Technological Approaches for Improving Vaccination Compliance and Coverage

Abstract

Vaccination has been well recognised as a critically important tool in preventing infectious disease, yet incomplete immunisation coverage remains a major obstacle to achieving disease control and eradication. As medical products for global access, vaccines need to be safe, effective and inexpensive. In line with these goals, continuous improvements of vaccine delivery strategies are necessary to achieve the full potential of immunisation. Novel technologies related to vaccine delivery and route of administration, use of advanced adjuvants and controlled antigen release (single-dose immunisation) approaches are expected to contribute to improved coverage and patient compliance. This review discusses the application of micro- and nano-technologies in the alternative routes of vaccine administration (mucosal and cutaneous vaccination), oral vaccine delivery as well as vaccine encapsulation with the aim of controlled antigen release for single-dose vaccination.

Keywords: adjuvants; compliance; cutaneous vaccination; microfluidics; mucosal vaccination; vaccine delivery.

Figure 1

Advanced vaccination technologies and strategies for improving compliance and coverage. Key drug delivery systems to overcome barriers associated with each administration route are presented: (a) nasal and pulmonary immunisation using particulate delivery systems such as lipid-based systems (liposomes or nanocapsules), polymeric nanoparticles (NPs), gold NPs, self-assembled NPs (e.g., chitosan), dendrimers, and micelles; (b) oral immunisation using delivery systems such as hydrogels, scaffolds, and particles (nano- and microparticles); (c) cutaneous immunisation can be performed using microneedles, scaffolds, hydrogels, nano- and microparticles; (d) advanced technologies for improving vaccine manufacture and delivery, such as single-dose immunisation using polymeric NPs, and vaccine encapsulation using emulsions or microfluidics systems. Figure prepared using BioRender.

Figure 2

Proposed mechanism of the SmPill^® minispheres and the induction of intestinal vaccine-specific immune responses: 1. The enteric coating of SmPill^® minispheres remains intact in the acidic environment of the stomach protecting the payload; 2. On exiting the stomach and the passage into the increasing pH of the small intestine, the enteric coating begins to degrade, exposing the gelatine core and releasing the oil droplets containing the vaccine antigen (e.g., whole-cell killed bacteria) and the solubilised adjuvant (e.g., α-GalCer); 3. The payload is gradually released in the small intestine and the antigen/adjuvant can cross the intestinal epithelium (e.g., through M cells) where the presentation of processed whole-cell killed bacteria and α-GalCer by DCs to T cells and invariant natural killer T (iNKT) cells occurs, respectively. This leads to B cell activation; 4. B cells undergo affinity maturation, class switch recombination and differentiation into plasma cells, which enter into the circulation and home back to the lamina propria where antigen-specific IgA secretion occurs; 5. Upon infection with viable bacteria, sIgA transported into the intestinal lumen can neutralise the bacteria. Figure prepared using BioRender.

Figure 3

Core:shell microparticles prepared by two different manufacture methods. Confocal images of (a) the microparticles by the water-in-oil-in-water (W/O/W) method, core: sodium alginate 75–200 kDa (NovaMatrix^®), shell: PLGA–rhodamine (50:50 30 kDa); (b) the microparticles by the W/O/W method, core: sodium alginate labelled with calcein, shell as in (a). Fluorescent microscopy images (40 × magnification) of (c) the thin shell microparticles by the microfluidics method, core: dextran-FITC 70 kDa, shell: PLGA resomer R502 (50:50 7–17 kDa); (d) thick shell microparticles by the microfluidics method (same parameters as in (c)).

Figure 4

Double emulsion template formation by successive intersections in microfluidic chip.