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Alum adjuvant

Seo-Yeon Jung, Kyung Won Kang, Eun-Young Lee, Dong-Won Seo, Hong-Lim Kim, Hak Kim, TaeWoo Kwon, Hye-Lim Park, Hun Kim, Sang-Myeong Lee, Jae-Hwan Nam
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic and zoonotic virus with a fatality rate in humans of over 35%. Although several vaccine candidates have been developed, there is still no clinically available vaccine for MERS-CoV. In this study, we developed two types of MERS-CoV vaccines: a recombinant adenovirus serotype 5 encoding the MERS-CoV spike gene (Ad5/MERS) and spike protein nanoparticles formulated with aluminum (alum) adjuvant. Next, we tested a heterologous prime-boost vaccine strategy, which compared priming with Ad5/MERS and boosting with spike protein nanoparticles and vice versa, with homologous prime-boost vaccination comprising priming and boosting with either spike protein nanoparticles or Ad5/MERS...
May 5, 2018: Vaccine
Scott A Budda, Lauren A Zenewicz
Mucosal vaccines are a promising platform for combatting infectious diseases for which we still lack effective preventative measures. Optimizing these vaccines to generate the best protective immune responses with the least complicated immunization regimen is imperative. Mucosal barriers are the first line of defense against many pathogens and, as such, we looked to their biology for strategies to improve vaccine delivery. Interleukin-22 (IL-22) is a key cytokine in both healthy and inflamed mucosal tissues...
May 5, 2018: Vaccine
Shokouhi Hadiseh, Farahmand Behrokh, Ghaemi Amir, Mazaheri Vahideh, Fotouhi Fatemeh
Influenza viruses are globally important respiratory pathogens with high degree of morbidity and mortality during annual epidemics. Influenza A vaccination has been challenged due to genetic evolution. M2 protein is the surface antigen of the virus and facilitates virus entry into the host cells. N-terminal 24 amino acid residues that constitute the extracellular domain of M2 protein (M2e) show remarkable conservation among all subtypes of influenza A viruses. The aim of the present study was to investigate the effects of using HSP70 as an adjuvant fused to three tandem repeats of M2e (3M2e) to enhance the immune responses against influenza A challenge...
May 3, 2018: Virus Research
Hakim Azizi, Hadi Mirzaeei, Ali Akbar Nasiri, Ali Bazi, Aliyar Mirzapour, Mehrdad Khatami, Kareem Hatam Nahavandi, Ako Azimi, Hajar Yaghoobi
Toxic effects of available therapeutics are major drawbacks for conventional management approaches in parasitic infections. Vaccines have provided a promising opportunity to obviate such unwanted complications. In present study, we examined immune augmenting capacities of an emerging adjuvant, Naltrexone, against Fasciola hepatica infection in BALB/c mice. Seventy BALB/c mice were divided into five experimental groups (14 mice per group) including 1- control (received PBS), 2- vaccine (immunized with F. hepatica E/S antigens), 3- Alum-vaccine (immunized with Alum adjuvant and E/S antigens), 4- NLT-vaccine (immunized with NLT adjuvant and E/S antigens), and 5- Alum-NLT-vaccine (immunized with mixed Alum-NLT adjuvant and E/S antigens)...
April 27, 2018: Experimental Parasitology
Naoko Matsubara, Akihiro Imamura, Tatsuya Yonemizu, Chizuru Akatsu, Hongrui Yang, Akiharu Ueki, Natsuki Watanabe, Hajjaj Abdu-Allah, Nobutaka Numoto, Hiromu Takematsu, Shinobu Kitazume, Thomas F Tedder, Jamey D Marth, Nobutoshi Ito, Hiromune Ando, Hideharu Ishida, Makoto Kiso, Takeshi Tsubata
Sialic acid-binding immunoglobulin-like lectins (Siglecs) are expressed in various immune cells and most of them carry signaling functions. High-affinity synthetic sialoside ligands have been developed for various Siglecs. Therapeutic potentials of the nanoparticles and compounds that contain multiple numbers of these sialosides and other reagents such as toxins and antigens have been demonstrated. However, whether immune responses can be regulated by monomeric sialoside ligands has not yet been known. CD22 (also known as Siglec-2) is an inhibitory molecule preferentially expressed in B lymphocytes (B cells) and is constitutively bound and functionally regulated by α2,6 sialic acids expressed on the same cell (cis-ligands)...
2018: Frontiers in Immunology
Hoa Thi My Vo, Barbara Christiane Baudner, Stefano Sammicheli, Matteo Iannacone, Ugo D'Oro, Diego Piccioli
Vaccination is one of the most cost-effective health interventions and, with the exception of water sanitization, no other action has had such a major effect in mortality reduction. Combined with other approaches, such as clean water, better hygiene, and health education, vaccination contributed to prevent millions of cases of deaths among children under 5 years of age. New or improved vaccines are needed to fight some vaccine-preventable diseases that are still a threat for the public health globally, as reported also in the Global Vaccine Action Plan (GVAP) endorsed by the World Health Assembly in 2012...
2018: Frontiers in Immunology
Xue Chen, Ting Zhang, Hongyang Liu, Yaru Hao, Guoyang Liao, Xuemei Xu
Current available human papillomavirus (HPV) vaccines are based on the major capsid protein L1 virus-like particles (VLPs), which mainly induce type-specific neutralizing antibodies against vaccine types. Continuing to add more types of VLPs in a vaccine raises the complexity and cost of production which remains the principal impediment to achieve broad implementation of HPV vaccines, particularly in developing regions. In this study, we constructed 16L1-31L2 chimeric VLP (cVLP) by displaying HPV31 L2 aa.17-38 on the h4 coil surface region of HPV16 L1, and assessed its immunogenicity in mouse model...
April 23, 2018: Human Vaccines & Immunotherapeutics
Erika Garner-Spitzer, Claudia Seidl-Friedrich, Ines Zwazl, Michael Hofer, Tamar Kinaciyan, Reinhart Jarisch, Karin Stiasny, Gerhard J Zlabinger, Michael Kundi, Ursula Wiedermann
BACKGROUND: Allergic diseases are caused by Th2-driven immune responses and their treatment with specific immunotherapy (SIT) leads to immunomodulation via IL10, TGF-ß and Th1/Tr1 shift. This phase IV, open-label clinical trial investigated whether allergies and SIT treatment influenced immune responses to routine vaccination. METHODS: We studied three groups: 49 allergic patients (allergic group), 21 allergic patients receiving maintenance doses of SIT (SIT group), and 49 non-allergic controls...
May 11, 2018: Vaccine
Gabriel Ozorowski, Albert Cupo, Michael Golabek, Michelle LoPiccolo, Thomas A Ketas, Matt Cavallary, Christopher A Cottrell, P J Klasse, Andrew B Ward, John P Moore
Native-like, soluble, recombinant SOSIP trimers of various designs and based on several env genes of human immunodeficiency virus type 1 (HIV-1) are being tested as immunogens in different animal models. These experiments almost always involve co-formulating the trimers with an adjuvant to boost the magnitude of the immune responses. One factor relevant to the choice of an adjuvant is that it should not physically damage the immunogen or impede its ability to present relevant epitopes. As examples, an adjuvant formulation that includes harsh detergents could disrupt the structural integrity of a trimer, and any charged compounds in the formulation could bind to counter-charged regions of the trimer and physically occlude nearby epitopes...
April 18, 2018: Journal of Virology
Justyna Gatkowska, Marek Wieczorek, Bożena Dziadek, Katarzyna Dzitko, Jarosław Dziadek, Henryka Długońska
The aim of this study was to evaluate the immunogenic and immunoprotective activities and to determine the neuroprotective capacity of the tetravalent vaccine containing selected recombinant T. gondii antigens (ROP2 + ROP4 + SAG1 + MAG1) administered with safe adjuvants (MPL and alum) using male and female inbred mice. The tested antigenic combination provided partial protection against brain cyst formation, especially in males (reduction in cyst burden by 72%). The decrease in cyst burden was observed for the whole brain as well as for specified brain regions associated with natural defensive behaviors, emotion processing and integration of motor and sensory stimuli...
April 30, 2018: Veterinary Parasitology
Randall Hyer, Darren K McGuire, Biao Xing, Sam Jackson, Robert Janssen
BACKGROUND: Hepatitis B virus infection remains an important global public health problem. Approved alum-adjuvanted vaccines are well tolerated but require three doses and have reduced immunogenicity in adults. A two-dose vaccine containing hepatitis B surface antigen combined with a novel, Toll-like receptor 9 agonist adjuvant (HBsAg-1018 [HEPLISAV-B®]) has demonstrated significantly higher seroprotection rates than a three dose vaccine. METHODS: A post hoc analysis compared the safety of HBsAg-1018 with HBsAg-Eng (Engerix-B®), in three randomized, observer-blinded, active-controlled, multi-center phase 3 trials in adults...
April 5, 2018: Vaccine
Yao Deng, Jiaming Lan, Linlin Bao, Baoying Huang, Fei Ye, Yingzhu Chen, Yanfeng Yao, Wenling Wang, Chuan Qin, Wenjie Tan
The persistent public health threat of infection with Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective and safe MERS-CoV vaccine. In this study, we prepared and vaccinated mice with either a Spike (S) protein or inactivated whole MERS-CoV (IV) with a combined adjuvant (alum+CpG) as a vaccine formulation. Similar levels of the anti-S protein IgG response and neutralizing activity were induced by both the S protein and IV vaccines. In addition, immune responses against three other structural proteins, the envelope (E), membrane (M), and nucleocapsid (N) proteins, were also detected in sera of mice that received IV...
April 4, 2018: Emerging Microbes & Infections
William L Willis, Linan Wang, Takuma Tsuzuki Wada, Mark Gardner, Omar Abdouni, Jeffrey Hampton, Giancarlo Valiente, Nicholas Young, Stacy Ardoin, Sudha Agarwal, Michael A Freitas, Lai-Chu Wu, Wael N Jarjour
High-mobility group box 1 (HMGB1) is a chromatin-associated protein that in response to stress or injury, translocates from the nucleus to the extracellular milieu where it functions as an alarmin. HMGB1's function is in part determined by the complexes (HMGB1c) it forms with other molecules. However, structural modifications in the HMGB1 polypeptide that may regulate HMGB1c formation have not been previously described. In this report, we observed high-molecular weight, denaturing-resistant HMGB1c in the plasma and peripheral blood mononuclear cells of individuals with systemic lupus erythematosus (SLE) and to a much lesser extent in healthy subjects...
April 4, 2018: Journal of Biological Chemistry
Joanne M Langley, Lisa D MacDonald, Genevieve M Weir, Donna MacKinnon-Cameron, Lingyun Ye, Shelly McNeil, Bert Schepens, Xavier Saelens, Marianne M Stanford, Scott A Halperin
Background: Respiratory Syncytial Virus infection can cause lower respiratory tract infection in older adults comparable to influenza, but no vaccines are available. Methods: This was a randomized, observer blinded first-in-humans study of a novel synthetic RSV antigen SHe, formulated with either the lipid and oil-based vaccine platform, DepoVaxTM, termed DPX-RSV(A), or with alum, termed (RSV(A) SHe, in healthy 50-64-year-old adults. Two dose levels (10 or 25 µg) of the SHe antigen with each formulation were compared to placebo...
March 30, 2018: Journal of Infectious Diseases
Ana Paula M M Almeida, Leopoldo F M Machado, Daniel Doro, Frederico C Nascimento, Leonardo Damasceno, Ricardo Tostes Gazzinelli, Ana Paula Fernandes, Caroline Junqueira
Visceral leishmaniasis (VL) is a major public health issue reported as the second illness in mortality among all tropical diseases. Clinical trials have shown that protection against VL is associated with robust T cell responses, especially those producing IFN-γ. The Leishmania amastigote 2 (A2) protein has been repeatedly described as immunogenic and protective against VL in different animal models; it is recognized by human T cells, and it is also commercially available in a vaccine formulation containing saponin against canine VL...
2018: Frontiers in Immunology
Danielle A Wagner-Muñiz, Shannon L Haughney, Sean M Kelly, Michael J Wannemuehler, Balaji Narasimhan
Streptococcus pneumoniae is a major causative agent of pneumonia, a debilitating disease particularly in young and elderly populations, and is the leading worldwide cause of death in children under the age of five. While there are existing vaccines against S. pneumoniae , none are protective across all serotypes. Pneumococcal surface protein A (PspA), a key virulence factor of S. pneumoniae , is an antigen that may be incorporated into future vaccines to address the immunological challenges presented by the diversity of capsular antigens...
2018: Frontiers in Immunology
Deborah S Leuthard, Agathe Duda, Sandra N Freiberger, Sina Weiss, Isabella Dommann, Gabriele Fenini, Emmanuel Contassot, Matthias F Kramer, Murray A Skinner, Thomas M Kündig, Matthew D Heath, Pål Johansen
Allergen immunotherapy (AIT) is the only modality that can modify immune responses to allergen exposure, but therapeutic coverage is low. One strategy to improve AIT safety and efficacy is the use of new or improved adjuvants. This study investigates immune responses produced by microcrystalline tyrosine (MCT)-based vaccines as compared with conventional aluminum hydroxide (alum). Wild-type, immune-signaling-deficient, and TCR-transgenic mice were treated with different Ags (e.g., OVA and cat dander Fel d 1), plus MCT or alum as depot adjuvants...
March 28, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Diego Angosto, Azucena López-Muñoz, Alicia García-Alcazar, José Meseguer, María P Sepulcre, Victoriano Mulero
Although Aluminum salts (Alum) have been extensively used in human vaccination for decades, its mechanism of action is controversial. In fish, the use of Alum as a vaccine adjuvant is scarce and there are no studies aimed at identifying its mechanism of action. In the present study we report that Alum is a powerful adjuvant in the gilthead seabream (Sparus aurata L., Sparidae) and the European seabass (Dicentrarchus labrax L. Moronidae). Thus, Alum increased the specific antibody titers to the model antigen keyhole limpet hemocyanin as the commonly used Freund's adjuvant did in both species...
March 22, 2018: Developmental and Comparative Immunology
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
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