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Nicole Mohr, Cinja Kappel, Stefan Kramer, Matthias Bros, Stephan Grabbe, Rudolf Zentel
BACKGROUND: Successful tumor immunotherapy depends on the induction of strong and sustained tumor antigen-specific immune responses by activated antigen-presenting cells (APCs) such as dendritic cells (DCs). Since nanoparticles have the potential to codeliver tumor-specific antigen and DC-stimulating adjuvant in a DC-targeting manner, we wanted to assess the suitability of mannosylated HPMA-LMA block polymers for immunotherapy. MATERIALS & METHODS: Fluorescence-labeled block copolymer micelles derived from P(HPMA)-block-P(LMA) copolymers and according statistical copolymers were synthesized via RAFT polymerization, and loaded with the APC activator L18-MDP...
October 2016: Nanomedicine
Zongmin Zhao, Yun Hu, Reece Hoerle, Meaghan Devine, Michael Raleigh, Paul Pentel, Chenming Zhang
Traditional hapten-protein conjugate nicotine vaccines have shown less than desired immunological efficacy due to their poor recognition and internalization by immune cells. We developed a novel lipid-polymeric hybrid nanoparticle-based nicotine vaccine to enhance the immunogenicity of the conjugate vaccine, and studied the influence of particle size on its immunogenicity and pharmacokinetic efficacy. The results demonstrated that the nanovaccines, regardless of size, could induce a significantly stronger immune response against nicotine compared to the conjugate vaccine...
August 9, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Flavia Fontana, Dongfei Liu, Jouni Hirvonen, Hélder A Santos
The application of nanotechnology to the treatment of cancer or other diseases has been boosted during the last decades due to the possibility to precise deliver drugs where needed, enabling a decrease in the drug's side effects. Nanocarriers are particularly valuable for potentiating the simultaneous co-delivery of multiple drugs in the same particle for the treatment of heavily burdening diseases like cancer. Immunotherapy represents a new concept in the treatment of cancer and has shown outstanding results in patients treated with check-point inhibitors...
July 29, 2016: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
Carlota A Cunha-Matos, Owain R Millington, Alastair W Wark, Michele Zagnoni
Nanomaterials are increasingly being developed for applications in biotechnology, including the delivery of therapeutic drugs and of vaccine antigens. However, there is a lack of screening systems that can rapidly assess the dynamics of nanoparticle uptake and their consequential effects on cells. Established in vitro approaches are often carried out on a single time point, rely on time-consuming bulk measurements and are based primarily on populations of cell lines. As such, these procedures provide averaged results, do not guarantee precise control over the delivery of nanoparticles to cells and cannot easily generate information about the dynamics of nanoparticle-cell interactions and/or nanoparticle-mediated compound delivery...
August 16, 2016: Lab on a Chip
Lanlan Liu, Huqiang Yi, Ce Wang, Huamei He, Ping Li, Hong Pan, Nan Sheng, Manyi Ji, Lintao Cai, Yifan Ma
Immunosuppressive tumor-associated dendritic cells (TADCs) are potential targets for cancer therapy. However, their poor responsiveness to TLR stimulation is a major obstacle for achieving successful cancer immunotherapy. In the current study, we reported a dysregulated miR-148a/DNA methyltransferase (DNMT)1/suppressor of cytokine signaling (SOCS)1 axis as a unique mechanism for dampened TLR stimulation in TADCs. The results showed that aberrantly elevated miR-148a in bone marrow-derived TADC (BM-TADC) abolished polyinosinic-polycytidylic acid (poly I:C) or LPS-induced dendritic cell maturation through directly suppressing DNMT1 gene, which consequently led to the hypomethylation and upregulation of SOCS1, the suppressor of TLR signaling...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Julia E Vela Ramirez, Lorraine T Tygrett, Jihua Hao, Habtom H Habte, Michael W Cho, Neil S Greenspan, Thomas J Waldschmidt, Balaji Narasimhan
Biodegradable polymeric nanoparticle-based subunit vaccines have shown promising characteristics by enhancing antigen presentation and inducing protective immune responses when compared with soluble protein. Specifically, polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have been shown to successfully encapsulate and release antigens, activate B and T cells, and induce both antibody- and cell-mediated immunity towards a variety of immunogens. One of the characteristics of strong thymus-dependent antibody responses is the formation of germinal centers (GC) and the generation of GC B cells, which is part of the T helper cell driven cellular response...
June 2016: Journal of Biomedical Nanotechnology
Yuan Qian, Honglin Jin, Sha Qiao, Yanfeng Dai, Chuan Huang, Lisen Lu, Qingming Luo, Zhihong Zhang
The design of peptide-based subunit vaccine formulations for the direct delivery of tumor antigen peptides (Aps) to dendritic cells (DCs) localized within draining lymph nodes (DLNs) is challenging. Mature DCs (mDCs) are abundantly distributed within DLNs but have dramatically reduced endocytic uptake and antigen-processing abilities, so their role as potential vaccine targets has been largely overlooked. Here we report an ultra-small biocompatible nanovaccine (α-Ap-FNP) functionalized by avidly targeting delivery of Ap via the scavenger receptor class B1 (SR-B1) pathway to mDCs...
May 5, 2016: Biomaterials
Christopher P Karch, Peter Burkhard
Vaccines have been the single most significant advancement in public health, preventing morbidity and mortality in millions of people annually. Vaccine development has traditionally focused on whole organism vaccines, either live attenuated or inactivated vaccines. While successful for many different infectious diseases whole organisms are expensive to produce, require culture of the infectious agent, and have the potential to cause vaccine associated disease in hosts. With advancing technology and a desire to develop safe, cost effective vaccine candidates, the field began to focus on the development of recombinantly expressed antigens known as subunit vaccines...
May 5, 2016: Biochemical Pharmacology
Liang Zhao, Donna Mahony, Antonino S Cavallaro, Bing Zhang, Jun Zhang, James R Deringer, Chun-Xia Zhao, Wendy C Brown, Chengzhong Yu, Neena Mitter, Anton P J Middelberg
Anaplasma marginale is the most prevalent tick-borne livestock pathogen and poses a significant threat to cattle industry. In contrast to currently available live blood-derived vaccines against A. marginale, alternative safer and better-defined subunit vaccines will be of great significance. Two proteins (VirB9-1 and VirB9-2) from the Type IV secretion system of A. marginale have been shown to induce humoral and cellular immunity. In this study, Escherichia coli were used to express VirB9-1 and VirB9-2 proteins...
2016: PloS One
Faez Amokrane Nait Mohamed, Fatima Laraba-Djebari
To enhance humoral defense against diseases, vaccine formulation is routinely prepared to improve immune response. Studies in nanomaterials as a carrier of vaccine delivery are promising and interesting. In this study, attenuated Androctonus australis hector (Aah) venom and its toxic fraction were encapsulated into different formulations inside calcium-alginate nanoparticles (Ca-Alg Nps), and used as a vaccine delivery system against scorpion envenomation. Ca-Alg Nps were prepared by ionic gelation and characterized...
May 23, 2016: Vaccine
Lanxia Liu, Fengqiang Cao, Xiaoxuan Liu, Hai Wang, Chao Zhang, Hongfan Sun, Chun Wang, Xigang Leng, Cunxian Song, Deling Kong, Guilei Ma
Here, we investigated the use of hyaluronic acid (HA)-decorated cationic lipid-poly(lactide-co-glycolide) acid (PLGA) hybrid nanoparticles (HA-DOTAP-PLGA NPs) as vaccine delivery vehicles, which were originally developed for the cytosolic delivery of genes. Our results demonstrated that after the NPs uptake by dendritic cells (DCs), some of the antigens that were encapsulated in HA-DOTAP-PLGA NPs escaped to the cytosolic compartment, and whereas some of the antigens remained in the endosomal/lysosomal compartment, where both MHC-I and MHC-II antigen presentation occurred...
May 18, 2016: ACS Applied Materials & Interfaces
Nirmal Marasini, Ashwini K Giddam, Khairunnisa A Ghaffar, Michael R Batzloff, Michael F Good, Mariusz Skwarczynski, Istvan Toth
AIM: To develop an oral nanovaccine delivery system for lipopeptide-based vaccine candidate against group A Streptococcus. MATERIALS & METHODS: Lipid-core peptide-1-loaded nanoliposomes were prepared as a template and coated with opposite-charged polyelectrolytes to produce particles with size <200 nm. Efficacy of this oral nanovaccine delivery system was evaluated in mice model. RESULTS: Polymer-coated liposomes produced significantly higher antigen-specific mucosal IgA and systemic IgG titers in comparison to vaccine formulated with a strong mucosal adjuvant upon oral immunization in mice...
May 2016: Nanomedicine
Zichao Luo, Ce Wang, Huqiang Yi, Ping Li, Hong Pan, Lanlan Liu, Lintao Cai, Yifan Ma
No abstract text is available yet for this article.
September 10, 2015: Journal of Controlled Release: Official Journal of the Controlled Release Society
Guizhi Zhu, Yijing Liu, Xiangyu Yang, Young-Hwa Kim, Huimin Zhang, Rui Jia, Hsien-Shun Liao, Albert Jin, Jing Lin, Maria Aronova, Richard Leapman, Zhihong Nie, Gang Niu, Xiaoyuan Chen
Cancer evolves to evade or compromise the surveillance of the immune system, and cancer immunotherapy aims to harness the immune system in order to inhibit cancer development. Unmethylated CpG dinucleotide-containing oligonucleotides (CpG), a class of potent adjuvants that activate the toll-like receptor 9 (TLR9) located in the endolysosome of many antigen-presenting cells (APCs), are promising for cancer immunotherapy. However, clinical application of synthetic CpG confronts many challenges such as suboptimal delivery into APCs, unfavorable pharmacokinetics caused by limited biostability and short in vivo half-life, and side effects associated with leaking of CpG into the systemic circulation...
March 28, 2016: Nanoscale
Leticia H Higa, Laura Arnal, Mónica Vermeulen, Ana Paula Perez, Priscila Schilrreff, Cecilia Mundiña-Weilenmann, Osvaldo Yantorno, María Elena Vela, María José Morilla, Eder Lilia Romero
Total antigens from Leishmania braziliensis promastigotes, solubilized with sodium cholate (dsLp), were formulated within ultradeformable nanovesicles (dsLp-ultradeformable archaeosomes, (dsLp-UDA), and dsLp-ultradeformable liposomes (dsLp-UDL)) and topically administered to Balb/c mice. Ultradeformable nanovesicles can penetrate the intact stratum corneum up to the viable epidermis, with no aid of classical permeation enhancers that can damage the barrier function of the skin. Briefly, 100 nm unilamellar dsLp-UDA (soybean phosphatidylcholine: Halorubrum tebenquichense total polar lipids (TPL): sodium cholate, 3:3:1 w:w) of -31...
2016: PloS One
Karishma T Mody, Donna Mahony, Antonino S Cavallaro, Jun Zhang, Bing Zhang, Timothy J Mahony, Chengzhong Yu, Neena Mitter
No abstract text is available yet for this article.
2016: PloS One
Ane Ruiz-de-Angulo, Aintzane Zabaleta, Vanessa Gómez-Vallejo, Jordi Llop, Juan C Mareque-Rivas
Development of vaccines to prevent and treat emerging new pathogens and re-emerging infections and cancer remains a major challenge. An attractive approach is to build the vaccine upon a biocompatible NP that simultaneously acts as accurate delivery vehicle and radiotracer for PET/SPECT imaging for ultrasensitive and quantitative in vivo imaging of NP delivery to target tissues/organs. Success in developing these nanovaccines will depend in part on having a "correct" NP size and accommodating and suitably displaying antigen and/or adjuvants (e...
January 26, 2016: ACS Nano
Simon H Apte, Rachel J Stephenson, Pavla Simerska, Penny L Groves, Salwa Aljohani, Sharareh Eskandari, Istvan Toth, Denise L Doolan
AIM: Systematically evaluate lipid core peptide vaccine delivery platforms to identify core features promoting strong CD8(+) T-cell responses. MATERIALS & METHODS: Three different self-adjuvanting lipid core peptide nanovaccines each comprising four copies of the dominant ovalbumin CD8(+) T-cell epitope and varying in the utilization of a polylysine or glucose core with 2-amino-hexadecanoic acid (C16) or 2-amino-dodecanoic acid (C12) lipids were synthesized. Vaccines were tested for ability to induce CD8(+) T-cell responses and inhibit tumor growth in vivo...
January 2016: Nanomedicine
Karishma T Mody, Donna Mahony, Antonino S Cavallaro, Jun Zhang, Bing Zhang, Timothy J Mahony, Chengzhong Yu, Neena Mitter
Bovine Viral Diarrhoea Virus (BVDV) is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV) based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2) antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0...
2015: PloS One
Diana Boraschi, Paola Italiani
In the last years, nanotechnologies have raised great interest because of the potential applications of engineered nanoparticles in nanomedicine (i.e., in vaccination, in diagnostic imaging procedures, and as therapeutic drug delivery systems). The use of nanoparticles in medicine has brought about the issue of their interaction with the immune system for two main reasons: first, understanding how long nanomedicines could persist in the organism and exert their beneficial effects before being recognized and eliminated by our defensive systems; second, understanding how the immune responses can be modulated by nanoparticles in order to obtain optimal effects...
2015: Vaccines
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