scholarly journals Cholesteryl Pullulan Nanoparticles-Encapsulated TNF-α: An Effective Mucosal Vaccine Adjuvant Against Influenza

Author(s):  
Tsunetaka Ohta
mSphere ◽  
2018 ◽  
Vol 3 (4) ◽  
Author(s):  
John D. Clements ◽  
Elizabeth B. Norton

ABSTRACTPerhaps the best-studied mucosal adjuvants are the bacterially derived ADP-ribosylating enterotoxins. This adjuvant family includes heat-labile enterotoxin ofEscherichia coli(LT), cholera toxin (CT), and mutants or subunits of LT and CT. These proteins promote a multifaceted antigen-specific response, including inflammatory Th1, Th2, Th17, cytotoxic T lymphocytes (CTLs), and antibodies. However, more uniquely among adjuvant classes, they induce antigen-specific IgA antibodies and long-lasting memory to coadministered antigens when delivered mucosally or even parenterally. The purpose of this minireview is to describe the general properties, history and creation, preclinical studies, clinical studies, mechanisms of action, and considerations for use of the most promising enterotoxin-based adjuvant to date, LT(R192G/L211A) or dmLT. This review is timely due to completed, ongoing, and planned clinical investigations of dmLT in multiple vaccine formulations by government, nonprofit, and industry groups in the United States and abroad.


2018 ◽  
Vol 46 (sup1) ◽  
pp. 852-860 ◽  
Author(s):  
Wenjing Qu ◽  
Na Li ◽  
Rui Yu ◽  
Wenbao Zuo ◽  
Tingting Fu ◽  
...  

2010 ◽  
Vol 9 (4) ◽  
pp. 431-440 ◽  
Author(s):  
Girishchandra B Patel ◽  
Wangxue Chen

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Daiki Nagatomo ◽  
Madoka Taniai ◽  
Harumi Ariyasu ◽  
Mutsuko Taniguchi ◽  
Miho Aga ◽  
...  

We encapsulated tumor necrosis factor-α(TNF-α), a major proinflammatory cytokine, into cholesteryl pullulan (CHP) to prepare TNF/CHP nanoparticles. In this report, we describe the immune-enhancing capability of the nanoparticles to act as a vaccine adjuvant. TNF/CHP nanoparticles showed excellent storage stability and enhanced host immune responses to external immunogens. The nanoparticles were effective via the nasal route of administration for inducing systemic IgG1as well as mucosal IgA. We applied the nanoparticles in a model experimental influenza virus infection to investigate their adjuvant ability. TNF/CHP nanoparticles combined with a conventional split vaccine protected mice via nasal administration against a lethal challenge of A/PR/8/34 (H1N1) influenza virus. Mechanistic studies showed that the nanoparticles enhanced antigen uptake by dendritic cells (DCs) and moderately induced the expression of inflammation-related genes in nasopharynx lymphoid tissue (NALT), leading to the activation of both B and T cells. Preliminary safety study revealed no severe toxicity to TNF/CHP nanoparticles. Slight-to-moderate influences in nasal mucosa were observed only in the repeated administration and they seemed to be reversible. Our data show that TNF/CHP nanoparticles effectively enhance both humoral and cellular immunity and could be a potential adjuvant for vaccines against infectious diseases, especially in the mucosa.


Vaccine ◽  
2008 ◽  
Vol 26 (46) ◽  
pp. 5778-5783 ◽  
Author(s):  
Naima G. Cortes-Perez ◽  
Luis F. da Costa Medina ◽  
François Lefèvre ◽  
Philippe Langella ◽  
Luis G. Bermúdez-Humarán

2001 ◽  
Vol 167 (6) ◽  
pp. 3398-3405 ◽  
Author(s):  
Allan M. I. Mowat ◽  
Anne M. Donachie ◽  
Sara Jägewall ◽  
Karin Schön ◽  
Björn Löwenadler ◽  
...  

ChemInform ◽  
2010 ◽  
Vol 41 (22) ◽  
pp. no-no
Author(s):  
Hiroyuki Kayamuro ◽  
Yasuo Yoshioka ◽  
Yasuhiro Abe ◽  
Haruhiko Kamada ◽  
Shin-ichi Tsunoda ◽  
...  

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Dool-Ri Oh ◽  
Hu Won Kang ◽  
Jong-Ro Kim ◽  
Sunoh Kim ◽  
In-Kyu Park ◽  
...  

Toll-like receptor (TLR) ligands are being developed for use as vaccine adjuvants and as immunomodulators because of their ability to stimulate innate and adaptive immune responses. Flagellin, a TLR5 ligand, was reported to show potent mucosal vaccine adjuvant activity. To identify ligands that potentiate the adjuvant activity of flagellin, we screened a plant library using HEK293T cells transiently cotransfected with phTLR5 and pNF-κB-SEAP plasmids. The 90% EtOH extract fromCroton tigliumshowed significant NF-κB transactivation in a TLR5-independent manner along with the increase of a flagellin activity. We have studied to characterize an active component fromCroton tigliumand to elucidate the action mechanisms. Phorbol 12-myristate 13-acetate (PMA) was isolated as an active component ofCroton tigliumby activity-guided fractionation, column chromatography, HPLC, NMR, and MS. PMA at a range of nM induced PKC-dependent NF-κB activation and IL-8 production in both TLR5− and TLR5+ assay systems. In in vivo mouse vaccination model, PMA induced antigen-specific IgG and IgA antibody responses and increased IL-12 production corresponding to T cell responses in spleen lymphocytes. These results suggest that PMA would serve as an efficacious mucosal vaccine adjuvant.


2014 ◽  
Vol 42 (15) ◽  
pp. 9996-10004 ◽  
Author(s):  
Emil F. Khisamutdinov ◽  
Hui Li ◽  
Daniel L. Jasinski ◽  
Jiao Chen ◽  
Jian Fu ◽  
...  

Abstract Modulation of immune response is important in cancer immunotherapy, vaccine adjuvant development and inflammatory or immune disease therapy. Here we report the development of new immunomodulators via control of shape transition among RNA triangle, square and pentagon. Changing one RNA strand in polygons automatically induced the stretching of the interior angle from 60° to 90° or 108°, resulting in self-assembly of elegant RNA triangles, squares and pentagons. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-α and IL-6 induction was greatly enhanced in vitro and in animals up to 100-fold, while RNA polygon controls induced unnoticeable effect. The RNA nanoparticles were delivered to macrophages specifically. The degree of immunostimulation greatly depended on the size, shape and number of the payload per nanoparticles. Stronger immune response was observed when the number of adjuvants per polygon was increased, demonstrating the advantage of shape transition from triangle to pentagon.


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