Abstract

Infectious disease remains a substantial cause of death. To overcome this issue, mucosal vaccine systems are considered to be a promising strategy. Yet, none are approved for clinical use, except for live-attenuated mucosal vaccines, mainly owing to the lack of effective and safe systems to induce antigen-specific immune responses in the mucosal compartment. We have reported that intranasal vaccination of an antigenic protein, with cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl], induced antigen-specific mucosal and systemic antibody responses in mice. However, precise molecular mechanism(s) underlying the mucosal adjuvant effects of cationic liposomes remain to be uncovered. Here, we show that a host double-stranded DNA (dsDNA), released at the site of cationic liposome injection, plays an essential role for the mucosal adjuvanticity of the cationic liposome. Namely, we found that nasal administration of the cationic liposomes induced localized cell death, at the site of injection, resulting in extracellular leakage of host dsDNA. Additionally, in vivo DNase I treatment markedly impaired OVA-specific mucosal and systemic antibody production exerted by cationic liposomes. Our report reveals that host dsDNA, released from local dying cells, acts as a damage-associated molecular pattern that mediates the mucosal adjuvant activity of cationic liposomes.

Highlights

  • Infectious diseases are responsible for a substantial number of deaths, despite developments in modern medicine

  • We investigated the involvement of damage-associated molecular patterns (DAMPs) in antigen-specific antibody responses induced by DOTAP/dendritic cells (DCs)-chol liposomes in both mucosal and systemic compartments in mice

  • Mucosal vaccines microbes, have longonly beena few considered a predominant strategymucosal in overcoming infectious diseases caused by pathogenic live-attenuated and inactivated fatal infectious diseases caused by pathogenic microbes, only a few live-attenuated and inactivated vaccines are utilized in the clinic

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Summary

Introduction

Infectious diseases are responsible for a substantial number of deaths, despite developments in modern medicine. Live-attenuated and/or inactivated vaccines are widely utilized for human clinical use, though they may cause detrimental effects especially in newborns, elders, or immunodeficient patients [1,2]. Emerging mucosal vaccines are considered to be the most promising way to prevent death caused by pathogens because, unlike parenteral vaccinations, mucosal vaccines are capable of inducing specific immune responses to pathogens in Vaccines 2020, 8, 8; doi:10.3390/vaccines8010008 www.mdpi.com/journal/vaccines. No mucosal vaccines have been approved for clinical use except for live-attenuated mucosal vaccines [3,4,5,6]. The development of mucosal adjuvant is crucial, owing to inherently poor immunogenicity of antigens at mucosal sites, such as the nasal route [7]

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