Polymeric Caffeic Acid Is a Safer Mucosal Adjuvant That Augments Antigen-Specific Mucosal and Systemic Immune Responses in Mice

Abstract

Infections remain a major threat to human lives. To overcome the threat caused by pathogens, mucosal vaccines are considered a promising strategy. However, no inactivated and/or subunit mucosal vaccine has been approved for human use, largely because of the lack of a safe and effective mucosal adjuvant. Here, we show that enzymatically synthesized polymeric caffeic acid (pCA) can act as a potent mucosal adjuvant in mice. Intranasal administration of ovalbumin (OVA) in combination with pCA resulted in the induction of OVA-specific mucosal IgA and serum IgG, especially IgG1. Importantly, pCA was synthesized from caffeic acid and horseradish peroxidase from coffee beans and horseradish, respectively, which are commonly consumed. Therefore, pCA is believed to be a highly safe material. In fact, administration of pCA did not show distinct toxicity in mice. These data indicate that pCA has merit for use as a mucosal adjuvant for nasal vaccine formulations.

Role of Interleukin-6 in the Antigen-Specific Mucosal Immunoglobulin A Responses Induced by CpG Oligodeoxynucleotide-Loaded Cationic Liposomes

“…Nasal-associated lymphoid tissue (NALT) and nasal passages were prepared as previously described [20,21]. Mice that were nasally immunized with CpG ODN-loaded cationic liposomes (10 µg CpG ODN/mouse), OVA (5 µg/mouse), or both (10 µg CpG ODN and 5 µg OVA/mouse) were sacrificed by cervical dislocation, and their NALTs and nasal passages were harvested.…”

“…OVA-specific antibody titers were evaluated by ELISA, as described earlier [20]. Briefly, a 96-well Nunc MaxiSorp plate (Thermo Scientific, Waltham, MA, USA) was coated with 1.25 µg of OVA (Sigma-Aldrich, St. Louis, MO, USA) in 0.1 M carbonate buffer (pH 9.5) overnight at 4 • C. The plate was then washed with PBS containing 0.05% Tween 20 (PBST) and blocked with 1% bovine serum albumin (BSA; FUJIFILM Wako Pure Chemical Industries) containing PBST (BPBST) at 37 • C for 60 min.…”

Polymeric Caffeic Acid Acts as a Nasal Vaccine Formulation against Streptococcus pneumoniae Infections in Mice

“…In a previous study, we have reported that intranasal administration of pCA with ovalbumin (OVA), as a model antigen, enhanced OVA-specific antibody production in the mucosal and systemic compartments [25,26]. In this study, we aimed to develop a nasal vaccine against pneumococcal infection using pCA.…”

“…This method resulted in the induction of a higher titer of antigen-specific mucosal and systemic antibody responses in mice. Since intranasal administration of pCA does not exert any toxicity in mice, pCA maybe useful to the development of a safe mucosal vaccine system [25,26]. Further, the sources of CA and HRP are coffee beans and horseradish, respectively, which are easily available.…”

Plant Phenolics as Pathogen-Carrier Immunogenicity Modulator Haptens

“…Studies involving phenylpropanoids and coumarin derivatives report caffeic acid as a safe mucosal adjuvant that augments antigen-specific mucosal and systemic immune responses in mice [ 38 ]; cinnamic acid enhances the immunity and upregulates TLR-4 expression by human monocytes…”