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Alum adjuvant

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https://www.readbyqxmd.com/read/29349774/the-vaccine-adjuvant-alum-promotes-il-10-production-that-suppresses-th1-responses
#1
Ewa Oleszycka, Sean McCluskey, Fiona A Sharp, Natalia Muñoz-Wolf, Emily Hams, Aoife L Gorman, Padraic G Fallon, Ed C Lavelle
The effectiveness of many vaccines licensed for clinical use relates to the induction of neutralising antibodies, facilitated by the inclusion of vaccine adjuvants, particularly alum. However, the ability of alum to preferentially promote humoral rather than cellular, particularly Th1-type responses, is not well understood. We demonstrate that alum activates immunosuppressive mechanisms following vaccination, which limit its capacity to induce Th1 responses. One of the key cytokines limiting excessive immune responses is IL-10...
January 19, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29330512/inactivated-rotavirus-vaccine-by-parenteral-administration-induces-mucosal-immunity-in-mice
#2
Theresa K Resch, Yuhuan Wang, Sung-Sil Moon, Jessica Joyce, Song Li, Mark Prausnitz, Baoming Jiang
To improve the safety and efficacy of oral rotavirus vaccines, we developed an inactivated rotavirus vaccine (IRV) for parenteral administration. Since it remains unknown whether parenteral vaccination can induce mucosal immunity, we performed a comprehensive assessment of immune responses to IRV in mice with an adjuvant-free dissolving polymer MN patch or by alum-adjuvanted IM injection. We demonstrated that IRV induced the expression of the gut homing receptor LPAM-1 on T and B cells in spleen and mLN of vaccinated mice...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29328884/evaluation-of-g2-citric-acid-based-dendrimer-as-an-adjuvant-in-veterinary-rabies-vaccine
#3
Vahid Asgary, Alireza Shoari, Majid Afshar Moayad, Mehdi Shafiee Ardestani, Razieh Bigdeli, Leila Ghazizadeh, Mohammad Sadeq Khosravy, Erfan Panahnejad, Alireza Janani, Rouzbeh Bashar, Maliheh Abedi, Reza Ahangari Cohan
For induction of an appropriate immune response, especially in the case of an inactivated vaccine, the use of an adjuvant is crucial. In this study, adjuvanticity effect of G2 dendrimer in veterinary rabies vaccine has been investigated. A nonlinear globular G2 dendrimer comprising citric acid and polyethylene glycol 600 (PEG-600) was synthesized and the toxicity was studied in vitro on the J774A.1 cell line. The adjuvanticity effect of the dendrimer was then investigated on rabies virus in NMRI mice as a model...
January 2018: Viral Immunology
https://www.readbyqxmd.com/read/29317357/novel-identified-aluminum-hydroxide-induced-pathways-proof-monocyte-activation-and-pro-inflammatory-preparedness
#4
Sietske Kooijman, Jolanda Brummelman, Cécile A C M van Els, Fabio Marino, Albert J R Heck, Geert P M Mommen, Bernard Metz, Gideon F A Kersten, Jeroen L A Pennings, Hugo D Meiring
Aluminum-based adjuvants are the most widely used adjuvants in human vaccines. A comprehensive understanding of the mechanism of action of aluminum adjuvants at the molecular level, however, is still elusive. Here, we unravel the effects of aluminum hydroxide Al(OH)3 by a systems-wide analysis of the Al(OH)3-induced monocyte response. Cell response analysis by cytokine release was combined with (targeted) transcriptome and full proteome analysis. Results from this comprehensive study revealed two novel pathways to become activated upon monocyte stimulation with Al(OH)3: the first pathway was IFNβ signaling possibly induced by DAMP sensing pathways like TLR or NOD1 activation, and second the HLA class I antigen processing and presentation pathway...
January 6, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29315762/effect-of-apoptosis-associated-speck-like-protein-containing-a-caspase-recruitment-domain-on-vaccine-efficacy-overcoming-the-effects-of-its-deficiency-with-aluminum-hydroxide-adjuvant
#5
Deuk-Ki Lee, Eun-Young Lee, Ryoon-Ho Kim, Hye-Won Kwak, Joo Young Kim, Hun Kim, Kyung-Won Kang, Sang-Myeong Lee, Jong-Hwan Park, Jun Chang, Jae-Hwan Nam
Host factors such as nutritional status and immune cell state are important for vaccine efficacy. Inflammasome activation may be important for triggering vaccine-induced humoral and cell-mediated immune responses. Formulations with alum as a typical adjuvant to overcome the effects of host factors have recently been shown to induce inflammasome activation, which augments vaccine efficacy. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is one of main components of inflammasomes, but it is not clear whether ASC affects the vaccine-induced immune response...
January 8, 2018: Microbiology and Immunology
https://www.readbyqxmd.com/read/29296883/innate-transcriptional-effects-by-adjuvants-on-the-magnitude-quality-and-durability-of-hiv-envelope-responses-in-nhps
#6
Joseph R Francica, Daniel E Zak, Caitlyn Linde, Emilio Siena, Carrie Johnson, Michal Juraska, Nicole L Yates, Bronwyn Gunn, Ennio De Gregorio, Barbara J Flynn, Nicholas M Valiante, Padma Malyala, Susan W Barnett, Pampi Sarkar, Manmohan Singh, Siddhartha Jain, Margaret Ackerman, Munir Alam, Guido Ferrari, Georgia D Tomaras, Derek T O'Hagan, Alan Aderem, Galit Alter, Robert A Seder
Adjuvants have a critical role for improving vaccine efficacy against many pathogens, including HIV. Here, using transcriptional RNA profiling and systems serology, we assessed how distinct innate pathways altered HIV-specific antibody responses in nonhuman primates (NHPs) using 8 clinically based adjuvants. NHPs were immunized with a glycoprotein 140 HIV envelope protein (Env) and insoluble aluminum salts (alum), MF59, or adjuvant nanoemulsion (ANE) coformulated with or without Toll-like receptor 4 (TLR4) and 7 agonists...
November 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29289383/immunogenicity-of-a-two-dose-investigational-hepatitis-b-vaccine-hbsag-1018-using-a-toll-like-receptor-9-agonist-adjuvant-compared-with-a-licensed-hepatitis-b-vaccine-in-adults
#7
Sam Jackson, Joseph Lentino, James Kopp, Linda Murray, William Ellison, Margaret Rhee, Gerald Shockey, Lalith Akella, Kimberly Erby, William L Heyward, Robert S Janssen
BACKGROUND: Hepatitis B virus infection remains an important public health problem in the United States. Currently approved alum-adjuvanted vaccines require three doses and have reduced immunogenicity in adults, particularly in those who have diabetes mellitus, or are older, male, obese, or who smoke. METHODS: Phase 3 observer-blinded, randomized (2:1 HBsAg-1018 [HEPLISAV-B™]:HBsAg-Eng [Engerix-B®]), active-controlled trial in adults 18-70 years of age. HBsAg-1018 was administered intramuscularly at weeks 0 and 4 and placebo at week 24 and HBsAg-Eng at weeks 0, 4, and 24...
December 27, 2017: Vaccine
https://www.readbyqxmd.com/read/29232151/adjuvanted-influenza-vaccines
#8
John S Tregoning, Ryan F Russell, Ekaterina Kinnear
In spite of current influenza vaccines being immunogenic, evolution of the influenza virus can reduce efficacy and so influenza remains a major threat to public health. One approach to improve influenza vaccines is to include adjuvants; substances that boost the immune response. Adjuvants are particularly beneficial for influenza vaccines administered during a pandemic when a rapid response is required or for use in patients with impaired immune responses, such as infants and the elderly. This review outlines the current use of adjuvants in human influenza vaccines, including what they are, why they are used and what is known of their mechanism of action...
December 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29209310/alum-activates-the-bovine-nlrp3-inflammasome
#9
Ciaran Harte, Aoife L Gorman, S McCluskey, Michael Carty, Andrew G Bowie, C J Scott, Kieran G Meade, Ed C Lavelle
There has been a move away from vaccines composed of whole or inactivated antigens toward subunit-based vaccines, which although safe, provide less immunological protection. As a result, the use of adjuvants to enhance and direct adaptive immune responses has become the focus of much targeted bovine vaccine research. However, the mechanisms by which adjuvants work to enhance immunological protection in many cases remains unclear, although this knowledge is critical to the rational design of effective next generation vaccines...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29196724/hierarchically-porous-and-cu-and-zn-containing-%C3%AE-alooh-mesostrands-as-adjuvants-for-cancer-immunotherapy
#10
Xia Li, Mohamed A Shenashen, Xiupeng Wang, Atsuo Ito, Akiyoshi Taniguchi, Sherif A Ei-Safty
Alum is the only licensed adjuvant by Food and Drug Administration of USA used in many human vaccines and has excellent safety record in clinical applications. However, alum hardly induces T helper 1 (Th1) immune responses that are required for anti-tumor immunity. In the present study, we fabricated hierarchical copper- and zinc- buds dressing γ-AlOOH mesostrands (Cu- and Zn-AMSs) with randomly wrinkled morphology, mesoscale void- or cave-like pockets, high-exposed surface coverage sites, and positive charge streams in saline...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29194575/the-adjuvant-system-as01-upregulates-neutrophil-cd14-expression-and-neutrophil-associated-antigen-transport-in-the-local-lymphatic-network
#11
Melanie R Neeland, Wei Shi, Catherine Collignon, Els N T Meeusen, Arnaud M Didierlaurent, Michael J de Veer
The liposome-based Adjuvant System AS01 is under evaluation for use in several vaccines in clinical development. We have previously shown that AS01 injected with hepatitis B surface antigen (HBsAg) induces a distinct cellular signature within the draining lymphatics that enhances local lymphocyte recruitment and antigen-specific humoral immunity. Here, we show that AS01-induced neutrophil recruitment is associated with increased expression of CD14 and enhanced antigen uptake capacity in neutrophils from both afferent and efferent lymphatic compartments in the first 48h after vaccination...
December 1, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/29192493/biodegradable-metal-ions-doped-mesoporous-silica-nanospheres-stimulate-anti-cancer-th1-immune-response-in-vivo
#12
Xiupeng Wang, Xia Li, Atsuo Ito, Yu Sogo, Yohei Watanabe, Noriko Tsuji, Tadao Ohno
Modern vaccines usually require accompanying adjuvants to increase the immune response to antigens. Aluminum compounds (alum) are the most commonly used adjuvants in human vaccinations for infection diseases. However, alum adjuvants are non-degradable, cause side effects due to the persistence of alum at injection sites, and are rather ineffective for cancer immunotherapy, which requires the Th1 immune response. Recently, we have shown that a plain mesoporous silica (MS) adjuvant can stimulate Th1 anti-cancer immunity for cancer vaccines...
December 1, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29179131/engineering-detoxified-pneumococcal-pneumolysin-derivative-%C3%AE-a146ply-for-self-biomineralization-of-calcium-phosphate-assessment-of-their-protective-efficacy-in-murine-infection-models
#13
Jingwen Wu, Kaifeng Wu, Wenchun Xu, Taixian Yuan, Xiaofang Wang, Jinghui Zhang, Yajun Min, Yibing Yin, Xuemei Zhang
Vaccine design ushered in the era of nanotechnology, as the vaccine is being developed toward particulate formulation. We have previously shown that the attenuated pneumolysin mutant (ΔA146PLY) was a safe and effective pneumococcal vaccine candidate. Here, to further optimize the formulation, we fused calcium phosphate (CaP) binding domains with ΔA146PLY so that the biocompatible CaP can mineralize with the protein automatically, allowing simple production of nanoparticle antigen during preparation. We fabricated four different nanoparticles, and then we compared the characteristics of different CaP-ΔA146PLY nanoparticles and demonstrated the influence of CaP binding domains on the size, shape and surface calcium content of the nanoparticles...
November 20, 2017: Biomaterials
https://www.readbyqxmd.com/read/29147873/comparison-of-the-adjuvanticity-of-two-adjuvant-formulations-containing-de-o-acylated-lipooligosaccharide-on-japanese-encephalitis-vaccine-in-mice
#14
Ara Ko, Seo Ri Wui, Ji In Ryu, Hien Thi Thu Do, Yeon Jeong Lee, Soo Jeong Lim, Inmoo Rhee, Dae Im Jung, Jin-Ah Park, Jung-Ah Choi, Man Ki Song, Na Gyong Lee
Adjuvants are essential vaccine components used to enhance, accelerate, and/or prolong adaptive immunity against specific vaccine antigens. In this study, we compared the adjuvanticity of two adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS), a toll-like receptor 4 agonist, on the Japanese encephalitis (JE) vaccine in mice. Mice were immunized once or twice at a two-week interval with inactivated JE vaccine in the absence or presence of adjuvant. We found that both the alum- and the liposome-based formulation induced significantly faster and higher serum IgG antibody responses as compared with the non-adjuvanted vaccine after either one or two immunizations...
November 17, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29089195/superior-immunogenicity-of-hcv-envelope-glycoproteins-when-adjuvanted-with-cyclic-di-amp-a-sting-activator-or-archaeosomes
#15
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/29079105/immunization-against-full-length-protein-and-peptides-from-the-lutzomyia-longipalpis-sand-fly-salivary-component-maxadilan-protects-against-leishmania-major-infection-in-a-murine-model
#16
William H Wheat, Erik N Arthun, John S Spencer, Daniel P Regan, Richard G Titus, Steven W Dow
Leishmaniasis is an arthropod vectored disease causing considerable human morbidity and mortality. Vaccination remains the most realistic and practical means to interrupt the growing number and diversity of sand fly vectors and reservoirs of Leishmania. Since transmission of Leishmania is achieved exclusively by sand fly vectors via immune-modulating salivary substances, conventional vaccination requiring an unmodified host immune response for success are potentially destined to fail unless immunomodulatory factors are somehow neutralized...
October 24, 2017: Vaccine
https://www.readbyqxmd.com/read/29073215/toxoplasma-gondii-serine-protease-inhibitor-1-a-new-adjuvant-candidate-for-asthma-therapy
#17
Ariadna S Soto, Ignacio M Fenoy, Vanesa R Sanchez, Florencia March, Matías D Perrone Sibilia, María de Los Angeles Aldirico, Mariano S Picchio, Nadia Arcon, Patricio L Acosta, Fernando P Polack, Valentina Martin, Alejandra Goldman
Serine-proteases are important players in the pathogenesis of asthma, promoting inflammation and tissue remodeling. It's also known that many serine protease inhibitors display immunomodulatory properties. TgPI-1 is a Toxoplasma gondii protein that exhibits broad spectrum inhibitory activity against serine proteases. In view of the increased prevalence of atopic disorders and the need to develop new treatment strategies we sought to investigate the potential of TgPI-1 for treating respiratory allergies. For this purpose, we developed a therapeutic experimental model...
2017: PloS One
https://www.readbyqxmd.com/read/29073183/adjuvants-and-the-vaccine-response-to-the-ds-cav1-stabilized-fusion-glycoprotein-of-respiratory-syncytial-virus
#18
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/29067316/active-a%C3%AE-immunotherapy-cad106-in-alzheimer-s-disease-a-phase-2b-study
#19
Rik Vandenberghe, Marie-Emmanuelle Riviere, Angelika Caputo, Judit Sovago, R Paul Maguire, Martin Farlow, Giovanni Marotta, Raquel Sanchez-Valle, Philip Scheltens, J Michael Ryan, Ana Graf
INTRODUCTION: This randomized, double-blind, placebo-controlled, 90-week study assessed safety, tolerability, and immunogenicity of CAD106 with/without adjuvant in patients with mild Alzheimer's disease. METHODS: One hundred twenty-one patients received up to seven intramuscular injections of CAD106 (150 μg or 450 μg) or placebo ± adjuvant over 60 weeks. An amyloid positron emission tomography (PET) substudy was also conducted. RESULTS: CAD106 induced strong serological responses (amyloid-beta [Aβ]-Immunoglobuline G[IgG]) in 55...
January 2017: Alzheimer's & Dementia: Translational Research & Clinical Interventions
https://www.readbyqxmd.com/read/29052227/adjuvant-pretreatment-with-alum-protects-neonatal-mice-in-sepsis-through-myeloid-cell-activation
#20
Jaimar C Rincon, Angela L Cuenca, Steven L Raymond, Brittany Mathias, Dina C Nacionales, Ricardo Ungaro, Philip A Efron, James L Wynn, Lyle L Moldawer, Shawn D Larson
The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Especially in the premature neonate where outcomes from sepsis are so dismal, pretreatment strategies to prevent sepsis have received inadequate consideration. Aluminum-based adjuvants (alum) are currently used in many pediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pre-treatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis...
October 20, 2017: Clinical and Experimental Immunology
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