Lipid-Based Particles: Versatile Delivery Systems for Mucosal Vaccination against Infection

Abstract

Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i.e., mucosal surfaces. It is now well documented that immune responses along the genital, respiratory, or gastrointestinal tracts have to be elicited locally to ensure efficient trafficking of effector and memory B and T cells to mucosal tissues. Moreover, needle-free mucosal delivery of vaccines is advantageous in terms of safety, compliance, and ease of administration. However, the quest for mucosal vaccines is challenging due to (1) the fact that Ag sampling has to be performed across the epithelium through a relatively limited number of portals of entry; (2) the deleterious acidic and proteolytic environment of the mucosae that affect the stability, integrity, and retention time of the applied Ags; and (3) the tolerogenic environment of mucosae, which requires the addition of adjuvants to elicit efficient effector immune responses. Until now, only few mucosally applicable vaccine formulations have been developed and successfully tested. In animal models and clinical trials, the use of lipidic structures such as liposomes, virosomes, immune stimulating complexes, gas-filled microbubbles and emulsions has proven efficient for the mucosal delivery of associated Ags and the induction of local and systemic immune reponses. Such particles are suitable for mucosal delivery because they protect the associated payload from degradation and deliver concentrated amounts of Ags via specialized sampling cells (microfold cells) within the mucosal epithelium to underlying antigen-presenting cells. The review aims at summarizing recent development in the field of mucosal vaccination using lipid-based particles. The modularity ensured by tailoring the lipidic design and content of particles, and their known safety as already established in humans, make the continuing appraisal of these vaccine candidates a promising development in the field of targeted mucosal vaccination.

Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

“…Whereas larger particles (more than 500 nm) will be taken up via phagocytosis or pinocytosis and will most likely induce humoral responses. Regarding nasal administration, smaller particle will more likely reach the nasal mucosa while larger particle will be incorporated by respiratory macrophages [ 146 ]. Targeting specific M cell receptors may accelerate the vaccine uptake [ 60 ].…”

Formulation technologies for oral vaccines

“…Successful generation of oral immune responses has been reported in a number of disease models . See Corthésy et al for a general review of lipid‐based particles as mucosal vaccine adjuvants, including the oil droplet approaches described here later .…”

Combined adjuvant-delivery system for new generation vaccine antigens: alliance has its own advantage

“…focal pit to intercalate antigen in the lipid bilayer maintained, depot impact in antigen release, immunogen transferring carrier and adjuvant. The particulate character of virosomes can easily fascinate the APCs such as DCs for attaining immunological benefits [43]. The licensed virosomal vaccine against hepatitis A (Epaxal) and Flu (Inflexal V) have approved the fabulous attributes of virosomes as an adjuvant and carrier system [44] (Table 3).…”