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aluminum vaccine

Christine Juergens, James Trammel, Yasuko Shoji, Scott Patterson, Wendy Watson, Chris Webber, William C Gruber, Daniel A Scott, Beate Schmoele-Thoma
Injection site reactions (ISRs; redness, swelling and pain) commonly occur within 1-2 days after vaccination. After administration of toxoid vaccines including diphtheria toxoid, a later onset of ISRs has also been observed. As the serotype capsular polysaccharides in the 13-valent pneumococcal conjugate vaccine (PCV13) are conjugated to cross-reactive material 197 (CRM197 ), a nontoxic variant of diphtheria toxin, the onset of ISRs over 14 days was explored in 8 adult studies with 19 cohorts. Subjects received PCV13 with aluminum phosphate (AlPO4 , n = 5667) or without AlPO4 (n = 304); 109 subjects received 23-valent pneumococcal polysaccharide vaccine (PPSV23)...
March 15, 2018: Human Vaccines & Immunotherapeutics
Stephanie Donaldson, Theresa Canavan, Peter G Pavlidakey, Wendy C Cantrell, Boni E Elewski
Local adverse reactions to vaccination are typically mild and often quickly resolve. Vaccine adjuvants such as aluminum salts in combination with improper vaccination technique may result in severe local adverse reactions. As far as we know, there is only one prior case of frankly necrotic rapidly progressing vaccine site necrosis, which occurred in a pediatric patient.1 To our knowledge, this is the first adult case of vaccine site necrosis to be reported. The presumed etiology has been aluminum salt adjuvants and improper vaccination technique...
March 1, 2018: Journal of Drugs in Dermatology: JDD
Ricardo A Orbegozo-Medina, Victoria Martínez-Sernández, Marta González-Warleta, José Antonio Castro-Hermida, Mercedes Mezo, Florencio M Ubeira
Fasciolosis continues to be a major cause of economic losses in the livestock industry and a growing threat to humans. The limited spectrum of effective anthelmintics and the appearance of resistances urge the need for developing an effective vaccine. Most studies have been focused on the use of TH1 -polarizing adjuvants and the use of recombinant Fasciola critical molecules and, despite the efforts, no reproducible protections have been achieved. The F. hepatica MF6p/FhHDM-1 protein is a heme-binding protein also reported to have immunomodulatory properties, constituting a promising target for vaccination and/or as target for the development of new flukicides...
March 8, 2018: Vaccine
María Elena González-Sánchez, Montserrat Cuquerella, José M Alunda
Haemonchus contortus is the most pathogenic gastrointestinal helminth of small ruminants. Natural or experimental repeated infections and several native antigens confer a partially protective immune response but vaccination with subunit antigens has been elusive. Promising results have been obtained with a recombinant form of a somatic antigen (rHc23). In this paper we present the results obtained in vaccination trials in lambs using two dosages of rHc23 and standard adjuvants. Six-months old Manchego females lambs were vaccinated with rHc23 (50 or 200 μg/dose) adjuvanted with 1mL aluminum hydroxide on days -42, -28 and -14 or with 200 μg/dose rHc23 and 5 mg Quil A on days -49, -28 and -7...
2018: PloS One
Jorge Galindo-Villegas, Alicia García-Alcazar, José Meseguer, Victoriano Mulero
A key goal of a successful vaccine formulation is the strong induction of persistent protective immune responses without producing side-effects. Adjuvants have been proved to be successful in several species at inducing increased immune responses against poorly immunogenic antigens. Fish are not the exception and promising results of adjuvanted vaccine formulations in many species are needed. In this study, over a period of 300 days, we characterized the apparent damage and immune response in gilthead seabream immunized by intraperitoneal injection with the model antigen keyhole limpet hemocyanin (KLH) alone or formulated with Montanide ISA water-in-oil (761 or 763), or Imject™ aluminum hydroxide (aluminium), as adjuvants...
March 3, 2018: Fish & Shellfish Immunology
M Ghalavand, M Saadati, A Ahmadi, E Abbasi, J Salimian
OBJECTIVES: The present study was aimed at comparing tetanus toxoid (TT)‑loaded-chitosan nanoparticles with aluminum hydroxide as a common vaccine adjuvant. BACKGROUND: Tetanus remains to be a major public health problem. Nanoparticles have been extensively used as immune adjuvants. Tetanus toxoid (TT) encapsulated in chitosan nanoparticles is considered to be a promising tetanus vaccine candidate. METHODS: TT‑loaded chitosan nanoparticles were prepared by the ionic gelation method...
2018: Bratislavské Lekárske Listy
Sachin S Shivatare, Vidya S Shivatare, Chung-Yi Wu, Chi-Huey Wong
We present a highly efficient way for the rapid preparation of a wide range of N-linked oligosaccharides (estimated to exceed 20,000 structures) that are commonly found on human glycoproteins. To achieve the desired structural diversity, the strategy began with the chemo-enzymatic synthesis of three kinds of oligosaccharyl fluoride modules, followed by their stepwise α-selective glycosylations at the 3-O and 6-O positions of the mannose residue of the common core trisaccharide having a crucial β-mannoside linkage...
February 5, 2018: Journal of Visualized Experiments: JoVE
Zoltan Beck, Oscar B Torres, Gary R Matyas, David E Lanar, Carl R Alving
Aluminum salts have been used as vaccine adjuvants for >50 years, and they are currently present in at least 146 licensed vaccines worldwide. In this study we examined whether adsorption of Army Liposome Formulation (ALF) to an aluminum salt that already has an antigen adsorbed to it might result in improved immune potency of the aluminum-adsorbed antigen. ALF is composed of a family of anionic liposome-based adjuvants, in which the liposomes contain synthetic phospholipids having dimyristoyl fatty acyl groups, cholesterol and monophosphoryl lipid A (MPLA)...
February 9, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Padma Malyala, Donatello Laera, Simona Cianetti, Simone Bufali, Marianna Aggravi, Elvira Ianni, Casey Judge, Gillis Otten, Manmohan Singh, Derek T O' Hagan
Adjuvants are necessary to enable vaccine development against a significant number of challenging pathogens for which effective vaccines are not available [1]. We engineered a novel small-molecule immune potentiator (SMIP), a benzonaphthyridine agonist targeting toll-like receptor 7 (TLR7), as a vaccine adjuvant. TLR7 agonist (TLR7a) was engineered to be adsorbed onto aluminum hydroxide (AlOH), and the resulting AlOH/TLR7a was evaluated as a vaccine adjuvant [2-6]. AlOH/TLR7a exploits the flexibility of AlOH formulations, has an application in many vaccine candidates, and induced good efficacy and safety profiles against all tested antigens (bacterial- and viral-derived protein antigens, toxoids, glycoconjugates, etc...
February 5, 2018: Journal of Pharmaceutical Sciences
Xiaoli Zhang, Feng Yang, Jintao Zou, Weiru Wu, Haiming Jing, Qiang Gou, Haibo Li, Jiang Gu, Quanming Zou, Jinyong Zhang
Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of severe nosocomial and community acquired infections, these infections are major health problems for cystic fibrosis patients and immune-compromised individuals. The emergence of multidrug-resistant isolates highlights the need to develop alternative strategies for treatment of P. aeruginosa infections. Outer membrane vesicles (OMVs) are spherical nanometer-sized proteolipids that are secreted from numerous of pathogenic Gram-negative bacteria, and a number of studies have confirmed the protective efficacy for use of OMVs as candidate vaccines...
February 14, 2018: Vaccine
Jiri Beran, Jason D Lickliter, Tino F Schwarz, Casey Johnson, Laurence Chu, Joseph B Domachowske, Pierre Van Damme, Kanchanamala Withanage, Laurence A Fissette, Marie-Pierre David, Koen Maleux, Alexander C Schmidt, Marta Picciolato, Ilse Dieussaert
Background: Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost pre-existing neutralizing antibody titers, providing passive protection to newborns. Methods: Two observer-blind, controlled studies (RSV F-020 [NCT02360475], RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, non-pregnant 18-45-year-old women. Both studies used licensed Tdap vaccine as control...
February 1, 2018: Journal of Infectious Diseases
Hao Jiang, Qin Wang, Lin Li, Qin Zeng, Hanmei Li, Tao Gong, Zhirong Zhang, Xun Sun
Due to its safety and efficacy, aluminum hydroxide is used as an immune adjuvant in human vaccines for over 80 years. Being a Th2 stimulator, the classical gel-like adjuvant, however, fails to generate CD8+ T cell responses, which are important for cancer vaccines. Here, aluminum hydroxide is turned from gel into nano-sized vaccine carriers AlO(OH)-polymer nanoparticles (APNs) to promote their lymphatic migration. After actively uptaken via scavenger receptor-A by antigen-presenting cells (APCs) resident in lymph nodes (LNs), APNs destabilize lysosomes resulting in efficient cytosolic delivery and cross-presentation of antigens...
January 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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
Patrick L Ahl, Sheng-Ching Wang, Ramesh Chintala, Christopher D Mensch, William J Smith, Marc Wenger, Jeffrey T Blue
Aluminum containing adjuvants have been widely used in vaccine formulations to safely and effectively potentiate the immune response. The examination of the extent of antigen adsorption to aluminum adjuvant is always evaluated during the development of aluminum adjuvant containing vaccines. A rapid automated high throughput assay was developed to measure antigen adsorption in a 96-well plate format using a TECAN Freedom EVO® (TECAN). The antigen adsorption levels at a constant adjuvant concentration for each sample were accurately measured at 12 antigen /adjuvant (w/w) formulation ratios...
January 17, 2018: PDA Journal of Pharmaceutical Science and Technology
Juliette Fortpied, Florence Wauters, Christelle Rochart, Philippe Hermand, Bernard Hoet, Nicolas Moniotte, Ivo Vojtek
Accidental exposure of a vaccine containing an aluminum-salt adjuvant to temperatures below 0°C in the cold chain can lead to freeze damage. Our study evaluated the potential for freeze damage in a licensed aluminum-salt-containing protein-D-conjugated pneumococcal vaccine (PHiD-CV; Synflorix, GSK) in conditions that included static storage, single subzero-temperature excursions, and simulated air-freight transportation. Several parameters were assessed including freezing at subzero temperatures, aluminum-salt-particle size, antigen integrity and immunogenicity in the mouse...
January 16, 2018: Human Vaccines & Immunotherapeutics
Sachin G Thakkar, Haiyue Xu, Xu Li, Zhengrong Cui
In an effort to improve the adjuvanticity of insoluble aluminum salts, we discovered that the adjuvant activity of aluminum salt nanoparticles is significantly stronger than aluminum salt microparticles, likely related to nanoparticle's stronger ability to directly activate NLRP3 inflammasome as the nanoparticles are more efficiently taken up by phagocytic cells. Endogenous signals such as uric acid from cell damage or death caused by the cytotoxicity of aluminum salts are thought to indirectly activate inflammasome, prompting us to hypothesize that the potent adjuvant activity of aluminum salt nanoparticles is also related to their ability to stimulate uric acid production...
January 15, 2018: Journal of Drug Targeting
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
Samantha C Gordon, Diana W Bartenstein, Shahein H Tajmir, Johanna S Song, Elena B Hawryluk
A 3-year-old girl presented with a 7-month history of a waxing and waning left thigh mass associated with pruritus and erythema at the site of two previous DTaP-HepB-IPV vaccinations. Patch testing was positive to aluminum chloride, supporting a diagnosis of vaccine granuloma secondary to aluminum allergy; her symptoms had been well controlled with antihistamines and topical steroids. Injection site granulomas are a benign but potentially bothersome reaction to aluminum-containing immunizations that can be supportively managed, and we encourage strict adherence to the recommended vaccine schedule in this setting...
January 4, 2018: Pediatric Dermatology
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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