Mucosal and systemic immune responses following mucosal immunisation of tetanus toxoid entrapped in lipid nanoparticles prepared by microwave reactor.

In this study, the use of a microwave reactor, which allowed high input of energy into a pressurised system in a short period of time, was investigated for preparation of lipid nanoparticles (LNPs). The aim was to optimise the formulation process by reducing manufacturing time. Two types of LNPs were prepared; non-ionic surfactant vesicles (NISV) and bilosomes (modified NISV incorporating bile salts), with a model antigen (tetanus toxoid, TT) and the immune response induced after mucosal (nasal and oral, respectively) administration was assessed. The TT loaded LNPs were characterised in terms of particle size, size distribution, morphology, and entrapment efficiency. Immunisation was evaluated by lethal challenge with tetanus toxin in an animal model. The efficiency of vaccination was evaluated by measuring the anti-TT IgG antibody levels in the vaccinated animals. Bilosomes formed by this method showed an immunogen entrapment efficiency of ∼30% which was significantly (p < 0.05) higher than entrapment efficiency in the NISV. The percentage of animals that survived when challenged with tetanus toxin correlated with the level of IgG determined in the serum of mice immunised with LNPs by the mucosal route. Moreover, there were significant (p < 0.05) differences between orally and nasally immunised groups. Animal groups immunised bilosomes via the oral route showed the highest level of IgG (1.2 ± 0.13) compared to the positive control, LN + Xn, and no immunised group. Similarly, groups immunised via the nasal route showed significantly (p < 0.0001) higher titres compared with the control group. Mucosal TT was capable of inducing systemic specific IgG anti-TT responses that were higher than the parenteral vaccine.

Translational modifications to improve vaccine efficacy in an oral influenza vaccine.

Oral vaccination using protein antigens is complicated by the degradative effects of the inhospitable conditions in the gastrointestinal tract, such as low pH and digestive enzymes, nescessitating protection and effective delivery of the antigen. The bilosome is a lipid-based, vesicle delivery system incorporating bile salts, which is believed to protect the antigen from degradation, and has been shown to induce significant antibody responses when delivered orally with various vaccines. In translational research, from laboratory bench to industrial scale-up, it is necessary to optimise the manufacturing process in order to improve efficiency and simplify production, giving a more economical end-product. In this study we tested two simplified production methods (3-step and 1-step) along with two different storage methods (lyophilised and non-lyophilised), as well as looking at the effect of buffer pH. The formulations were assessed in a murine system for immunogenicity, alongside characterisation in terms of size and antigen entrapment, with the stability of these aspects assessed with respect to time. Both lyophilised and non-lyophilised 3-step formulations induced significant IgG1, IgG2a and IgA titres, with the lyophilised version showing stable size and antigen entrapment up to 9months.

Health Economic Analysis of Access Site Practice in England During Changes in Practice: Insights From the British Cardiovascular Interventional Society.

BACKGROUND: Transradial access (TRA) for percutaneous coronary intervention (PCI) is associated with a reduced risk of mortality compared with transfemoral access, access site-related bleeding complications, and shorter length of stay. The budget impact from a healthcare system that has largely transitioned to TRA for PCI has not been previously published. METHODS AND RESULTS: Data from 323 656 patients undergoing PCI between 2010 and 2014 were obtained from the British Cardiovascular Intervention Society database. Costs for TRA and transfemoral access PCI were estimated based on procedure cost, length of stay, and differences in the rates of complications (major bleeding and vascular complications). In the base case, a propensity-matched data set between transfemoral access and TRA was used to directly compare the cost per PCI, whereas in the real-world analysis, the full data set was used. Across all indications and all years, TRA offered an average cost saving of £250.59 per procedure (22% reduction) versus transfemoral access with the majority of cost saving derived from reduced length of stay (£190.43) rather than direct costs of complications (£3.71). In the real-world analysis, adoption of TRA was estimated to have provided cost savings of £13.31 million across England between 2010 and 2014; however, if operators in all regions had adopted TRA at the rate of the region with the highest utilization, cost savings of £33.40 million could have been achieved. CONCLUSIONS: The transition to TRA in England has been associated with significant cost savings across the national healthcare system, in addition to the well-established clinical benefits.