Tannic acid-Aluminum (Ⅲ) coordination-enabled microcapsules for pH-responsive protein vaccine delivery / 国际生物医学工程杂志

Objective To establish a simple and gentle antigen loading method to prepare pH-responsive and biodegradable microcapsules for efficient antigen delivery.Methods Co-precipitation method was used to embed chicken egg albumin (OVA) in CaCO3 particles.Then,TA and Al (Ⅲ) were coated on the surface of CaCO3 particles template by metal-organic coordination bonds.The CaCO3 template was removed from disodium edetate to obtain TA-Al(Ⅲ) microcapsules carrying OVA,i.e.the OVA@TA-Al(Ⅲ) microcapsules.The microcapsules were characterized by field emission scanning electron microscopy,transmission electron microscopy,X-ray energy spectrometry and atomic force microscopy.The distribution of OVA in the microcapsules was observed by laser scanning confocal microscopy.The cumulative release rate of OVA in the microcapsules at different pH phosphate buffers was also investigated.The cytotoxicity of the microcapsules on immortalized mouse dendritic cells DC2.4 was observed by thiazolyl blue assay.The phagocytosis of the microcapsules by DC2.4 cells was observed by laser scanning confocal microscopy.Results The results of field emission scanning electron microscope and transmission electron microscopy showed that the OVA@TA-Al(Ⅲ) microcapsules have a intact structure and a hollow and collapsed appearance with a diameter of about 4 μm.X-ray energy spectrum showed that there are five kinds of elements,i.e.C,O,Al,Si and Na,in the microcapsules,among which C,Al and some O elements belong to the composition of the microcapsules.Atomic force microscopy showed that the microcapsules have an ultra-thin wall,and the walls of the microcapsules are uniform in thickness (about 16 nm).Laser scanning confocal microscopy showed that OVAs were evenly distributed in the CaCO3 particles.Moreover,the pH sensitivity of the coordination bond makes the OVA@TA-Al(Ⅲ) microcapsules have pH responsiveness.In addition,the microcapsules also have good biocompatibility,and the DC2.4 cells also have good phagocytic ability to the microcapsules.Conclusion A simple and gentle antigen-encapsuling method was developed to achieve effective antigen payload and pH responsive delivery.The prepared microcapsules are expected to be used as a novel antigen delivery vector for clinical research.

Live bacterial vaccine vectors: An overview

Genetically attenuated microorganisms, pathogens, and some commensal bacteria can be engineered to deliver recombinant heterologous antigens to stimulate the host immune system, while still offering good levels of safety. A key feature of these live vectors is their capacity to stimulate mucosal as well as humoral and/or cellular systemic immunity. This enables the use of different forms of vaccination to prevent pathogen colonization of mucosal tissues, the front door for many infectious agents. Furthermore, delivery of DNA vaccines and immune system stimulatory molecules, such as cytokines, can be achieved using these special carriers, whose adjuvant properties and, sometimes, invasive capacities enhance the immune response. More recently, the unique features and versatility of these vectors have also been exploited to develop anti-cancer vaccines, where tumor-associated antigens, cytokines, and DNA or RNA molecules are delivered. Different strategies and genetic tools are constantly being developed, increasing the antigenic potential of agents delivered by these systems, opening fresh perspectives for the deployment of vehicles for new purposes. Here we summarize the main characteristics of the different types of live bacterial vectors and discuss new applications of these delivery systems in the field of vaccinology.

Evaluation of systemic and mucosal immune responses in mice administered with novel recombinant Salmonella vaccines for avian pathogenic Esherichia coli / 대한수의학회지

Avian pathogenic Escherichia coli (APEC) is a causative agent for a number of extra intestinal diseases and account for significant losses to the poultry industry. Since protective immunity against APEC is largely directed to virulence antigens, we have individually expressed four different viulence antigens, papA, papG, IutA, and CS31A, using an attenuated Salmonella Typhimurium and a plasmid pBB244. Following oral immunization of mice with combination of two or four of these strains, serum IgG and mucosal IgA responses were elicited against each antigen represented in the mixture. The antigen-specific mucosal IgA responses were significantly higher in the group of mice immunized with the heat-labile Escherichia coli enterotoxin B subunit (LTB) strain than those in the group of mice immunized without the LTB strain. While, there was no significant difference between these two groups in antigen-specific serum IgG responses. The results showed that LTB could act as mucosal immune adjuvant. To assess the nature of immunity, the distribution of antigen-specific IgG isotypes was analyzed. All groups promoted Th1-type immunity as determined by the IgG2a/IgG1 ratio. Thus, our findings provided evidence that immunization with a combination of several vaccine strains is one of the strategies of developing effective vaccines against APEC.

Advances on The Novel Drug Deliver System:Bacterial Ghost / 生物化学与生物物理进展

Bacterial ghost is intact bacterial envelope which is lysised by the lysis geneE of PhiX174. It can be used as vaccine directly. Foreign antigen can be targeted into outer membrane, inner membrane or the periplasmic space of bacterial, as a result, a recombinant bacterial ghost is constructed. Bacterial ghost, as a novel drug delivery system, is becoming more and more concerned, which can deliver DNA and protein vaccine or other drugs in order to have a better immune responses and therapeutic effects.