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Zongmin Zhao, Kristen Powers, Yun Hu, Michael Raleigh, Paul Pentel, Chenming Zhang
Although vaccination is a promising way to combat nicotine addiction, most traditional hapten-protein conjugate nicotine vaccines only show limited efficacy due to their poor recognition and uptake by immune cells. This study aimed to develop a hybrid nanoparticle-based nicotine vaccine with improved efficacy. The focus was to study the impact of hapten density on the immunological efficacy of the proposed hybrid nanovaccine. It was shown that the nanovaccine nanoparticles were taken up by the dendritic cells more efficiently than the conjugate vaccine, regardless of the hapten density on the nanoparticles...
January 27, 2017: Biomaterials
Santosh Dhakal, Jonathan Goodman, Kathryn Bondra, Yashavanth S Lakshmanappa, Jagadish Hiremath, Duan-Liang Shyu, Kang Ouyang, Kyung-Il Kang, Steven Krakowka, Michael J Wannemuehler, Chang Won Lee, Balaji Narasimhan, Gourapura J Renukaradhya
We have recently demonstrated the effectiveness of an influenza A virus (IAV) subunit vaccine based on biodegradable polyanhydride nanoparticles delivery in mice. In the present study, we evaluated the efficacy of ∼200nm polyanhydride nanoparticles encapsulating inactivated swine influenza A virus (SwIAV) as a vaccine to induce protective immunity against a heterologous IAV challenge in pigs. Nursery pigs were vaccinated intranasally twice with inactivated SwIAV H1N2 (KAg) or polyanhydride nanoparticle-encapsulated KAg (KAg nanovaccine), and efficacy was evaluated against a heterologous zoonotic virulent SwIAV H1N1 challenge...
January 20, 2017: Vaccine
Maria Agallou, Maritsa Margaroni, Evita Athanasiou, Dimitra K Toubanaki, Katerina Kontonikola, Konstantina Karidi, Olga Kammona, Costas Kiparissides, Evdokia Karagouni
BACKGROUND: Through their increased potential to be engaged and processed by dendritic cells (DCs), nanovaccines consisting of Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with both antigenic moieties and adjuvants are attractive candidates for triggering specific defense mechanisms against intracellular pathogens. The aim of the present study was to evaluate the immunogenicity and prophylactic potential of a rationally designed multi-epitope peptide of Leishmania Cysteine Protease A (CPA160-189) co-encapsulated with Monophosphoryl lipid A (MPLA) in PLGA NPs against L...
January 2017: PLoS Neglected Tropical Diseases
Flavia Fontana, Mohammad-Ali Shahbazi, Dongfei Liu, Hongbo Zhang, Ermei Mäkilä, Jarno Salonen, Jouni T Hirvonen, Hélder A Santos
Immunoadjuvant porous silicon (PSi)-based nanovaccines are prepared by nanoprecipitation in a glass capillary microfluidics device. Vesicles, derived from cancer cell membranes encapsulating thermally oxidized PSi nanoparticles or PSi-polymer nanosystems binding a model antigen, are biocompatible over a wide range of concentrations, and show immunostimulant properties in human cells, promoting the expression of co-stimulatory signals and the secretion of pro-inflammatory cytokines.
December 23, 2016: Advanced Materials
Bo Li, Michael Siuta, Vanessa Bright, Dmitry Koktysh, Brittany K Matlock, Megan E Dumas, Meiying Zhu, Alex Holt, Donald Stec, Shenglou Deng, Paul B Savage, Sebastian Joyce, Wellington Pham
The present study investigated the immunoenhancing property of our newly designed nanovaccine, that is, its ability to induce antigen-specific immunity. This study also evaluated the synergistic effect of a novel compound PBS-44, an α-galactosylceramide analog, in boosting the immune response induced by our nanovaccine. The nanovaccine was prepared by encapsulating ovalbumin (ova) and an adjuvant within the poly(lactic-co-glycolic acid) nanoparticles. Quantitative analysis of our study data showed that the encapsulated vaccine was physically and biologically stable; the core content of our nanovaccine was found to be released steadily and slowly, and nearly 90% of the core content was slowly released over the course of 25 days...
2016: International Journal of Nanomedicine
Liang Zhao, Antonino S Cavallaro, David Wibowo, Bing Zhang, Jun Zhang, Neena Mitter, Chengzhong Yu, Chun-Xia Zhao, Anton P J Middelberg
Anaplasma marginale is a devastating tick-borne pathogen causing anaplasmosis in cattle and results in significant economic loss to the cattle industry worldwide. Currently, there is no widely accepted vaccine against A. marginale. New generation subunit vaccines against A. marginale, which are much safer, more efficient and cost-effective, are in great need. The A. marginale outer membrane protein VirB9-1 is a promising antigen for vaccination. We previously have shown that soluble recombinant VirB9-1 protein can be expressed and purified from Escherichia coli and induce a high level of humoral and cellular immunity in mice...
January 3, 2017: Vaccine
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...
January 2017: 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...
November 15, 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
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