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Aluminum adjuvant vaccine hydroxide

Yunier Rodríguez-Álvarez, Yanelys Morera-Díaz, Haydee Gerónimo-Pérez, Jorge Castro-Velazco, Rafael Martínez-Castillo, Pedro Puente-Pérez, Vladimir Besada-Pérez, Eugenio Hardy-Rando, Araceli Chico-Capote, Klaudia Martínez-Cordovez, Alicia Santos-Savio
BACKGROUND: Interleukin-15 is an immunostimulatory cytokine overexpressed in several autoimmune and inflammatory diseases such as Rheumatoid Arthritis, psoriasis and ulcerative colitis; thus, inhibition of IL-15-induced signaling could be clinically beneficial in these disorders. Our approach to neutralize IL-15 consisted in active immunization with structurally modified human IL-15 (mhIL-15) with the aim to induce neutralizing antibodies against native IL-15. In the present study, we characterized the antibody response in Macaca fascicularis, non-human primates that were immunized with a vaccine candidate containing mhIL-15 in Aluminum hydroxide (Alum), Montanide and Incomplete Freund's Adjuvant...
September 26, 2016: BMC Immunology
Yousef Amini, Bagher Moradi, Mahdi Fasihi-Ramandi
Many materials such as aluminum hydroxide have been tried as adjuvants to compensate low inherent immunogenicity of subunit vaccines. The aim of this study was to evaluate the specific immune response following the administration of aluminum hydroxide nanoparticles with EsxV antigen. The physiochemical properties of the nanoparticle were characterized in vitro. After subcutaneous immunization, cytokine secretion patterns including IFN-gama,IL-4, and TGF-beta levels were measured by indirect enzyme linked immunosorbent assay (ELISA)...
September 20, 2016: Artificial Cells, Nanomedicine, and Biotechnology
Trong Lan Phan, Vinh Thang Ho, Minh Huong Vu, Tuyet Nga Nguyen, Huu Thai Duong, Renee Holt, Rahnuma Wahid, John Donnelly, Jorge Flores
We tested an inactivated egg-grown whole virus influenza A/H5N1 vaccine candidate developed by the Institute of Vaccines and Medical Biologicals (IVAC), a state-run vaccine manufacturer in Vietnam, in a Phase 1, placebo controlled, double blinded, randomized trial. The vaccine was adjuvanted with aluminum hydroxide. The trial enrolled 75 subjects who were randomized to receive two injections of one of the following: low-dose of vaccine (7.5 mcg HA), high-dose of vaccine (15 mcg HA), or placebo. The vaccine candidate was well tolerated with minimal local reactogenicity consisting of mild, short-lived injection site pain and/or tenderness...
October 26, 2016: Vaccine
Jennifer Palomo, Beatris Mastelic-Gavillet, Estelle Woldt, Sabina Troccaz, Emiliana Rodriguez, Gaby Palmer, Claire-Anne Siegrist, Cem Gabay
Human and mouse neonates exhibit limited vaccine responses characterized by predominant Th2 and limited Th1 responses. Because IL-36 exerts a synergic adjuvant effect with IL-12, enhancing Th1 polarization in adult (AD) mice, we administered IL-36β to neonatal (1-wk old) and AD control mice at the time of immunization with tetanus toxoid adsorbed to aluminum hydroxide (TT/Alum). Unexpectedly, the combination of IL-36β with TT/Alum, which was well tolerated in AD mice, proved toxic and even lethal in neonates...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Sodiomon B Sirima, Benjamin Mordmüller, Paul Milligan, Ulysse Ateba Ngoa, Fred Kironde, Frank Atuguba, Alfred B Tiono, Saadou Issifou, Mark Kaddumukasa, Oscar Bangre, Clare Flach, Michael Christiansen, Peter Bang, Roma Chilengi, Søren Jepsen, Peter G Kremsner, Michael Theisen
BACKGROUND: GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. METHODS: Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL...
August 31, 2016: Vaccine
T R Pavan, J Di Domenico, K S Kirsten, C O Nied, R Frandoloso, L C Kreutz
Adjuvants are essential to boost the immune response to inoculated antigen and play a central role in vaccine development. In this study, we investigated the efficacy of several adjuvants in the production of anti-bovine serum albumin (BSA) antibodies in silver catfish. Two hundred and seventy juvenile silver catfish (60-80 g) of both sexes were intraperitoneally vaccinated with BSA (200 µg/fish) alone or mixed to the following adjuvants: Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), aluminum hydroxide (AlOH), Montanide, four types of cytosine-phosphate-guanine (CpG) oligodeoxynucleotides (ODNs) and three concentrations of β-glucan, and the immune enhancing property was evaluated by measuring anti-BSA antibodies in blood samples at biweekly intervals...
July 25, 2016: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Miaoge Xue, Linqi Yu, Lianzhi Jia, Yijian Li, Yuanjun Zeng, Tingdong Li, Shengxiang Ge, Ningshao Xia
In attempts to develop recombinant subunit vaccines against rotavirus disease, it was previously shown that the N-terminal truncated VP8* protein, VP8-1 (aa26-231), is a good vaccine candidate when used for immunization in combination with Freund's adjuvant. However, this protein stimulated only weak immune response when aluminum hydroxide was used as an adjuvant. In this study, the nontoxic B subunit of cholera toxin (CTB) was employed as intra-molecular adjuvant to improve the immunogenicity of VP8-1. Both, the N-terminal and C-terminal fusion proteins, were purified to homogeneity, at which stage they formed pentamers, and showed significantly higher immunogenicity and protective efficacy than a VP8-1 /aluminum hydroxide mixture in a mouse model...
July 19, 2016: Human Vaccines & Immunotherapeutics
A Nazmi, R Hauck, A Davis, M Hildebrand, L B Corbeil, R A Gallardo
Diatoms are single cell eukaryotic microalgae; their surface possesses a porous nanostructured silica cell wall or frustule. Diatomaceous earth (DE) or diatomite is a natural siliceous sediment of diatoms. Since silica has been proved to have adjuvant capabilities, we propose that diatoms and DE may provide an inexpensive and abundant source of adjuvant readily available to use in livestock vaccines.In a first experiment, the safety of diatoms used as an adjuvant for in-ovo vaccination was investigated. In a second experiment, we assessed the humoral immune response after one in-ovo vaccination with inactivated Newcastle Disease Virus (NDV) and DE as adjuvant followed by 2 subcutaneous boosters on d 21 and 29 of age...
July 18, 2016: Poultry Science
Rotem Inbar, Ronen Weiss, Lucija Tomljenovic, Maria-Teresa Arango, Yael Deri, Christopher A Shaw, Joab Chapman, Miri Blank, Yehuda Shoenfeld
Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. We sought to evaluate the effects of Al adjuvant and the HPV vaccine Gardasil versus the true placebo on behavioral and inflammatory parameters in female mice. Six-week-old C57BL/6 female mice were injected with either, Gardasil, Gardasil + pertussis toxin (Pt), Al hydroxide, or, vehicle control in amounts equivalent to human exposure...
July 16, 2016: Immunologic Research
Germie P J M van den Dobbelsteen, Kellen C Faé, Jan Serroyen, Ingrid M van den Nieuwenhof, Martin Braun, Micha A Haeuptle, Dominique Sirena, Joerg Schneider, Cristina Alaimo, Gerd Lipowsky, Veronica Gambillara-Fonck, Michael Wacker, Jan T Poolman
BACKGROUND: Extra-intestinal pathogenic Escherichia coli (ExPEC) are major human pathogens; however, no protective vaccine is currently available. We assessed in animal models the immunogenicity and safety of a 4-valent E. coli conjugate vaccine (ExPEC-4V, serotypes O1, O2, O6 and O25 conjugated to Exotoxin A from Pseudomonas aeruginosa (EPA)) produced using a novel in vivo bioconjugation method. METHODS: Three doses of ExPEC-4V (with or without aluminum hydroxide) were administered to rabbits (2μg or 20μg per O-antigen, subcutaneously), mice (0...
July 29, 2016: Vaccine
Agnese Donadei, Cristiana Balocchi, Francesca Mancini, Daniela Proietti, Simona Gallorini, Derek T O'Hagan, Ugo D'Oro, Francesco Berti, Barbara C Baudner, Roberto Adamo
Conjugation of a small molecule immunopotentiator to antigens has been proposed to deliver the ligand to the receptor, localize its action and minimize systemic inflammation. However, the effect of conjugation of Toll like receptor 7 agonists (TLR7a) on the immunogenicity of carbohydrate-based vaccines is unknown. In this study we synthesized an anti-Neisseria meningitidis serogroup C (MenC) glycoconjugate vaccine composed of MenC oligosaccharide antigens covalently linked to the carrier protein CRM197, to which a TLR7a was in turn conjugated...
October 2016: European Journal of Pharmaceutics and Biopharmaceutics
Ting Fang, Jun Ren, Jinlong Zhang, Kexin Yin, Xiuxu Yang, Rui Yu, Xiaopeng Zhang, Changming Yu
Recombinant Fl-V (rFl-V) fusion protein is the main ingredient of the current candidate vaccine against Yersinia pestis infection, which has been under investigation in clinical trial in USA. We investigated the soluble expression conditions of rF1-V in Escherichia coli BL21 (DE3) that we constructed before. After scale-up and optimization of fermentation processes, we got the optimized fermentation process parameters: the culture was induced at the middle exponential phase with 50 µmol/L of IPTG at 25 °C for 5 h...
January 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Tsuguto Toda, Shin Yoshino
Nanomaterials present in cosmetics and food additives are used for industrial applications. However, their safety profile is unclear. Amorphous silica nanoparticles (nSPs) are a widely used nanomaterial and have been shown to induce inflammatory cytokines following intratracheal administration in mice. The current study investigated the adjuvant effect of nSP30 (nSP with a diameter of 33 nm) on T helper (Th)1, Th2, and Th17 immune responses as well as immunoglobulin (Ig) levels in mice. BALB/c mice were intraperitoneally administered ovalbumin (OVA) with or without varying doses and varying sizes of nSPs...
September 2016: International Journal of Immunopathology and Pharmacology
Feng-Juan Huang, Yi-Lei Ma, Ruo-Yu Tang, Wen-Ci Gong, Jun Li, Chun-Xia Chen, Lan Yin, Xiao-Ping Chen
Aluminium hydroxide (alum), the most widely used adjuvant in human and animal vaccines, has long been known to promote T helper type 2 (Th2) responses and Th2-associated humoral responses, but the mechanisms have remained poorly understood. In this study, we explored whether alum is able to directly modulate antigen-presenting cells to enhance their potency for Th2 polarization. We found that alum treatment of dendritic cells failed to show any Th2-promoting activities. In contrast, alum was able to enhance the capacity of basophils to induce Th2 cells...
October 2016: Immunology
Songhua Shan, Stan Fenwick, Trevor Ellis, Eddy Poinern, John Edwards, Xuan Le, Zhongtao Jiang
This study assessed the ability of three adjuvants (aluminum hydroxide, Essai (microparticle) and Phema (nanoparticle)) to enhance the immune response of chickens to an H6N2 avian influenza DNA vaccine. No hemagglutination inhibition (HI) antibody was detected following two intramuscular immunizations with the adjuvanted and non-adjuvanted pCAG-HAk vaccine, which has previously been shown to induce moderate H6 HA antibody response in SPF chickens. Following virus challenge, neither the vaccinated group without adjuvant nor the Essai adjuvanted group showed a statistically significant reduction in virus shedding in oropharyngeal and cloacal swabs compared with the naïve control group...
June 17, 2016: Avian Pathology: Journal of the W.V.P.A
Alex Cortez, Yongkai Li, Andrew T Miller, Xiaoyue Zhang, Kathy Yue, Jillian Maginnis, Janice Hampton, De Shon Hall, Michael Shapiro, Bishnu Nayak, Ugo D'Oro, Chun Li, David Skibinski, M Lamine Mbow, Manmohan Singh, Derek T O'Hagan, Michael P Cooke, Nicholas M Valiante, Tom Y-H Wu
Small molecule Toll-like receptor 7 (TLR7) agonists have been used as vaccine adjuvants by enhancing innate immune activation to afford better adaptive response. Localized TLR7 agonists without systemic exposure can afford good adjuvanticity, suggesting peripheral innate activation (non-antigen-specific) is not required for immune priming. To enhance colocalization of antigen and adjuvant, benzonaphthyridine (BZN) TLR7 agonists are chemically modified with phosphonates to allow adsorption onto aluminum hydroxide (alum), a formulation commonly used in vaccines for antigen stabilization and injection site deposition...
June 23, 2016: Journal of Medicinal Chemistry
Harm HogenEsch, Anisa Dunham, Elodie Burlet, Fangjia Lu, Yung-Yi C Mosley, Garry Morefield
A recombinant vaccine composed of a fusion protein formulated with aluminum hydroxide adjuvant is under development for protection against diseases caused by Streptococcus pyogenes. The safety and local reactogenicity of the vaccine was assessed by a comprehensive series of clinical, pathologic and immunologic tests in preclinical experiments. Outbred mice received three intramuscular injections of 1/5th of the human dose (0.1 ml) and rabbits received two injections of the full human dose. Control groups received adjuvant or protein antigen...
May 30, 2016: Journal of Applied Toxicology: JAT
Hsiaoling Wang, Nagarani Pampati, William M McCormick, Lokesh Bhattacharyya
We report development and validation of a simple, rapid, and accurate method for the quantitation of protein nitrogen, which combines Kjeldahl digestion and ion chromatography with suppressed conductivity detection and requires nanomolar amount of nitrogen in samples (≥10 μg protein). The mechanism of suppressed conductivity detection does not permit analysis of samples containing copper (present in Kjeldahl digestion solution) and aluminum (present in many vaccines as adjuvants) due to precipitation of their hydroxides within the suppressor...
June 2016: Journal of Pharmaceutical Sciences
Xiaoyan Li, Liru Guo, Mei Kong, Xu Su, Dongjing Yang, Ming Zou, Yinghua Liu, Likun Lu
OBJECTIVES: No licensed vaccines or therapeutic agents for human metapneumovirus (hMPV) infection exist to date. We aimed to construct a multi-epitope peptide (MEP) of hMPV to show promising results for epitope-based vaccine development. METHODS: Six independent algorithms were screened to predict B-cell epitopes of hMPV, and three algorithms were used to predict cytotoxic T lymphocyte and T helper (Th) lymphocyte epitopes. Predicted epitopes were assembled in series with the spacers GPGPG and KK introduced, termed MEP...
2015: Intervirology
Darren S Heeke, Rui Lin, Eileen Rao, Jennifer C Woo, Michael P McCarthy, Jason D Marshall
Childhood infection with Epstein-Barr virus (EBV) is often asymptomatic and may result in mild flu-like symptoms, but exposure during adolescence and young adulthood can lead to acute infectious mononucleosis (AIM) with a pathology characterized by swollen lymph nodes, sore throat, and severe fatigue lasting weeks or months. A vaccine targeting the envelope glycoprotein gp350 adjuvanted with aluminum hydroxide complexed with the TLR4 agonist monophosphoryl lipid A (MPLA) achieved a 78% reduction in AIM incidence in a small phase II trial of college-age individuals, but development of this vaccine was halted by the manufacturer...
May 17, 2016: Vaccine
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