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Alum adjuvant

Tetsuo Nakayama
The humoral and cellular immune responses of adaptive immunity are induced following immunization with effective vaccines. They induce functional cytokines and chemokines through the binding of vaccine components or adjuvants to innate immune receptors. Alum-adjuvanted vaccines induce local inflammatory nodules at injection sites, and the systemic and local production of the inflammatory cytokines, IL-1β, IL-6, and TNF-α, has been reported to occur three hours after vaccinations. Furthermore, G-CSF levels increase at injection sites...
October 13, 2016: Vaccine
Kelly M Rausch, Daming Zhu
The quantification of antigens adsorbed to aluminum-based adjuvants (alum) typically involves a method that first extracts antigen from the alum followed by the quantification of the antigen available in the extract. Extraction procedures often result in less than 100 % desorption of the antigen from the alum adjuvant and may alter the conformation of the antigen, reducing the accuracy of the subsequent method used for quantification. There is no generic method available for directly assessing the protein content when formulated on alum...
2017: Methods in Molecular Biology
John D Campbell
The development of aluminum salts (alum) as vaccine adjuvants was an empirical process with little understanding of the mechanism of action and, with decades of use, it has become clear that there is a need for alternatives where alum-based adjuvants are suboptimal. Oligonucleotides containing unmethylated CpG sequences represent one alternative as they are potent stimulators of the vertebrate innate immune system through activation of Toll-like receptor-9. This chapter outlines the methods used by Dynavax Technologies to progress a CpG-containing oligonucleotide sequence termed 1018 through preclinical and clinical testing as an adjuvant for immunization against hepatitis B virus (HBV)...
2017: Methods in Molecular Biology
Ruchi R Shah, Kimberly J Hassett, Luis A Brito
Adjuvants are included in sub-unit or recombinant vaccines to enhance the potency of poorly immunogenic antigens. Adjuvant discovery is as complex as it is a multidiscplinary intersection of formulation science, immunology, toxicology, and biology. Adjuvants such as alum, which have been in use for the past 90 years, have illustrated that adjuvant research is a methodical process. As science advances, new analytical tools are developed which allows us to delve deeper into the various mechanisms that generates a potent immune response...
2017: Methods in Molecular Biology
Atsushi Kimishima, Cody J Wenthur, Lisa M Eubanks, Shun Sato, Kim D Janda
Although cocaine abuse and addiction continue to cause serious health and societal problems, an FDA-approved medication to treat cocaine addiction has yet to be developed. Employing a pharmacokinetic strategy, an anti-cocaine vaccine, provides an attractive avenue to address these issues, however, current vaccines have shown varying degrees of efficacy, indicating that further formulation is necessary. As a means to improve vaccine efficacy, we examined the effects of varying anti-cocaine vaccine formulations by combining a Toll-like receptor 9 (TLR9) agonist with a TLR5 agonist in the presence of alum...
October 7, 2016: Molecular Pharmaceutics
Joanne M Langley, Naresh Aggarwal, Azhar Toma, Scott A Halperin, Shelly A McNeil, Laurence Fissette, Walthere Dewé, Maarten Leyssen, Jean-François Toussaint, Ilse Dieussaert
BACKGROUND:  RSV is a leading cause of childhood bronchiolitis and pneumonia, particularly in early infancy. Immunization of pregnant women could boost pre-existing immune responses, providing passive protection to the newborn through placental transfer of anti-RSV antibody. METHODS:  In this first-in-humans clinical trial of a purified recombinant RSV protein F vaccine engineered to preferentially maintain pre-fusion conformation (RSV-PreF), 128 healthy men 18-44 years old were randomized to one dose of a RSV-PreF vaccine containing 10, 30 or 60 µg of RSV-PreF antigen with or without alum adjuvant, or control, and followed for one year for safety and immunogenicity outcomes...
September 29, 2016: Journal of Infectious Diseases
Jean-Daniel Masson, Michel Thibaudon, Laurent Bélec, Guillemette Crépeaux
Calcium phosphate was used as an adjuvant in France in diphtheria, tetanus, pertussis and poliomyelitis vaccines. It was later completely substituted by alum salts in the late 80's, but it still remains as an approved adjuvant for the World Health Organization for human vaccination. Area covered: Thus, calcium phosphate is now considered as one of the substances that could replace alum salts in vaccines. The aim of this paper is to draw a review of existing data on calcium phosphate as an adjuvant in order to bring out the strengths and weaknesses for its use on a large scale...
October 3, 2016: Expert Review of Vaccines
Vidisha Minhas, Abhinav Shrestha, Neerja Wadhwa, Rita Singh, Satish Kumar Gupta
Improvements in long-term female contraception can be achieved by vaccinating with sperm-derived proteins. Here, recombinant proteins comprising either (i) N- (amino acid residues 1-80) or C- (amino acid residues 76-126) terminal fragments of mouse sperm protein 17 (Sp17) fused to the promiscuous T non-B cell epitope of tetanus toxoid (TT), amino acid residues 830-844 followed by di-lysine linker (KK) (TT-KK-Sp17N or TT-KK-Sp17C , respectively) or (ii) mouse equatorin (amino acid residues 21-185) fused to the T non-B cell epitope of bovine RNase (amino acid residues 94-104) were expressed in Escherichia coli...
September 27, 2016: Molecular Reproduction and Development
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
Brian M Friedrich, David W C Beasley, Jai S Rudra
A crucial issue in vaccine development is to balance safety with immunogenicity. The low immunogenicity of most subunit antigens warrants a search for adjuvants able to stimulate both cell-mediated and humoral immunity. In recent years, successful applications of nanotechnology and bioengineering in the field of vaccine development have enabled the production of novel adjuvant technologies. In this work, we investigated totally synthetic and supramolecular peptide hydrogels as novel vaccine adjuvants in conjunction with the immunoprotective envelope protein domain III (EIII) of West Nile virus as an immunogen in a mouse model...
September 23, 2016: Vaccine
Miriam A Balderas, Chinh Nguyen, Austen Terwilliger, Wendy A Keitel, Angelina Iniguez, Rodrigo Torres, Frederico Palacios, Celia W Goulding, Anthony W Maresso
Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S. licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed - AVA) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multi-shot regimen, recommended boosters, and potential for adverse reactions...
September 19, 2016: Infection and Immunity
Krishnamurthy Konduru, Amy C Shurtleff, Steven B Bradfute, Siham Nakamura, Sina Bavari, Gerardo Kaplan
Ebola virus (EBOV), a member of the Filoviridae that can cause severe hemorrhagic fever in humans and nonhuman primates, poses a significant threat to the public health. Currently, there are no licensed vaccines or therapeutics to prevent and treat EBOV infection. Several vaccines based on the EBOV glycoprotein (GP) are under development, including vectored, virus-like particles, and protein-based subunit vaccines. We previously demonstrated that a subunit vaccine containing the extracellular domain of the Ebola ebolavirus (EBOV) GP fused to the Fc fragment of human IgG1 (EBOVgp-Fc) protected mice against EBOV lethal challenge...
2016: PloS One
Duncheng Wang, Debjani Ghosh, S M Touhidul Islam, Cody D Moorman, Ashton E Thomason, Daniel S Wilkinson, Mark D Mannie
This study introduces a flexible format for tolerogenic vaccination that incorporates IFN-β and neuroantigen (NAg) in the Alum adjuvant. Tolerogenic vaccination required all three components, IFN-β, NAg, and Alum, for inhibition of experimental autoimmune encephalomyelitis (EAE) and induction of tolerance. Vaccination with IFN-β + NAg in Alum ameliorated NAg-specific sensitization and inhibited EAE in C57BL/6 mice in pretreatment and therapeutic regimens. Tolerance induction was specific for the tolerogenic vaccine Ag PLP178-191 or myelin oligodendrocyte glycoprotein (MOG)35-55 in proteolipid protein- and MOG-induced models of EAE, respectively, and was abrogated by pretreatment with a depleting anti-CD25 mAb...
September 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Narges Khabazzadeh Tehrani, Mehdi Mahdavi, Fatemeh Maleki, Somayeh Zarrati, Fatemeh Tabatabaie
Leishmaniasis is a parasitic disease caused by several species of the genus Leishmania. Montanide ISA 70 is an adjuvant composed of a natural metabolizable oil and a very refined emulsifier from the manide monooleate family. The TSA (thiol-specific antioxidant) is a important antigen of Leishmania major. The purpose of this work was protein-vaccine efficacy as an protection and excellent candidate in the presence Montanide. The expression of recombinant protein was confirmed with SDS (sodium dodecyl sulfate) page and Western bloting...
September 2016: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Matthew D Gallovic, Kevin L Schully, Matthew G Bell, Margaret A Elberson, John R Palmer, Christian A Darko, Eric M Bachelder, Barbara E Wyslouzil, Andrea M Keane-Myers, Kristy M Ainslie
Subunit formulations are regarded as the safest type of vaccine, but they often contain a protein-based antigen that can result in significant challenges, such as preserving antigenicity during formulation and administration. Many studies have demonstrated that encapsulation of protein antigens in polymeric microparticles (MPs) via emulsion techniques results in total IgG antibody titers comparable to alum formulations, however, the antibodies themselves are non-neutralizing. To address this issue, a coaxial electrohydrodynamic spraying (electrospray) technique is used to formulate a microparticulate-based subunit anthrax vaccine under conditions that minimize recombinant protective antigen (rPA) exposure to harsh solvents and high shear stress...
September 5, 2016: Advanced Healthcare Materials
Su-Jin Park, Young-Jae Si, Jihye Kim, Min-Suk Song, Se-Mi Kim, Eun-Ha Kim, Hyeok-Il Kwon, Young-Il Kim, Ok-Jun Lee, Ok Sarah Shin, Chul-Joong Kim, Eui-Cheol Shin, Young Ki Choi
To investigate cross-protective vaccine efficacy of highly-pathogenic avian influenza H5N1 viruses against a recent HPAI H5N8 virus, we immunized C57BL/6 mice and ferrets with three alum-adjuvanted inactivated whole H5N1 vaccines developed through reverse-genetics (Rg): [Vietnam/1194/04xPR8 (clade 1), Korea/W149/06xPR8 (clade 2.2), and Korea/ES223N/03xPR8 (clade 2.5)]. Although relatively low cross-reactivities (10-40 HI titer) were observed against heterologous H5N8 virus, immunized animals were 100% protected from challenge with the 20 mLD50 of H5N8 virus, with the exception of mice vaccinated with 3...
November 2016: Virology
Vahid Asgary, Alireza Shoari, Fahimeh Baghbani-Arani, Seyed Ataollah Sadat Shandiz, Mohammad Sadeq Khosravy, Alireza Janani, Razieh Bigdeli, Rouzbeh Bashar, Reza Ahangari Cohan
BACKGROUND: Green synthesis of nanoparticles by plant extracts plays a significant role in different applications. Recently, several studies were conducted on the use of nanoparticles as adjuvant. The main aim of this study was to evaluate green synthesized silver nanoparticles (AgNPs) as adjuvant in rabies veterinary vaccine and compare the results with the existing commercially available alum adjuvant. MATERIALS AND METHODS: In the current study, AgNPs were prepared by the reduction of aqueous silver nitrate by leaf extract of Eucalyptus procera...
2016: International Journal of Nanomedicine
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
Kristel L Emmer, Lindsay Wieczorek, Steven Tuyishime, Sebastian Molnar, Victoria R Polonis, Hildegund C J Ertl
OBJECTIVES: Over 2 million individuals are infected with HIV type 1 (HIV-1) each year, yet an effective vaccine remains elusive. The most successful HIV-1 vaccine to date demonstrated 31% efficacy. Immune correlate analyses associated HIV-1 envelope (Env)-specific antibodies with protection, thus providing a path toward a more effective vaccine. We sought to test the antibody response from novel prime-boost vaccination with a chimpanzee-derived adenovirus (AdC) vector expressing a subtype C Env glycoprotein (gp)140 combined with either a serologically distinct AdC vector expressing gp140 of a different subtype C isolate or an alum-adjuvanted, partially trimeric gp145 from yet another subtype C isolate...
October 23, 2016: AIDS
Gaurav Gupta, Viviana Giannino, Narayan Rishi, Reinhard Glueck
Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver...
September 7, 2016: Vaccine
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