Abstract
Despite significant modern medicine progress, having an infectious disease is a major risk factor for humans. Mucosal vaccination is now widely considered as the most promising strategy to defeat infectious diseases; however, only live-attenuated and inactivated mucosal vaccines are used in the clinical field. To date, no subunit mucosal vaccine was approved mainly because of the lack of safe and effective methodologies to either activate or initiate host mucosal immune responses. We have recently elucidated that intranasal administration of enzymatically polymerised caffeic acid potentiates antigen-specific mucosal and systemic antibody responses in mice. However, our earlier study has not confirmed whether these effects are specific to the polymer synthesised from caffeic acid. Here, we show that enzymatically polymerised polyphenols (EPPs) from various phenolic compounds possess mucosal adjuvant activities when administered nasally with an antigen to mice. Potentiation of antigen-specific immune responses by all EPPs tested in this study showed no clear difference among the precursors used. We found that intranasal administration of ovalbumin as the antigen, in combination with all enzymatically polymerised polyphenols used in this study, induced ovalbumin-specific mucosal IgA in the nasal cavity, bronchoalveolar lavage fluid, vaginal fluids, and systemic IgG, especially IgG1, in sera. Our results demonstrate that the mucosal adjuvant activities of polyphenols are not limited to polymerised caffeic acid but are broadly observable across the studied polyphenols. These properties of polyphenols may be advantageous for the development of safe and effective nasal vaccine systems to prevent and/or treat various infectious diseases.
Highlights
Infectious diseases are a major risk factor in humans and are difficult to eradicate
We examined the mucosal adjuvant effects of polymerised trans-ferulic acid (pFA)
OVA plus pFA or p-coumaric acid (pCoA) induced high levels of OVA-specific mucosal IgA as well as BALF IgG compared with mice immunised with OVA alone; the levels were similar to those generated by polymerised caffeic acid (pCA) (Fig 2)
Summary
Infectious diseases are a major risk factor in humans and are difficult to eradicate. No subunit mucosal vaccine has been approved, mainly because of the lack of safe and effective methodologies to either activate and/or initiate host mucosal immune responses by using mucosal adjuvants [11,12] or to deliver the microbial antigens to mucosal dendritic cells (mDCs) by means of antigen delivery vehicles [13,14]. Liposomes, nanogels, and bacterial components, which are utilised when some bacteria intrude the host tissues, have been reported to act as antigen delivery systems for mDCs [20,21,22,23,24] Such systems may cause side effects due to the presence of antigenic and toxic molecules largely derived from microbes. A safer and more effective system to promote antigen-specific immune responses in mucosal surfaces is needed for the successful development of mucosal vaccines
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