Abstract
BackgroundThe respiratory illnesses caused by influenza virus can be dramatically reduced by vaccination. The current trivalent inactivated influenza vaccine is effective in eliciting systemic virus-specific antibodies sufficient to control viral replication. However, influenza protection generated after parenteral immunization could be improved by the induction of mucosal immune responses.Methodology/Principal FindingsTranscutaneous immunization, a non-invasive vaccine delivery method, was used to investigate the quality, duration and effectiveness of the immune responses induced in the presence of inactivated influenza virus co-administered with retinoic acid or oleic acid. We observed an increased migration of dendritic cells to the draining lymph nodes after dermal vaccination. Here we demonstrate that this route of vaccine delivery in combination with certain immunomodulators can induce potent immune responses that result in long-term protective immunity. Additionally, mice vaccinated with inactivated virus in combination with retinoic acid show an enhanced sIgA antibody response, increased number of antibody secreting cells in the mucosal tissues, and protection from a higher influenza lethal dose.Conclusions/SignificanceThe present study demonstrates that transdermal administration of inactivated virus in combination with immunomodulators stimulates dendritic cell migration, results in long-lived systemic and mucosal responses that confer effective protective immunity.
Highlights
Influenza infection and related complications result in thousands of hospitalizations and deaths worldwide every year
Humoral response enhancement by immunomodulators We investigated whether mice transcutaneously immunized with influenza virus generated antibody titers similar to those observed after an influenza viral infection
The present report demonstrates the potential of retinoic acid in combination with cholera toxin as potent immunomodulators in the protective responses induced by transcutaneous immunization with whole inactivated influenza virus
Summary
Influenza infection and related complications result in thousands of hospitalizations and deaths worldwide every year. The TIV induces mainly systemic strain-specific humoral responses while the intranasally administered live attenuated influenza vaccine generates mucosal humoral responses, but its use is limited to people between the ages of 2–49. Alternative vaccine formulations, adjuvantation and routes of delivery are being investigated to create a more efficacious vaccine that would induce long-lived mucosal and systemic immune responses with broader cross-protection. The skin is an immunologically active organ[3] where large numbers of antigen presenting cells (APCs), mainly Langerhans cells and dermal dendritic cells, reside. These populations form an integral part of the innate immune system, which upon antigen stimulation can prime and provide an amplified signal to the cells of the adaptive immune system[4]. Influenza protection generated after parenteral immunization could be improved by the induction of mucosal immune responses
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