Li et al. introduced a laser-based vaccine delivery platform that utilizes skin microchannels (MCs) generated by an aesthetic laser and delivery of powdered immunogen (laser-based powder delivery; LPD). Murine responses (antibodies or protection against influenza challenge) elicited using immunogen with adjuvant were no greater than responses elicited by LPD alone; adjuvanticity was provided without the need for adjuvants in vaccine formulations. Laser-based delivery enhanced DC function, induced local inflammation, and activated known mediators of adjuvanticity. Experiments using knockout mice showed that response enhancement was mediated through MyD88.
Contributed by Margot O’Toole
ABSTRACT: Vaccine delivery technologies are mainly designed to minimally invasively deliver vaccines to target tissues with little or no adjuvant effects. This study presents a prototype laser-based powder delivery (LPD) with inherent adjuvant effects for more immunogenic vaccination without incorporation of external adjuvants. LPD takes advantage of aesthetic ablative fractional laser to generate skin microchannels to support high-efficient vaccine delivery and at the same time creates photothermal stress in microchannel-surrounding tissues to boost vaccination. LPD could significantly enhance pandemic influenza 2009 H1N1 vaccine immunogenicity and protective efficacy as compared to needle-based intradermal delivery in murine models. The ablative fractional laser was found to induce host DNA release, activate NLR family pyrin domain containing 3 (NLRP3) inflammasome, and stimulate interleukin 1_ release despite of their dispensability for laser adjuvant effects. Instead, the ablative fractional laser activated MyD88 to mediate its adjuvant effects by potentiation of antigen uptake, maturation, and migration of dendritic cells. LPD also induced minimal local or systemic adverse reactions due to the micro-fractional and sustained vaccine delivery. Our data support the development of self-adjuvanted vaccine delivery technologies by intentional induction of well-controlled tissue stress to alert innate immune systems for more immunogenic vaccination.