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Maopeng Tian, Zijie Zhou, Songwei Tan, Xionglin Fan, Longmeng Li, Nadeem Ullah
Despite the vaccine Mycobacterium bovis Bacillus Calmette-Guérin is used worldwide, tuberculosis (TB) remains the first killer among infectious diseases. An effective vaccine is urgently required. DNA vaccine has shown prophylactic as well as therapeutic effects against TB, while its weak immunogenicity hinders the application. As a strong inducer of Th1-biased immune response, DMT, consisting of dimethyldioctadecylammonium (DDA) and two pattern recognition receptor agonists monophosphoryl lipid A and trehalose 6,6'-dibehenate (TDB), was a newly developed liposomal adjuvant...
2018: Frontiers in Immunology
Kantrol Kumar Sahu, Ravi Shankar Pandey
The present study was undertaken with an aim to investigate potential of targeting colonic mucosa following oral vaccine delivery to generate prophylactic humoral and mucosal immune response. In present study, response surface methodology (RSM) using the central composite design (CCD) was applied for optimization of process and composition to get uniform, stable reproducible eudragit nanoparticles suitable for targeting to colon. The optimized formulation had the composition of 173 μg HBsAg, 250 mg polymers concentration (4:1 combination of Eudragit S-100 and L-100) and 2% w/v Polyvinyl alcohol (PVA) along with adjuvant Monophosphoryl lipid A (MPLA)...
February 22, 2018: Pharmaceutical Development and Technology
Sunita Minz, Ravi Shankar Pandey
Pulmonary vaccination is one of the most promising routes for immunization owing to its non-invasive nature and induction of strong mucosal immunity and systemic response. In the present study, recombinant hepatitis B surface antigen loaded solid fat nanoemulsions (SFNs) as carrier system and monophosphoryl lipid A (MPLA) as an adjuvant-carrier system was prepared and evaluated as multi adjuvanted vaccine system for deep pulmonary vaccination. Deposition and clearance from the deep lung of rats were determined by gamma scintigraphy...
February 15, 2018: Journal of Pharmaceutical Sciences
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
Maili Lehto, Henrik Wolff, Reko Leino, Harri Alenius, Johannes Savolainen
BACKGROUND: Allergen specific immunotherapy (SIT) effectively alleviates type I allergic diseases characterized by T helper (Th) 2-type immunity. Our recent studies have shown that a synthetic trivalent glycocluster, triacedimannose (TADM), suppresses the Th2-type allergic inflammation. The aim of this study was to compare TADM with two well-known adjuvants, unmethylated cytocine-phosphate-guanine oligodeoxynucleotide (CpG) and monophosphoryl lipid A (MPLA) in a grass allergen induced chronic allergic inflammation model in mice...
January 26, 2018: Allergy
Motao Zhu, Xilai Ding, Ruifang Zhao, Xuewu Liu, Haifa Shen, Chunmei Cai, Mauro Ferrari, Helen Y Wang, Rong-Fu Wang
Despite the importance and promise of cancer vaccines for broader prevention and treatment of cancer, limited clinical responses are observed, suggesting that key rational designs are required for inducing potent immune responses against cancer. Here we report a mesoporous silicon vector (MSV) as a multi-functional microparticle for formulating an efficient cancer vaccine composed of B16 melanoma derived-tyrosinase related protein 2 (TRP2) peptide and dual toll-like receptor (TLR) agonists. We demonstrated that MSV microparticles protected the peptide from rapid degradation for prolonged antigen presentation to immune cells...
January 8, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Ismat Khatri, Christian Alexander, Klaus Brandenburg, Zhiqi Chen, Adrian Heini, Didier Heumann, Jean-Pierre Mach, Vienna Mazzoli, Ernst Rietschel, Alexey Tersikh, Artur Ulmer, Kai Yu, Ulrich Zähringer, Reginald Gorczynski
Injections of a crude fetal sheep liver extract (FSLE) containing fetal hemoglobin, MPLA, and glutathione (GSSH) reversed cytokine changes in aged mice. To investigate the role of fetal hemoglobin we derived mice with homzygous deletions for either of the two major βchains, HgbβmaKO or HgbβmiKO. Hgbβmi is the most prominent fetal Hgbβ chain, with Hgbβma more prominent in adult mice. Mice lacking another fetal Hgb chain, HgbεKO, died in utero. CHO cells transfected with cloned Hgb chains were used to produce proteins for preparation of rabbit heteroantibodes...
January 4, 2018: Pharmacogenomics Journal
Wei Dong, Yoshita Bhide, Sonny Marsman, Marijke Holtrop, Tjarko Meijerhof, Jacqueline de Vries-Idema, Aalzen de Haan, Anke Huckriede
BACKGROUND: Induction of CD8+ cytotoxic T cells (CTLs) to conserved internal influenza antigens, such as nucleoprotein (NP), is a promising strategy for the development of cross-protective influenza vaccines. However, influenza NP protein alone cannot induce CTL immunity due to its low capacity to activate antigen-presenting cells (APCs) and get access to the MHC class I antigen processing pathway. METHODS: To facilitate the generation of NP-specific CTL immunity we developed a novel influenza vaccine consisting of virosomes with the Toll-like receptor 4 (TLR4) ligand monophosphoryl lipid A (MPLA) and the metal-ion-chelating lipid DOGS-NTA-Ni incorporated in the membrane...
December 26, 2017: Biotechnology Journal
Sunita Minz, Ravi Shankar Pandey
Traditional parenteral recombinant hepatitis B virus (HBV) vaccines have effectively reduced the disease burden despite being able to induce seroprotective antibody titers in 5-10% vaccinated individuals (non-responders). Moreover, an estimated 340 million chronic HBV cases are in need of treatment. Development of safe, stable, and more effective hepatitis B vaccine formulation would address these challenges. Recombinant hepatitis B surface antigen (rHBsAg) entrapped solid fat nanoemulsions (SFNs) containing monophosphoryl lipid A (MPLA) that was prepared and optimized by quality by design (QbD) using response surface methodology (RSM), i...
December 14, 2017: AAPS PharmSciTech
Masaki Ito, Kazumi Hayashi, Tamiko Minamisawa, Sadamu Homma, Shigeo Koido, Kiyotaka Shiba
Adjuvants are indispensable for achieving a sufficient immune response from vaccinations. From a functional viewpoint, adjuvants are classified into two categories: "physical adjuvants" increase the efficacy of antigen presentation by antigen-presenting cells (APC) and "signal adjuvants" induce the maturation of APC. Our previous study has demonstrated that a physical adjuvant can be encrypted into proteinous antigens by creating artificial proteins from combinatorial assemblages of epitope peptides and those peptide sequences having propensities to form certain protein structures (motif programming)...
2017: PloS One
Zongmin Zhao, Brian Harris, Yun Hu, Theresa Harmon, Paul R Pentel, Marion Ehrich, Chenming Zhang
Current clinically-tested nicotine vaccines have yet shown enhanced smoking cessation efficacy due to their low immunogenicity. Achieving a sufficiently high immunogenicity is a necessity for establishing a clinically-viable nicotine vaccine. This study aims to facilitate the immunogenicity of a hybrid nanoparticle-based nicotine vaccine by rationally incorporating toll-like receptor (TLR)-based adjuvants, including monophosphoryl lipid A (MPLA), Resiquimod (R848), CpG oligodeoxynucleotide 1826 (CpG ODN 1826), and their combinations...
February 2018: Biomaterials
Jiaming Guo, Yuanyuan Chen, Xiao Lei, Yang Xu, Zhe Liu, Jianming Cai, Fu Gao, Yanyong Yang
Ionizing radiation causes severe damage to human body, and normal tissue toxicity in cancer radiotherapy also limits its further application. It is urgently required to develop safe and effective radioprotector. Our previous study has shown that toll like receptor 4 (TLR4) was dispensable for basal radiation resistance. However, severe toxicity of its traditional agonist lipopolysaccharide limits the clinical application. In present study, we demonstrated that monophosphoryl lipid A (MPLA), a potent TLR4 agonist with low toxicity, effectively attenuated radiation injury on in vitro and in vivo ...
October 17, 2017: Oncotarget
Lizhen Wang, Shaojie Feng, Subo Wang, Hui Li, Zhongwu Guo, Guofeng Gu
A monophosphoryl lipid A (MPLA) derivative having the 6'-OH group substituted with an NH2 group was synthesized and coupled with the upstream terminal tetrasaccharide of mycobacterial lipoarabinomannan (LAM) via an amide bond to create a novel type of MPLA-based fully synthetic glycoconjugate vaccine. The same tetrasaccharide was also coupled with MPLA at the 1-O-position. Immunological activities of the two synthetic conjugates were evaluated in mice and compared. Both afforded robust overall and IgG antibody responses, but intraperitoneal injection elicited responses significantly stronger than those from subcutaneous injection...
December 1, 2017: Journal of Organic Chemistry
Paulina A García-González, Katina Schinnerling, Alejandro Sepúlveda-Gutiérrez, Jaxaira Maggi, Ahmed M Mehdi, Hendrik J Nel, Bárbara Pesce, Milton L Larrondo, Octavio Aravena, María C Molina, Diego Catalán, Ranjeny Thomas, Ricardo A Verdugo, Juan C Aguillón
There is growing interest in the use of tolerogenic dendritic cells (tolDCs) as a potential target for immunotherapy. However, the molecular bases that drive the differentiation of monocyte-derived DCs (moDCs) toward a tolerogenic state are still poorly understood. Here, we studied the transcriptional profile of moDCs from healthy subjects, modulated with dexamethasone (Dex) and activated with monophosphoryl lipid A (MPLA), referred to as Dex-modulated and MPLA-activated DCs (DM-DCs), as an approach to identify molecular regulators and pathways associated with the induction of tolerogenic properties in tolDCs...
2017: Frontiers in Immunology
Heqing Cao, Xiaohua Chang, Hailiang Mao, Jian Zhou, Zi Liang Wu, Guorong Shan, Yongzhong Bao, Pengju Pan
Physical hydrogels crosslinked by non-covalent interactions have attained increasing attention due to their good mechanical properties and processability. However, the use of feasible and controllable non-covalent interactions is highly essential for preparing such hydrogels. In this article, we report on stereocomplexed physical hydrogels prepared by simple casting and swelling of amphiphilic graft copolymers bearing a poly(acrylic acid) (PAA) backbone and poly(l-lactic acid) (PLLA) or poly(d-lactic acid) (PDLA) stereocomplexable side chains...
November 22, 2017: Soft Matter
A Landi, J Law, D Hockman, M Logan, K Crawford, C Chen, J Kundu, T Ebensen, C A Guzman, L Deschatelets, L Krishnan, D L J Tyrrell, M Houghton
Three decades after the discovery, hepatitis C virus (HCV) is still the leading cause of liver transplantation and poses a major threat to global health. In spite of recent advances in the development of direct acting antivirals, there is still a need for a prophylactic vaccine to limit the virus spread and protect at-risk populations, especially in developing countries, where the cost of the new treatments may severely limit access. The use of recombinant HCV glycoproteins E1E2 (rE1E2) in combination with the MF59, an oil-in-water emulsion-based adjuvant, has previously been shown to reduce the rate of chronicity in chimpanzees and to induce production of cross-neutralizing antibodies and cellular immune responses in human volunteers...
December 15, 2017: Vaccine
Mallika Sastry, Baoshan Zhang, Man Chen, M Gordon Joyce, Wing-Pui Kong, Gwo-Yu Chuang, Kiyoon Ko, Azad Kumar, Chiara Silacci, Michelle Thom, Andres M Salazar, Davide Corti, Antonio Lanzavecchia, Geraldine Taylor, John R Mascola, Barney S Graham, Peter D Kwong
Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV)-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F) "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C) and Poly (IC:LC), respectively...
2017: PloS One
Ruijing Liang, Jun Xie, Jun Li, Ke Wang, Liping Liu, Yujie Gao, Mubashir Hussain, Guanxin Shen, Jintao Zhu, Juan Tao
For nanovaccine-based cancer immunotherapy, dendritic cells (DCs) are one of the most powerful antigen presenting cells (APCs) that initiate and promote the maturation of antigen-specific cytotoxic T lymphocytes (e.g., CD8(+) T cells) to induce the local and systemic antitumor immunity and further suppress the tumor metastasis and produce long-term protection against tumor. Thus, the activation and maturation of DCs is the prerequisite for efficient CD8(+) T cell-based antitumor immune responses, which is considered as a primary and promising task for nanovaccine engineering...
September 26, 2017: Biomaterials
Rein Verbeke, Ine Lentacker, Laura Wayteck, Karine Breckpot, Mieke Van Bockstal, Benedicte Descamps, Christian Vanhove, Stefaan C De Smedt, Heleen Dewitte
This study reports on the design of mRNA and adjuvant-loaded lipid nanoparticles for therapeutic cancer vaccination. The use of nucleoside-modified mRNA has previously been shown to improve the translational capacity and safety of mRNA-therapeutics, as it prevents the induction of type I interferons (IFNs). However, type I IFNs were identified as the key molecules that trigger the activation of antigen presenting cells, and as such drive T cell immunity. We demonstrate that nucleoside-modified mRNA can be co-delivered with the clinically approved TLR agonist monophosphoryl lipid A (MPLA)...
November 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
Mahboubeh Ebrahimian, Maryam Hashemi, Mohsen Maleki, Gholamreza Hashemitabar, Khalil Abnous, Mohammad Ramezani, Alireza Haghparast
Strategies to design delivery vehicles are critical in modern vaccine-adjuvant development. Nanoparticles (NPs) encapsulating antigen(s) and adjuvant(s) are promising vehicles to deliver antigen(s) and adjuvant(s) to antigen-presenting cells (APCs), allowing optimal immune responses against a specific pathogen. In this study, we developed a novel adjuvant delivery approach for induction of efficient in vivo immune responses. Polyethylenimine (PEI) was physically conjugated to poly(lactic-co-glycolic) acid (PLGA) to form PLGA/PEI NPs...
2017: Frontiers in Immunology
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