experiment to examine the protective effectiveness of HT in a murine model of S...
July 18, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28720281/evaluation-of-a-primary-course-of-h9n2-vaccine-with-or-without-as03-adjuvant-in-adults-a-phase-i-ii-randomized-trial
#16
Anuradha Madan, Harry Collins, Eric Sheldon, Louise Frenette, Laurence Chu, Damien Friel, Mamadou Drame, David W Vaughn, Bruce L Innis, Anne Schuind
BACKGROUND: Avian influenza A H9N2 strains have pandemic potential. METHODS: In this randomized, observer-blind study (ClinicalTrials.gov: NCT01659086), 420 healthy adults, 18-64years of age, received 1 of 10 H9N2 inactivated split-virus vaccination regimens (30 participants per group), or saline placebo (120 participants). H9N2 groups received 2 doses (days 0, 21) of 15µg hemagglutinin (HA) without adjuvant, or 1.9µgHA+AS03A, 1.9µgHA+AS03B, 3.75µgHA+AS03A, or 3...
July 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28719308/a-recombinant-47-kda-outer-membrane-protein-induces-an-immune-response-against-orientia-tsutsugamushi-strain-boryong
#17
Sangho Choi, Hang Jin Jeong, Kyu-Jam Hwang, Byoungchul Gill, Young Ran Ju, Yeong Seon Lee, Jeongmin Lee
We investigated the 47-kDa outer membrane protein (OMP), which is a periplasmic serine protease and an antigenic major surface protein of Orientia tsutsugamushi, as a vaccine candidate. We developed a conventional subunit vaccine expressing recombinant 47-kDa OMP (rec47) and a DNA vaccine (p47). In mouse immunization experiments, intranasal immunization with rec47 alone or with rec47 plus heat-labile enterotoxin B subunit from Escherichia coli or plus cholera toxin (CT) as adjuvants induced a higher amount of rec47-specific antibodies than intramuscular immunization with p47 alone or with p47 plus pBOOST2-samIRF7/3 (pB) as adjuvant...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28719287/phase-1-randomized-study-of-a-tetravalent-dengue-purified-inactivated-vaccine-in-healthy-adults-in-the-united-states
#18
Alexander C Schmidt, Leyi Lin, Luis J Martinez, Richard C Ruck, Kenneth H Eckels, Alix Collard, Rafael De La Barrera, Kristopher M Paolino, Jean-François Toussaint, Edith Lepine, Bruce L Innis, Richard G Jarman, Stephen J Thomas
AbstractThe safety and immunogenicity of four formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV), formulated at 1 or 4 μg with aluminum hydroxide (alum) or at 1 μg with an adjuvant system (AS01E or AS03B), were evaluated in a first-time-in-human, placebo-controlled, randomized, observer-blind, phase 1 trial in the continental United States. Two doses of vaccine or placebo were administered intramuscularly 4 weeks apart to 100 healthy adults 18-39 years of age, randomized 1:1:1:1:1 to receive one of four DPIV formulations or saline placebo...
June 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28716554/calcium-phosphate-nanoparticle-capnp-for-dose-sparing-of-inactivated-whole-virus-pandemic-influenza-a-h1n1-2009-vaccine-in-mice
#19
Tülin Morçӧl, Brett L Hurst, E Bart Tarbet
The emergence of pandemic influenza strains, particularly the reemergence of the swine-derived influenza A (H1N1) in 2009, is reaffirmation that influenza viruses are very adaptable and influenza remains as a significant global public health treat. As recommended by the World Health Organization (WHO), the use of adjuvants is an attractive approach to improve vaccine efficacy and allow dose-sparing during an influenza emergency. In this study, we utilized CaPtivate Pharmaceutical's proprietary calcium phosphate nanoparticles (CaPNP) vaccine adjuvant and delivery platform to formulate an inactivated whole virus influenza A/CA/04/2009 (H1N1pdm) vaccine as a potential dose-sparing strategy...
July 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28715767/non-human-primates-as-a-model-for-understanding-the-mechanism-of-action-of-toll-like-receptor-based-vaccine-adjuvants
#20
REVIEW
Elizabeth A Thompson, Karin Loré
While transgenic mouse models are powerful for understanding how the immune system is manipulated by vaccines, they cannot fully recapitulate the characteristics of the innate immune responses leading to adaptive immunity after vaccination in humans. Outbred non-human primates are far more representative models of human vaccine responses as there is high degree of similarities in immune cell subset distributions, receptor expression (including toll-like receptors; TLRs), and immune cell functions, in addition to modeling doses and injection sites more accurately...
July 14, 2017: Current Opinion in Immunology
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