Transcutaneous Immunization System Using a Hydrotropic Formulation Induces a Potent Antigen-Specific Antibody Response

Abstract

BackgroundTranscutaneous immunization (TCI) is a novel vaccination strategy, which is expected to have therapeutic applications. However, to develop effective TCI systems, a simple, non-invasive and safe transdermal formulation is required. This study developed a novel TCI system utilizing the co-administration of a liposoluble absorption enhancer, propylene glycol monocaprylate (PGMC) and hydrosoluble protein antigen without pretreatment of any typical adjuvants and disruption of the skin. Novel transdermal formulations were also prepared with sodium salicylate (NaSal) as a hydrotropic agent to improve the solubility of poorly water-soluble substances.Methodology/Principal FindingsThe TCI system, which used a transdermal formulation containing hen lysozyme (HEL) and PGMC, solubilized with NaSal, resulted in a substantial HEL-specific antibody response in an HEL dose-dependent manner even in the absence of potent adjuvants, such as cholera toxin (CT). We also investigated whether NaSal activates antigen-presenting cells in vitro to clarify the mechanisms of antibody production by the hydrotropic formulation. NaSal enhanced the expression of MHC class II molecules and increased the production of IL-12 and TNF-α in dendritic cells, which were stimulated by lipopolysaccharide in vitro, indicating that NaSal had an effective adjuvant-like property. Moreover, the use of NaSal in the TCI system did not induce an HEL-specific, IgE-dependent anaphylactic reaction.Conclusion/SignificanceOur TCI system using a hydrotropic formulation effectively and safely induced the intended immune response, and this system thus represents a new advantageous method that will result in improved TCI strategies.

Transcutaneous antigen delivery system

“…Co-application of adjuvants with antigens is required to elicit successful immune responses by TCI (21 , 52) . Successful adjuvants for vaccines include bacterial toxins, microbial products, cytokines, liposomes, oligodeoxynucleotides, and mineral salts (53) . Of these, the most commonly used adjuvants, including alum, monophosphoryl lipid A, and an MF59 emulsion, are undesirable for TCI, likely due to their limited transport across the stratum corneum (4 , 54) .…”

“…These may in turn promote the activation LCs and their migration to regional lymph nodes. Novel TCI system induced an antigen-specific antibody response in the presence of sodium salicylate even without adjuvants, such as CT (53) . Sodium salicylate had an adjuvant-like effect via activation of antigen presenting cells.…”