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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 with 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 inflammasome, and stimulate IL-1\u03b2 release despite 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 microfractional and sustained vaccine delivery. 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