EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
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2011
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IF 3.291
Tianyi Wang,Meijuan Zou,Haitao Jiang,Zhaoshuai Ji,Ping Gao,Gang Cheng
The purpose of this study is to develop a novel kind of adjuvant for oral vaccine delivery. In order to effectively prevent the degradation of antigens in the gastrointestinal tract and optimize the uptake for M cells, a novel kind of hydrophobic carbon nanoparticle (C1) with the size of 470 nm was synthesized by taking silica as a template and sucrose as a carbon source. Notably, there were large mesopores and macropores mainly of 40–60 nm, which made it to be excellent candidate as an antigen carrier. C1 was characterized using SEM, TEM and nitrogen adsorption. Following oral immunization with BSA loaded in C1, the IgG titer reached to a level almost equal to that of parenteral administration of antigen emulsified in Freund’s complete adjuvant (FCA). Mucosal IgA was also detected in intestinal, salivary and vaginal secretions, suggesting an effective stimulation of mucosal immune response. Besides, both T-helper 1 and T-helper 2 (Th1 or Th2) mediated responses were induced. We believe that the research will help in the design of novel vaccine adjuvant for improvement their potential on modulation of immune response.
研究领域:
生物医学工程
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免疫学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2025
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IF 12.9
Wen Guo,Zhiqi Wang,Rubing Xue,Xinyue Zhang,Qinfu Zhao,Yikun Gao,Siling Wang,Yuling Mao
Weak response is the bottleneck for subunit prophylactic vaccines to trigger efficient immunization. The emergence of highly effective adjuvants will revolutionize. Considering that genomic epigenetic reprogramming plays an important role in the immune response, we herein present an minimalist epigenetic nano-adjuvant gMSN constructed of β-glucan-modified functional mesoporous silica (MSN), which we term as OVA/gMSN after loaded with the model antigen ovalbumin (OVA). Oral administration of OVA/gMSN ensures that enough antigen reach dendritic cells (DCs) in intestinal mucosal lymphoid follicles via intestinal M cells while relying on gMSN to exhibit good adjuvant properties to trigger an effective systemic co-mucosal immune response. gMSN upregulates genes associated with aerobic glycolysis, promoting metabolic reprogramming in DCs and enhancing the expression of genes related to DC activation, cross-presentation, maturation, and migration. Simultaneously, it increases the accumulation of key epigenetic markers H3K27ac, H3K4me1, and H3K4me3. ATAC-seq results reveal enhanced chromatin accessibility of key immune genes, such as Il2rα1, Il18r1, and Cd83, in gMSN-treated DCs. This integrative molecular mechanism demonstrates that gMSN induces epigenomic remodeling in DCs after oral administration, showcasing the potential of combining epigenetic adjuvants and nanotechnology in oral vaccine design, and providing new directions and a theoretical basis for vaccine adjuvant development.
研究领域:
免疫学
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纳米医学
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疫苗学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2012
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IF 3.35
Tianyi Wang,Haitao Jiang,Qinfu Zhao,Siling Wang,Meijuan Zou,Gang Cheng
Three different kinds of silica (S2, S1 and SBA-15) with different particle sizes (130, 430 nm and 1–2 μm) and different pore characteristics (i.e. pore size and shape) were developed as oral vaccine immunological adjuvants and the relationship between the silica architecture and immunological properties was investigated. The silica particles were characterized using SEM, TEM and nitrogen adsorption. Model antigen bovine serum albumin (BSA) was successfully entrapped into the silica pores to produce a sustained release vaccine delivery system. Compared with the responsiveness induced by parenteral administration of BSA emulsified in Freund's complete adjuvant (FCA), oral immunization with the silica/BSA formulation produced a stimulated humoral and mucosal (sIgA) response. The IgG and IgA titers induced by loading BSA was as follows: S1 > S2 > SBA-15. The highest IgG and IgA titers of S1 were attributed to its large honeycombed pores and the optimal particle diameter of 430 nm. The corresponding IgG1 and IgG2a titers were also investigated to confirm that BSA loaded in nanoparticles by oral immunization can induce both T-helper 1- and T-helper 2- (Th1 or Th2) mediated responses. We believe that the results of our research will open up new avenues for the formulation of oral vaccines.
研究领域:
免疫学
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纳米医学
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疫苗学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR PROBES
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2021
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IF 2.365
Weibin Zhang,Chunhua Zhu,Hongshu Chi,Xiaodong Liu,Hui Gong,Anhua Xie,Weiqiang Zheng,Jia Chen,Na Zhang,Yunkun Wu
Mesoporous silica nanoparticles (MSNs) have been used in the field of biomedicine as antigen carriers and adjuvants for protective antigens. In the present study, an oral nanovaccine against Vibrio alginolyticus was prepared employing MSNs as carriers. The uptake of the dihydrolipoamide dehydrogenase (DLDH) antigens in the intestine of large yellow croaker was evaluated using an immunohistochemistry assay. Additionally, the effects of the nanovaccine on the early immune response in large yellow croaker were investigated via oral vaccination. The presence of the antigens was detected in the mucosa and lamina propria of the foregut , midgut, and hindgut of large yellow croaker at 3 h following oral immunization. The expression levels of cytokines (i.e., lysozyme , IFN-γ, IFITM , TNF-α, IL-1β, IL-2, IL-4, IL-10, and IL-13) in the intestine, spleen, and head kidney tissues of large yellow croaker before and after the immune challenge were determined via RT-qPCR assay. The obtained results revealed that the expression levels of lysozyme, IFN-γ, IFITM, TNF-α, IL-1β, IL-2, IL-4, IL-10, and IL-13 in the intestine and head kidney of the vaccinated large yellow croaker, as well as the expression of lysozyme, IL-1β, and IL-10 in the spleen, exhibited time-dependent oscillation regulation patterns. Notably, the nanovaccine immunization could induce early (6 h) and high expression of IFN-γ in the spleen and kidney tissues after the bacterial infection. The current study supplements the available data on the early immune response to fish nanovaccines. It also provides a valuable theoretical basis for the future development of large yellow croaker oral vaccines.
研究领域:
水产养殖学
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免疫学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2015
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IF 8.557
Lei Zhang,Zhanzhuang Zeng,Chaohua Hu,Susan L. Bellis,Wendi Yang,Yintao Su,Xinyan Zhang,Yunkun Wu
Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly( d , l -lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia , an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae , a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination.
研究领域:
疫苗学
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免疫学
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水产养殖
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微生物学
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产品关联
DOI
PubMed
高影响因子
VETERINARY RESEARCH
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2025
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IF 3.5
Su Kai,Ren Jing,Zhang Yanan,Yuan Chen,Wang Yawen,Yang Liu,Fu Lizhi,Fan Tingli,Song Qinye
Porcine epidemic diarrhea (PED), a highly contagious intestinal disease caused by PEDV, threatens newborn piglets and causes enormous losses in the swine industry. Intestinal mucosal immunity is vital for defense against PEDV. Chitosan (CS), a mucin-adhesive biodegradable polysaccharide, has emerged as a promising mucosal vaccine delivery vector and antigen adjuvant. To develop a PEDV mucosal vaccine, we prepared S1-CS nanoparticles (NPs) loaded with the S1 domain of the PEDV spike (S) protein. We evaluated their ability to induce mucosal immune responses in mice via different inoculation routes and to confer immune protection in piglets after oral inoculation. The results showed that S1-CS NPs exhibited no cytotoxicity and remained stable in simulated gastric fluid in vitro. Compared with oral administration, intramuscular inoculation of S1-CS NPs induced higher levels of PEDV-specific serum IgG in mice. However, PEDV-specific IgA was detected only in the serum and intestinal lavage fluid of orally vaccinated mice. Oral administration also elicited higher IFN-γ levels than intramuscular injection, suggesting stronger activation of cellular immunity. In piglets, oral S1-CS NPs induced serum neutralizing antibodies and IgA responses in both serum and intestinal mucosa, increased the number of IgA-secreting cells in the intestine, reduced viremia and virus shedding, and improved intestinal villus morphology. These findings indicate that the S1-CS NPs developed in this study represent promising candidates for an oral mucosal PEDV vaccine.
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Chunhua Zhu,Na Zhang,Dingding Jing,Xiaodong Liu,Zhanzhuang Zeng,Jingjing Wang,Fangnan Xiao,Hong Zhang,Hongshu Chi,Chunhe Wan,Pingdong Lin,Hui Gong,Yunkun Wu
Streptococcus agalactiae causes systemic disease in a variety of wild and farmed fish, resulting in high levels of morbidity and mortality, as well as serious economic losses to the Nile tilapia aquaculture industry. The development of economic and applicable oral vaccines is therefore urgently needed for the sustainable development of Nile tilapia aquaculture. In this study, mesoporous silica nanoparticles (MSNs) were fabricated using sol–gel synthesis technology, and the antigens of surface immunogenic protein (Sip) was loaded into MSNs to develop a nanovaccine MSNs-Sip@HP55. The results showed that the prepared nanovaccine exhibited pH-controlled release, which could survive in the simulated gastric environment (pH 1.5), and release antigens in the simulated intestinal environment at pH 7.4. The nanovaccine could induce innate and adaptive immune responses in Nile tilapia. When the challenge doses were 1.5 × 10 6 , 1.18 × 10 6 , and 0.88 × 10 6 CFU/mL, the relative protection rates in immunized Nile tilapia were 63.33 %, 64.23 %, and 76.31 %, respectively. Taken together, the nanovaccine exhibited a high antigen utilization rate and was easily administered orally via feeding, which could protect Nile tilapia against challenge with S. agalactiae in large-scale farms. Oral vaccine based on MSNs carriers is a potentially promising strategy for the development of fish vaccines.
研究领域:
水产养殖
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疫苗学
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纳米技术
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免疫学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
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2021
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IF 7.561
Zhang Weibin,Zhu Chunhua,Xiao Fangnan,Liu Xiaodong,Xie Anhua,Chen Fangman,Dong Panpan,Lin Pingdong,Zheng Chenyang,Zhang Hong,Gong Hui,Wu Yunkun
The development of effective vaccines and delivery systems in aquaculture is a long-term challenge for controlling emerging and reemerging infections. Cost-efficient and advanced nanoparticle vaccines are of tremendous applicability in prevention of infectious diseases of fish. In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of Vibrio alginolyticus were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined in vitro. Further, the vaccine immune effects were evaluated in large yellow croaker via oral administration. In vitro studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and released under artificial intestinal fluid environment. In vitro cytotoxicity assessment demonstrated the vaccines within 120 μg/ml have good biocompatibility for large yellow croaker kidney cells. Our data confirmed that the nanoparticle vaccine in vivo could elicit innate and adaptive immune response, and provide good protection against Vibrio alginolyticus challenge. The MSN delivery system prepared may be a potential candidate carrier for fish vaccine via oral administration feeding. Further, we provide theoretical basis for developing convenient, high-performance, and cost-efficient vaccine against infectious diseases in aquaculture.
研究领域:
水产养殖
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纳米技术
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免疫学
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兽医学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Hongyan Lu,Yikun Gao,Jianmin Chen,Jing Chai,Ansheng Li,Tongtong Sun,Yuling Mao,Ye He,Qinfu Zhao,Jinghai Zhang,Siling Wang
Oral vaccines hold great promise for preventing major infectious diseases, but their development is limited by various gastrointestinal tract (GIT) barriers and the low proportion of intestinal microfold (M) cells. Here, inspired by the specific absorption pathway of dietary fat, a novel bionic intestinal lymphatic delivery system based on large mesoporous silica nanoparticles (LMSN) was developed for oral delivery of H1N1 influenza split vaccine (SV). Encouragingly, LMSN with triglyceride biomimetic structure and encapsulated by double-end palmitic acid esterified PEG (PEG-DP), namely [email protected] , exhibited high intestinal epithelium permeability and excellent lymphatic targeting ability. Additionally, TGLMSN, which acting as both antigen carrier and adjuvant, significantly enhanced the ability of SV to stimulate dendritic cells maturation. The results demonstrated that [email protected] vigorously augmented SV-induced antigen-specific systemic and mucosal immunity, compared to oral SV alone. To our knowledge, this is the first study to customize mesoporous silica nanocarriers to load SV and deliver vaccines to mesenteric lymph nodes (MLNs) mainly through the intestinal epithelium cells (IECs) pathway rather than M cells route alone. This work will not only improve the existing influenza vaccination methods, but also open up a new avenue for the design of vaccines against pathogens infected via mucosal route.
研究领域:
药学
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免疫学
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纳米技术
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病毒学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yiduo Liu,Meizhen Long,Yuanzhi Wang,Zhengmin Liang,Yuhui Dong,Mengjin Qu,Xin Ge,Yue Nan,Yulan Chen,Xiangmei Zhou
Vaccination is the most effective method for preventing infectious diseases. Oral vaccinations have attracted much attention due to the ability to boost intestinal and systemic immunity. The focus of this study was to develop a poly (lactide- co -glycolide) acid (PLGA)-based ternary polyelectrolyte complex (PEC) with chitosan, sodium alginate, and transmembrane peptides R8 for the delivery of antigen proteins. In this study, the antigen protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis (MAP) antigens HBHA, Ag85B, and Bfra, was combined with R8 to generate self-assembled conjugates. The results showed that PEC presented a cross-linked reticular structure to protect the encapsulated proteins in the simulated gastric fluid. Then, the nanocomposite separated into individual nanoparticles after entering the simulated intestinal fluid. The ternary PEC with R8 promoted the in vivo uptake of antigens by intestinal lymphoid tissue. Moreover, the ternary PEC administered orally to mice promoted the secretion of specific antibodies and intestinal mucosal IgA. In addition, in the mouse models of MAP infection, the ternary PEC enhanced splenic T cell responses, thus reducing bacterial load and liver pathology score. These results suggested that this ternary electrolyte complex could be a promising delivery platform for oral subunit vaccine candidates, not limited to MAP infection.
研究领域:
疫苗学
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免疫学
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药学
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微生物学
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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