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Fengqiang Cao, Mengmeng Yan, Yijia Liu, Lanxia Liu, Guilei Ma
Cancer vaccines aim to induce a strong major histocompatibility complex class I (MHC-I)-restricted CD8+ cytotoxic T-cell response, which is an important prerequisite for successful cancer immunotherapy. Herein, a hyaluronic acid (HA) and antigen (ovalbumin, OVA)-decorated gold nanoparticle (AuNPs)-based (HA-OVA-AuNPs) vaccine is developed for photothermally controlled cytosolic antigen delivery using near-infrared (NIR) irradiation and is found to induce antigen-specific CD8+ T-cell responses. Chemical binding of thiolated HA and OVA to AuNPs facilitates antigen uptake of dendritic cells via receptor-mediated endocytosis...
March 6, 2018: Advanced Healthcare Materials
Ting Kang, Yukun Huang, Qianqian Zhu, Hao Cheng, Yuanyuan Pei, Jingxian Feng, Minjun Xu, Gan Jiang, Qingxiang Song, Tianze Jiang, Hongzhuan Chen, Xiaoling Gao, Jun Chen
Recent breakthroughs in cancer immunotherapy offer new paradigm-shifting therapeutic options for combating cancer. Personalized therapeutic anti-cancer vaccines training T cells to directly fight against tumor cells endogenously offer tremendous benefits in working synergistically with immune checkpoint inhibitors. Biomimetic nanotechnology offers a versatile platform to boost anticancer immunity by efficiently co-delivering optimized immunogenic antigen materials and adjuvants to antigen presenting cells (APC)...
February 23, 2018: Biomaterials
Liping Qiu, Michael Valente, Yusuf Dolen, Eliezer Jäger, Martin Ter Beest, Liyan Zheng, Carl G Figdor, Martijn Verdoes
The activation of tumor-specific effector immune cells is key for successful immunotherapy and vaccination is a powerful strategy to induce such adaptive immune responses. However, the generation of effective anticancer vaccines is challenging. To overcome these challenges, a novel straight-forward strategy of adjuvant-induced tumor antigen assembly to generate nanovaccines with superior antigen/adjuvant loading efficiency is developed. To protect nanovaccines in circulation and to introduce additional functionalities, a biocompatible polyphenol coating is installed...
March 1, 2018: Small
Xia Dong, Zhiting Sun, Jie Liang, Hai Wang, Dunwan Zhu, Xigang Leng, Chun Wang, Deling Kong, Feng Lv
Accurate and efficient antigen delivery is crucial for inducing a strong and long-term immune response. A visible protein nanovaccine made from antigen could provide a novel and promising technology for secure and efficient delivery of the antigen with imaging visualization. In this study, a functional nanovaccine based on genipin crosslinked ovalbumin (OVA) fluorescent nanoparticles with chitosan (CS-OVA-NPs) was developed. The nanovaccine can carry abundant antigens by self-crosslinking without additional carriers...
February 20, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Jodi L McGill, Sean M Kelly, Pankaj Kumar, Savannah Speckhart, Shannon L Haughney, Jamie Henningson, Balaji Narasimhan, Randy E Sacco
Human respiratory syncytial virus (HRSV) is a leading cause of severe acute lower respiratory tract infection in infants and children worldwide. Bovine RSV (BRSV) is closely related to HRSV and a significant cause of morbidity in young cattle. BRSV infection in calves displays many similarities to RSV infection in humans, including similar age dependency and disease pathogenesis. Polyanhydride nanoparticle-based vaccines (i.e., nanovaccines) have shown promise as adjuvants and vaccine delivery vehicles due to their ability to promote enhanced immunogenicity through the route of administration, provide sustained antigen exposure, and induce both antibody- and cell-mediated immunity...
February 14, 2018: Scientific Reports
F Q Cao, M M Yan, Y J Liu, L X Liu, L Lu, H Wang, Ch Zhang, H F Sun, D L Kong, G L Ma
Herein, the photosensitizer indocyanine green (ICG) is used to induce the self-assembly of antigens to form nanovaccines. Under near-infrared (NIR) laser irradiation, reactive oxygen species can be generated by nanovaccines to disrupt the membranes of endo/lysosomes, which helps to release antigens into the cytosol efficiently, thereby enhancing antigen cross-presentation and anti-cancer immunity. To the best of our knowledge, this study represents the first example of ICG as a biocompatible adjuvant to improve cancer vaccine efficacy...
February 13, 2018: Biomaterials Science
Mi Qi, Xian-En Zhang, Xianxun Sun, Xiaowei Zhang, Yanfeng Yao, Siling Liu, Ze Chen, Wei Li, Zhiping Zhang, Jianjun Chen, Zongqiang Cui
Cross-protective and non-invasively administered vaccines are attractive and highly desired for the control of influenza. Self-assembling nanotechnology provides an opportunity for the development of vaccines with superior performance. In this study, an intranasal nanovaccine is developed targeting the conserved ectodomain of influenza matrix protein 2(M2e). 3-sequential repeats of M2e (3M2e) is presented on the self-assembling recombinant human heavy chain ferritin (rHF) cage to form the 3M2e-rHF nanoparticle...
February 12, 2018: Small
Zahra Sadat Hosseini, Jafar Amani, Fahimeh Baghbani Arani, Shahram Nazarian, Mohammad Javad Motamedi, Fatemeh Shafighian
Purpose: Escherichia coli O157:H7 is one of the most important pathogens which create hemorrhagic colitis and hemolytic uremic syndrome in human. It is one of the most prevalent causes of diarrhea leading to death of many people every year. The first diagnosed gene in the locus of enterocyte effacement pathogenicity island is eae gene. The product of this gene is a binding protein called intimin belonging to the group of external membrane proteins regarded as a good stimulants of the immune system...
January 2018: Clinical and Experimental Vaccine Research
Rajnish Sahu, Richa Verma, Saurabh Dixit, Joseph U Igietseme, Carolyn M Black, Skyla Duncan, Shree R Singh, Vida A Dennis
There is a persisting global burden and considerable public health challenge by the plethora of ocular, genital and respiratory diseases caused by members of the Gram-negative bacteria of the genus Chlamydia. The major diseases are conjunctivitis and blinding trachoma, non-gonococcal urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and interstitial pneumonia. The failures in screening and other prevention programs led to the current medical opinion that an efficacious prophylactic vaccine is the best approach to protect humans from chlamydial infections...
March 2018: Expert Review of Vaccines
Hitesh Kumar Dewangan, Tarun Pandey, Lakshmi Maurya, Sanjay Singh
The present work is focused on the development and evaluation of single dose sustained-release Hepatitis B surface antigen (HBsAg) loaded nanovaccine for Hepatitis B. The conventional treatment suffers from repeated administration and hence requires a booster dose. Therefore, polymeric nanovaccine of HBsAg was developed by double emulsion solvent evaporation technique, utilizing central composite design for formulation optimization. The effects of independent variables (like polymer amount, stabilizer concentration, aqueous/organic phase ratio and homogenizer speed) were also studied on critical quality attributes like particle size and entrapment efficiency...
January 14, 2018: International Journal of Biological Macromolecules
Saurabh Dixit, Rajnish Sahu, Richa Verma, Skyla Duncan, Guillermo H Giambartolomei, Shree R Singh, Vida A Dennis
We previously developed a Chlamydia trachomatis nanovaccine (PPM) by encapsulating a chlamydial M278 peptide within poly(lactic acid)-poly(ethylene glycol) biodegradable nanoparticles that immunopotentiated Chlamydia-specific immune effector responses in mice. Herein, we investigated the mechanistic interactions of PPM with mouse bone marrow-derived dendritic cells (DCs) for its uptake, trafficking, and T cell activation. Our results reveal that PPM triggered enhanced expression of effector cytokines and chemokines, surface activation markers (Cd1d2, Fcgr1), pathogen-sensing receptors (TLR2, Nod1), co-stimulatory (CD40, CD80, CD86) and MHC class I and II molecules...
December 26, 2017: Biomaterials
Xiaoyu Liang, Xuanling Li, Jianwei Duan, Youlu Chen, Xiaoli Wang, Liyun Pang, Deling Kong, Bing Song, Chen Li, Jing Yang
Currently, development of subunit vaccine based on recombinant antigens or peptides has gradually become an important alternative option for traditional vaccine. However, induction of potent immune response with desired efficacy remains a major challenge. The nanoparticle-based antigen delivery system has been considered a potential carrier system to improve the efficacy of subunit vaccine. In the present study, we have designed an immune-stimulatory delivery system by conjugating three-armed PLGA to PEG via the peroxalate ester bond which is sensitive to hydrogen peroxide (H2O2), a major reactive oxygen species (ROS)...
January 11, 2018: Molecular Pharmaceutics
Jinbin Pan, Yaqiong Wang, Cai Zhang, Xiaoyi Wang, Haoyu Wang, Jiaojiao Wang, Yizhong Yuan, Xu Wang, Xuejun Zhang, Chunshui Yu, Shao-Kai Sun, Xiu-Ping Yan
Current antigen-encapsulated multifunctional nanovaccines for oncotherapy suffer from limited antigen loading efficiency, low yield, tedious manufacture, and systemic toxicity. Here, an antigen-directed strategy for the fabrication of multifunctional nanovaccine with ultrahigh antigen loading efficiency in a facile way for tumor photothermal-immunotherapy is shown. As a proof of concept, a model antigen ovalbumin (OVA) is used as a natural carrier to load a representative theranostic agent indocyanine green (ICG)...
January 10, 2018: Advanced Materials
Eva Zupančič, Caterina Curato, Jung-Seok Kim, Eilam Yeini, Ziv Porat, Ana S Viana, Anat Globerson-Levin, Tova Waks, Zelig Eshhar, João N Moreira, Ronit Satchi-Fainaro, Lea Eisenbach, Steffen Jung, Helena F Florindo
Nanoparticulate vaccines are promising tools to overcome cancer immune evasion. However, a deeper understanding on nanoparticle-immune cell interactions and treatments regime are required for optimal efficacy. We provide a comprehensive study of treatment schedules and mode of antigen-association to nanovaccines on the modulation of T cell immunity in vivo, under steady-state and tumor-bearing mice. The coordinated delivery of antigen and two adjuvants (Monophosphoryl lipid A, oligodeoxynucleotide cytosine-phosphate-guanine motifs (CpG)) by nanoparticles was crucial for dendritic cell activation...
January 3, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
Ashley V Kroll, Ronnie H Fang, Yao Jiang, Jiarong Zhou, Xiaoli Wei, Chun Lai Yu, Jie Gao, Brian T Luk, Diana Dehaini, Weiwei Gao, Liangfang Zhang
Anticancer vaccines train the body's own immune system to recognize and eliminate malignant cells based on differential antigen expression. While conceptually attractive, clinical efficacy is lacking given several key challenges stemming from the similarities between cancerous and healthy tissue. Ideally, an effective vaccine formulation would deliver multiple tumor antigens in a fashion that potently stimulates endogenous immune responses against those antigens. Here, it is reported on the fabrication of a biomimetic, nanoparticulate anticancer vaccine that is capable of delivering autologously derived tumor antigen material together with a highly immunostimulatory adjuvant...
December 2017: Advanced Materials
Guizhi Zhu, Geoffrey M Lynn, Orit Jacobson, Kai Chen, Yi Liu, Huimin Zhang, Ying Ma, Fuwu Zhang, Rui Tian, Qianqian Ni, Siyuan Cheng, Zhantong Wang, Nan Lu, Bryant C Yung, Zhe Wang, Lixin Lang, Xiao Fu, Albert Jin, Ido D Weiss, Harshad Vishwasrao, Gang Niu, Hari Shroff, Dennis M Klinman, Robert A Seder, Xiaoyuan Chen
Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund's adjuvant (IFA)...
December 5, 2017: Nature Communications
Hitesh Kumar Dewangan, Tarun Pandey, Sanjay Singh
Chronic Hepatitis B Virus (HBV) infections are severe with weak antiviral immune responses. The lack of an appropriate small animal model for chronic hepatitis, a major hurdle for studying the immunotolerance and immunopathogenesis induced by hepatitis B viral (HBV) infection. In this study, for enhancing the antibody production efficiency the prepared polymeric HBsAg-loaded nanoparticles (nanovaccine) will be tested in immune-deficit mice, which suffer from chronic Hepatitis B virus. Vaccination of Balb/c mice by this prepared nanoparticles that were engrafted with peripheral blood mononuclear cells (PBMCs), which was already lethally irradiated and transplanted by the bone marrow of NOD (knockout mice) mice...
November 27, 2017: Artificial Cells, Nanomedicine, and Biotechnology
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
Guizhi Zhu, Lei Mei, Harshad D Vishwasrao, Orit Jacobson, Zhantong Wang, Yijing Liu, Bryant C Yung, Xiao Fu, Albert Jin, Gang Niu, Qin Wang, Fuwu Zhang, Hari Shroff, Xiaoyuan Chen
Nanomedicines that co-deliver DNA, RNA, and peptide therapeutics are highly desirable yet remain underdeveloped for cancer theranostics. Herein, we report self-assembled intertwining DNA-RNA nanocapsules (iDR-NCs) that efficiently delivered synergistic DNA CpG and short hairpin RNA (shRNA) adjuvants, as well as tumor-specific peptide neoantigens into antigen presenting cells (APCs) in lymph nodes for cancer immunotherapy. These nanovaccines were prepared by (1) producing tandem CpG and shRNA via concurrent rolling circle replication and rolling circle transcription, (2) self-assembling CpG and shRNA into DNA-RNA microflowers, (3) shrinking microflowers into iDR-NCs using PEG-grafted cationic polypeptides, and (4) physically loading neoantigen into iDR-NCs...
November 14, 2017: Nature Communications
Faez Amokrane Nait Mohamed, Abdelmounaim Nouri, Fatima Laraba-Djebari
An attenuated nanovaccine (Nps - V(∗)) has been developed to protect humans from fatal scorpion envenomation in at-risk regions. This study was conducted to evaluate the toxicity and the local reactogenicity of the Nps - V(∗) nanovaccine developed against Androctonus australis hector (Aah) venom. Assessment of the systemic inflammatory response and serum cytokine levels were evaluated in vaccinated mice with 100μg of irradiated Aah venom (V(∗)) encapsulated or not into polymeric calcium-alginate nanoparticles (Nps) and injected by subcutaneous (s...
October 20, 2017: Vaccine
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