Mannose derivative and lipid A dually decorated cationic liposomes as an effective cold chain free oral mucosal vaccine adjuvant-delivery system

2014 ◽  
Vol 88 (1) ◽  
pp. 194-206 ◽  
Author(s):  
Ning Wang ◽  
Ting Wang ◽  
Meiling Zhang ◽  
Ruonan Chen ◽  
Ruowen Niu ◽  
...  
2010 ◽  
Vol 9 (4) ◽  
pp. 431-440 ◽  
Author(s):  
Girishchandra B Patel ◽  
Wangxue Chen

2020 ◽  
Vol 8 (8) ◽  
pp. 1102
Author(s):  
Ken Yoshii ◽  
Koji Hosomi ◽  
Atsushi Shimoyama ◽  
Yunru Wang ◽  
Haruki Yamaura ◽  
...  

Effective and safe vaccine adjuvants are needed to appropriately augment mucosal vaccine effects. Our previous study demonstrated that lipopolysaccharide (LPS) from Peyer’s patch resident Alcaligenes stimulated dendritic cells to promote the production of mucosal immunity-enhancing cytokines (e.g., IL-6 and BAFF), thus enhancing antigen-specific immune responses (including IgA production and Th17 responses) without excessive inflammation. Here, we chemically synthesized Alcaligenes lipid A, the biologically active part of LPS, and examined its efficacy as a nasal vaccine adjuvant for the induction of protectively immunity against Streptococcus pneumoniae infection. Mice were nasally immunized with pneumococcal surface protein A (PspA) as a vaccine antigen for S. pneumoniae, together with Alcaligenes lipid A. Alcaligenes lipid A supported the generation of high levels of PspA-specific IgA and IgG responses through the augmentation of germinal center formation in the nasopharynx-associated lymphoid tissue and cervical lymph nodes (CLNs). Moreover, Alcaligenes lipid A promoted PspA-specific CD4+ Th17 responses in the CLNs and spleen. Furthermore, neutrophils were recruited to infection sites upon nasal infection and synchronized with the antigen-specific T and B cell responses, resulting in the protection against S. pneumoniae infection. Taken together, Alcaligenes lipid A could be applied to the prospective adjuvant to enhance nasal vaccine efficacy by means of augmenting both the innate and acquired arms of mucosal immunity against respiratory bacterial infection.


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 ◽  
...  

Vaccines ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 8
Author(s):  
Rui Tada ◽  
Akihiro Ohshima ◽  
Yuya Tanazawa ◽  
Akari Ohmi ◽  
Saeko Takahashi ◽  
...  

Infectious disease remains a substantial cause of death. To overcome this issue, mucosal vaccine systems are considered to be a promising strategy. Yet, none are approved for clinical use, except for live-attenuated mucosal vaccines, mainly owing to the lack of effective and safe systems to induce antigen-specific immune responses in the mucosal compartment. We have reported that intranasal vaccination of an antigenic protein, with cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl], induced antigen-specific mucosal and systemic antibody responses in mice. However, precise molecular mechanism(s) underlying the mucosal adjuvant effects of cationic liposomes remain to be uncovered. Here, we show that a host double-stranded DNA (dsDNA), released at the site of cationic liposome injection, plays an essential role for the mucosal adjuvanticity of the cationic liposome. Namely, we found that nasal administration of the cationic liposomes induced localized cell death, at the site of injection, resulting in extracellular leakage of host dsDNA. Additionally, in vivo DNase I treatment markedly impaired OVA-specific mucosal and systemic antibody production exerted by cationic liposomes. Our report reveals that host dsDNA, released from local dying cells, acts as a damage-associated molecular pattern that mediates the mucosal adjuvant activity of cationic liposomes.


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