Dataset Information

Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori.

ABSTRACT:

Background

Helicobacter pylori (H. pylori) infection remains a global public health issue, especially in Asia. Due to the emergence of antibiotic-resistant strains and the complexity of H. pylori infection, conventional vaccination is the best way to control the disease. Our previous study found that the N-acetyl-neuroaminyllactose-binding hemagglutinin protein (HpaA) is an effective protective antigen for vaccination against H. pylori infection, and intranasal immunization with the immunodominant HpaA epitope peptide (HpaA 154-171, P22, MEGVLIPAGFIKVTILEP) in conjunction with a CpG adjuvant decreased bacterial colonization in H. pylori-infected mice. However, to confer more robust and effective protection against H. pylori infection, an optimized delivery system is needed to enhance the P22-specific memory T cell response.

Results

In this study, an intranasal nanoemulsion (NE) delivery system offering high vaccine efficacy without obvious cytotoxicity was designed and produced. We found that this highly stable system significantly prolonged the nasal residence time and enhanced the cellular uptake of the epitope peptide, which powerfully boosted the specific Th1 responses of the NE-P22 vaccine, thus reducing bacterial colonization without CpG. Furthermore, the protection efficacy was further enhanced by combining the NE-P22 vaccine with CpG.

Conclusion

This epitope-loaded nanoemulsion delivery system was shown to extend antigen release and elicit potent Th1 response, it is an applicable delivery system for intranasal vaccine against H. pylori.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6339695 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori.

Yang Yun Y Chen Li L Sun Hong-Wu HW Guo Hong H Song Zhen Z You Ying Y Yang Liu-Yang LY Tong Ya-Nan YN Gao Ji-Ning JN Zeng Hao H Yang Wu-Chen WC Zou Quan-Ming QM

Journal of nanobiotechnology 20190119 1

<h4>Background</h4>Helicobacter pylori (H. pylori) infection remains a global public health issue, especially in Asia. Due to the emergence of antibiotic-resistant strains and the complexity of H. pylori infection, conventional vaccination is the best way to control the disease. Our previous study found that the N-acetyl-neuroaminyllactose-binding hemagglutinin protein (HpaA) is an effective protective antigen for vaccination against H. pylori infection, and intranasal immunization with the immu ...[more]

PMID: 30660182

Similar Datasets

Project description:Background:Huperzine A (HupA) is a selective acetylcholinesterase inhibitor used to treat Alzheimer's disease. The existing dosage of HupA lacks brain selectivity and can cause serious side effects in the gastrointestinal and peripheral cholinergic systems. Purpose:The aim of this study was to develop and characterize a HupA nanoemulsion (NE) and a targeted HupA-NE modified with lactoferrin (Lf) for intranasal administration. Methods:The NE was formulated using pseudo-ternary phase diagrams and optimized with response surface methodology. Particle size distribution and zeta potential were evaluated, and transmission electron microscopy was performed. We investigated the transport mechanisms of HupA-NEs into hCMEC/D3 cells, an in vitro model of the blood-brain barrier. HupA-NE, Lf-HupA-NE, and HupA solution were intranasally administered to rats to investigate the brain-targeting effects of these formulations. A drug targeting index (DTI) was calculated to determine brain-targeting efficiency. Results:Optimized HupA-NE had a particle size of 15.24±0.67 nm, polydispersity index (PDI) of 0.128±0.025, and zeta potential of -4.48±0.97 mV. The composition of the optimized HupA-NE was 3.00% isopropyl myristate (IPM), 3.81% Capryol 90, and 40% Cremophor EL + Labrasol. NEs, particularly Lf-HupA-NE, were taken up into hCMEC/D3 cells to a greater extent than pure drug alone. Western blot analysis showed that hCMEC/D3 cells contained P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance associated protein 1 (MRP1) transporters. The likely mechanisms resulting in higher NE transport to the brain were uptake by specific transporters and transcytosis. In vivo, intranasal Lf-HupA-NE significantly enhanced drug delivery to the brain compared to HupA-NE, which was confirmed by differences in pharmacokinetic parameters. The DTI of Lf-HupA-NE (3.2±0.75) demonstrated brain targeting, and the area under the curve for Lf-HupA-NE was significantly higher than that for HupA-NE. Conclusion:Lf-HupA-NE is a promising nasal drug delivery carrier for facilitating delivery of HupA to the central nervous system.

Project description:Helicobacter pylori is a human pathogen that infects almost half of the population. Antibiotic resistance in H. pylori threatens health and increases the demand for prophylactic and therapeutic vaccines. Traditional oral vaccine research faces considerable challenges because of the epithelial barrier, potential enterotoxicity of adjuvants, and the challenging conditions of the gastric environment. We developed an intranasal influenza A virus (IAV) vector vaccine based on two live attenuated influenza viruses with modified acidic polymerase protein (PA) genes encoding the A subunit of H. pylori neutrophil-activating protein (NapA), named IAV-NapA, including influenza virus A/WSN/33 (WSN)-NapA and A/Puerto Rico/8/34 (PR8)-NapA. These recombinant influenza viruses were highly attenuated and exhibited strong immunogenicity in mice. Vaccination with IAV-NapA induced antigen-specific humoral and mucosal immune responses while stimulating robust Th1 and Th17 cell immune responses in mice. Our findings suggest that prophylactic and therapeutic vaccination with influenza virus vector vaccines significantly reduces colonization of H. pylori and inflammation in the stomach of mice.IMPORTANCEHelicobacter pylori is the most common cause of chronic gastritis and leads to severe gastroduodenal pathology in some patients. Many studies have shown that Th1 and Th17 cellular and gastric mucosal immune responses are critical in reducing H. pylori load. IAV vector vaccines can stimulate these immune responses while overcoming potential adjuvant toxicity and antigen dosing issues. To date, no studies have demonstrated the role of live attenuated IAV vector vaccines in preventing and treating H. pylori infection. Our work indicates that vaccination with IAV-NapA induces antigen-specific humoral, cellular, and mucosal immunity, producing a protective and therapeutic effect against H. pylori infection in BALB/c mice. This undescribed H. pylori vaccination approach may provide valuable information for developing vaccines against H. pylori infection.

Project description:Helicobacter pylori (H. pylori) classified as a class I carcinogen by the World Health Organization (WHO) plays an important role in the progression of chronic gastritis and the development of gastric cancer. A major bioactive component of Evodia rutaecarpa, evodiamine, has been known for its anti-bacterial effect and anti-cancer effects. However, the inhibitory effect of evodiamine against H. pylori is not yet known and the inhibitory mechanisms of evodiamine against gastric cancer cells are yet to be elucidated concretely. In this study, therefore, anti-bacterial effect of evodiamine on H. pylori growth and its inhibitory mechanisms as well as anti-inflammatory effects and its mechanisms of evodiamine on H. pylori-induced inflammation were investigated in vitr. Results of this study showed the growth of the H. pylori reference strains and clinical isolates were inhibited by evodiamine. It was considered one of the inhibitory mechanisms that evodiamine downregulated both gene expressions of replication and transcription machineries of H. pylori. Treatment of evodiamine also induced downregulation of urease and diminished translocation of cytotoxin-associated antigen A (CagA) and vacuolating cytotoxin A (VacA) proteins into gastric adenocarcinoma (AGS) cells. This may be resulted from the reduction of CagA and VacA expressions as well as the type IV secretion system (T4SS) components and secretion system subunit protein A (SecA) protein which are involved in translocation of CagA and VacA into host cells, respectively. In particular, evodiamine inhibited the activation of signaling proteins such as the nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and the mitogen-activated protein kinase (MAPK) pathway induced by H. pylori infection. It consequently might contribute to reduction of interleukin (IL)-8 production in AGS cells. Collectively, these results suggest anti-bacterial and anti-inflammatory effects of evodiamine against H. pylori.

Dataset Information

Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori.

Background

Results

Conclusion

Publications

Epitope-loaded nanoemulsion delivery system with ability of extending antigen release elicits potent Th1 response for intranasal vaccine against Helicobacter pylori.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets