Investigating Prime-Pull Vaccination through a Combination of Parenteral Vaccination and Intranasal Boosting

Abstract

Formulation of inhalable delivery systems containing tuberculosis (TB) antigens to target the site of infection (lungs) have been considered for the development of subunit vaccines. Inert delivery systems such as poly (lactic-co-glycolic acid) (PLGA) are an interesting approach due to its approval for human use. However, PLGA suffers hydrolytic degradation when stored in a liquid environment for prolonged time. Therefore, in this study, nano- and microparticles composed of different PLGA copolymers (50:50, 75:25 and 85:15), sucrose (10% w/v) and L-leucine (1% w/v) encapsulating H56 TB vaccine candidate were produced as dried powders. In vitro studies in three macrophage cell lines (MH-S, RAW264.7 and THP-1) showed the ability of these cells to take up the formulated PLGA:H56 particles and process the antigen. An in vivo prime-pull immunisation approach consisting of priming with CAF01:H56 (2 × subcutaneous (s.c.) injection) followed by a mucosal boost with PLGA:H56 (intranasal (i.n.) administration) demonstrated the retention of the immunogenicity of the antigen encapsulated within the lyophilised PLGA delivery system, although no enhancing effect could be observed compared to the administration of antigen alone as a boost. The work here could provide the foundations for the scale independent manufacture of polymer delivery systems encapsulating antigens for inhalation/aerolisation to the lungs.

Manufacturing Considerations for the Development of Lipid Nanoparticles Using Microfluidics

“…In general, optimal parameters consist of convenient particle size (usually below 100 nm to allow for sterile filtration and effective nucleic acid delivery), adequate composition, high encapsulation efficiencies (>90%), stability upon storage and a reproducible and scalable manufacturing method. Microfluidics has previously been shown to be an effective tool for the manufacture of LNPs [ 15 , 16 , 19 , 20 ], liposomes [ 21 , 22 , 23 ] and polymer-based nanoparticles [ 24 , 25 , 26 ]. However, the literature lacks reports evaluating the effects of the formulation and microfluidic operating parameters on the physicochemical characteristics of the LNPs.…”

Using microfluidics for scalable manufacturing of nanomedicines from bench to GMP: A case study using protein-loaded liposomes

“…Therefore the aim of our work was to compare and map the critical process attributes of both the staggered herringbone mixer that we have previously used (e.g. Anderluzzi and Perrie, 2019;Khadke et al, 2019;Lou et al, 2019;Roces et al, 2019a) with this new toroidal micromixer design and to test the production of liposomes from bench to GMP-scale.…”

Investigating the Impact of Delivery System Design on the Efficacy of Self-Amplifying RNA Vaccines

“…PLGA nanoparticles for nucleic acid delivery have attracted strong interest as an alternative to the commonly used polycationic carriers that can be toxic and/or non-biodegradable [ 74 ]. PLGA has been licensed by the FDA and European Medicines Agency (EMA) for the delivery of therapeutics via subcutaneous, intradermal, intramuscular and mucosal routes [ 77 , 78 ]. PLGA has also been adopted in the manufacturing of biomedical devices like surgical sutures and bone implants [ 79 ].…”