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Alum adjuvant

Hui Liu, Zhenghu Jia, Chengmao Yang, Mei Song, Zhe Jing, Yapu Zhao, Zhenzhou Wu, Liqing Zhao, Dongsheng Wei, Zhinan Yin, Zhangyong Hong
Aluminum salt (Alum) is one of the most important immune adjuvants approved for use in humans, however it is not suitable for vaccination against various chronic infectious diseases and cancers for not being able to induce cell-mediated (Th1) immunity. Here, we encapsulated an Alum colloid inside β-glucan particles (GPs), which are a type of natural particles derived from the yeast glucan shells, to prepare hybrid GP-Alum (GP-Al) adjuvant particles with a very uniform size of 2-4 μm. These hybrid particles can be used to load antigen proteins through a simple mixing procedure, and can be highly specifically targeted to antigen-presenting cells (APCs) and strongly activate dendritic cells (DCs) maturation and cytokine secretion...
March 12, 2018: Biomaterials
Laura Aragoneses-Fenoll, Gloria Ojeda, María Montes-Casado, Yeny Acosta-Ampudia, Umberto Dianzani, Pilar Portolés, José M Rojo
Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110α conditionally deleted in CD4+ and CD8+ T lymphocytes (p110α-/- ΔT) were used. p110α-/- ΔT mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen...
2018: Frontiers in Immunology
Jamie Jennings-Gee, Sally Quataert, Tridib Ganguly, Ralph D'Agostino, Rajendar Deora, Purnima Dubey
The reemergence of pertussis or whooping cough in several countries highlights the need for better vaccines. Acellular pertussis vaccines (aPV) contain alum as the adjuvant and elicit Th2 biased immune responses that are less effective in protecting against infection than the reactogenic whole cell pertussis vaccines (wPV), which elicit primarily a Th1/Th17 response. An important goal for the field is to devise aPVs that will induce immune responses similar to wPV. We show that Bordetella Colonization Factor A (BcfA), an outer membrane protein from B...
March 12, 2018: Infection and Immunity
Clemente Diaz, Leyi Lin, Luis J Martinez, Kenneth H Eckels, Maribel Campos, Richard G Jarman, Rafael De La Barrera, Edith Lepine, Jean-François Toussaint, Irma Febo, Bruce L Innis, Stephen J Thomas, Alexander C Schmidt
The safety and immunogenicity of four adjuvanted formulations of an investigational tetravalent dengue purified inactivated vaccine (DPIV) were evaluated in a predominantly dengue-primed population in Puerto Rico. In this placebo-controlled, randomized, observer-blind, phase I trial, 100 healthy adults were randomized 1:1:1:1:1 to receive DPIV at Day (D)0 and D28 (1 μg per dengue virus [DENV] type 1-4 adjuvanted with either alum, AS01E or AS03B , or 4 μg per DENV type adjuvanted with alum) or saline placebo...
March 5, 2018: American Journal of Tropical Medicine and Hygiene
Amjad Islam Aqib, Aftab Ahmad Anjum, Muhammad Ijaz, Riaz Hussain, Rais Ahmed, Shahid Hussain Farooqi, Hassan Bin Aslam, Kashif Hussain, Khalid Mehmood, Hui Zhang
The predominant Staphylococcus aureus (S. aureus), an etiological agent of camel mastitis is becoming drug resistant that invites prevention and control strategies. Vaccine production would have a valuable impact on public health. Therefore, in present study inactivated vaccine with different adjuvants was prepared and evaluated against S. aureus. The vaccinal isolate recovered from camel subclinical mastitis was coagulase positive (PCR based), having expressed pseudocapsule, holding alpha-beta hemolysin characteristics, and multiple drug resistant...
March 3, 2018: Microbial Pathogenesis
Eveline M Boerhout, Ad P Koets, Tanja G T Mols-Vorstermans, Piet J M Nuijten, Mathieu J H Hoeijmakers, Victor P M G Rutten, Jetta J E Bijlsma
Intramammary infections in cattle resulting in mastitis have detrimental effects on cows' well-being, lifespan and milk production. In the host defense against S. aureus mastitis antibodies are thought to play an important role. To explore potential ways to increase antibody titers in the bovine mammary gland the effects of various adjuvants on the magnitude, isotype, and neutralizing capacity of antibodies produced following subcutaneous vaccine administration at different immunization sites were analyzed...
March 1, 2018: Veterinary Research
Candy S Hwang, Paul T Bremer, Cody J Wenthur, Sam On Ho, SuMing Chiang, Beverly Ellis, Bin Zhou, Gary Fujii, Kim D Janda
In recent years, drug conjugate vaccines have shown promise as therapeutics for substance use disorder. As a means to improve the efficacy of a heroin conjugate vaccine, we systematically explored twenty vaccine formulations with varying combinations of carrier proteins and adjuvants. In regard to adjuvants, we explored a Toll-like receptor 9 (TLR9) agonist and a TLR3 agonist in the presence of alum. The TLR9 agonist was cytosine-guanine oligodeoxynucleotide 1826 (CpG ODN 1826), while the TLR3 agonist was virus-derived genomic doubled-stranded RNA (dsRNA)...
February 8, 2018: Molecular Pharmaceutics
Min-Yuan Chia, Wan-Yu Chung, Chun-Hsiung Wang, Wei-Hau Chang, Min-Shi Lee
Although Enterovirus 71 (EV71) has only one serotype based on serum neutralization tests using hyperimmune animal antisera, three major genogroups (A, B and C) including eleven genotypes (A, B1-B2, and C1-C5) can be well classified based on phylogenetic analysis. Since 1997, large-scale EV71 epidemics occurred cyclically with different genotypes in the Asia-Pacific region. Therefore, development of EV71 vaccines is a national priority in several Asian countries. Currently, five vaccine candidates have been evaluated in clinical trials in China (three C4 candidates), Singapore (one B2 candidate), and Taiwan (one B4 candidate)...
February 2, 2018: Vaccine
Amanda Fernandes Pinheiro, Bárbara Couto Roloff, Angelita da Silveira Moreira, Maria Elisabeth Aires Berne, Renato Andreotti Silva, Fábio Pereira Leivas Leite
The parasite Neospora caninum is the main cause of abortion in cattle in many countries around the world, so a vaccine is a rational approach method for the control of the disease. An effective vaccine should be able to prevent both, the horizontal and vertical transmission of N. caninum. In this study, the immune vaccinal response of the recombinant protein rNcSRS2 of N. caninum expressed in Pichia pastoris and formulated with water-in-oil emulsion, xanthan gum, and alum hydroxide was assessed in an experimental murine model...
January 23, 2018: Vaccine
Stéphane Pillet, Éric Aubin, Sonia Trépanier, Jean-François Poulin, Bader Yassine-Diab, Jan Ter Meulen, Brian J Ward, Nathalie Landry
The hemagglutinination inhibition (HI) response remains the gold standard used for the licensure of influenza vaccines. However, cell-mediated immunity (CMI) deserves more attention, especially when evaluating H5N1 influenza vaccines that tend to induce poor HI response. In this study, we measured the humoral response (HI) and CMI (flow cytometry) during a Phase II dose-ranging clinical trial (NCT01991561). Subjects received two intramuscular doses, 21 days apart, of plant-derived virus-like particles (VLP) presenting the A/Indonesia/05/2005 H5N1 influenza hemagglutinin protein (H5) at the surface of the VLP (H5VLP)...
2018: NPJ Vaccines
Jie Luo, Jon Lindstrom
Experimental autoimmune myasthenia gravis (EAMG) and myasthenia gravis (MG) are caused by autoantibodies to the extracellular domain of muscle nicotinic acetylcholine receptors (AChRs). Autoantibodies to the cytoplasmic domain of AChRs do not cause EAMG because they cannot bind AChRs in vivo. The ideal MG therapy would quickly and permanently suppress only the pathological autoimmune response to AChRs. We have developed a specific immunosuppressive therapy for EAMG that involves immunizing rats with bacterially expressed cytoplasmic domains of human muscle AChRs...
January 29, 2018: Annals of the New York Academy of Sciences
Ailian Zhang, Xiumei Yang, Quanxiao Li, Yu Yang, Gan Zhao, Bin Wang, Daocheng Wu
A safe and effective vaccine adjuvant is important in modern vaccines. Various Chinese herbal polysaccharides can activate the immune system. Cistanche deserticola (CD) is a traditional Chinese herb and an adjuvant candidate. Here, we confirmed that water-extractable polysaccharides of CD (WPCD) could modulate immune responses in vitro and in vivo. In a dose-dependent manner, WPCD significantly promoted the maturation and function of murine marrow-derived dendritic cells (BM-DCs) through up-regulating the expression levels of MHC-II, CD86, CD80, and CD40, allogenic T cell proliferation, and the yields of IL-12 and TNF-α via toll-like receptor4 (TLR4), as indicated by in vitro experiments...
2018: PloS One
Erman Tritama, Catur Riani, Indra Rudiansyah, Arip Hidayat, Siti Azizah Kharisnaeni, Debbie Sofie Retnoningrum
The function of adjuvant in maintaining the long-term immune response to Typhoid conjugate vaccine (TCV) was evaluated in. Two TCV products, Vi-DT and Vi-TT, were formulated in either aluminum phosphate (AlPO4) or aluminum hydroxide (AlOH) as adjuvants and TCV formulated in phosphate buffer saline were used as controls. In each case, a group of Balb/c mice was injected intramuscularly with two doses of the formulated vaccine at two-week intervals. The anti-Vi IgG responses were monitored by Enzyme-Linked Immunosorbent Assay and the levels of CD4+ T-cells expressing cytokine were characterized using intracellular cytokine staining...
January 23, 2018: Human Vaccines & Immunotherapeutics
Himani Garg, Jagdish C Gupta, G P Talwar, Shweta Dubey
Survivin has received attention as a potential target for cancer immunotherapy because of its crucial role in oncogenesis. We undertook this study to evaluate the immunotherapeutic potential of combination of recombinant Survivin along with adjuvant alum and immune modulator Mycobacterium indicus pranii (MIP). In vivo efficacy of the combination was studied in an invasive murine breast cancer model. Recombinant Survivin protein was purified from E. coli based expression system and characterized by western blotting...
January 22, 2018: Preparative Biochemistry & Biotechnology
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
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
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
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
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
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
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