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.
Highlights
Vaccination is considered as one of the most successful medical actions and has greatly contributed to the improvement of world health
Vaccination has led to the control of several diseases and has demonstrated substantial technological progresses, humans still suffer from infections leading to death and increasing health costs
Many infectious diseases for which the development of effective vaccines is urgently needed include those transmitted through various mucosal routes that affect the gastrointestinal tract (E. coli, Salmonella, Shigella, Vibrio cholerae, H. pylori), the respiratory tract (Influenza, M. tuberculosis, respiratory syncitial virus) or are sexually transmitted (HIV, Chlamydia) [15]
Summary
Vaccination is considered as one of the most successful medical actions and has greatly contributed to the improvement of world health. In order to achieve the induction of protective anti-pathogen humoral and cellular responses at the relevant mucosal surfaces, the choice of the most potent administration route has to be carefully considered by taking into account the physiological and immunological features of the different target tissues [15] These aspects and the strategies to target vaccines to the portals of entry across the epithelium and increase the efficiency of delivery will first be discussed. Activation of NKT cells by administration of α-galactosylceramide is of interest for nasal, oral, and sublingual vaccination due to its ability to enhance immunogenicity of different mucosal vaccine formulations [138,139,140] All these adjuvants can be incorporated within lipid-based particles or associated at their surface depending on the localization of their cognate receptor in target cells.
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