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 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-1β 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. 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.
Highlights
Vaccine delivery technologies are often designed to deliver vaccines to target tissues without causing significant tissue stress or patient discomfort
Using ovalbumin (OVA) and influenza pandemic 2009 H1N1 vaccine as models, we found laser-based powder delivery (LPD) could induce more potent immune responses than needle-based ID delivery in murine models
Molecular adjuvantation mechanisms were explored, and we found MyD88 played a crucial role in laser adjuvant effects, while host DNA, NLR family pyrin domain containing 3 (NLRP3) inflammasome, and IL-1β mainly mediated laser-induced local inflammation
Summary
Vaccine delivery technologies are often designed to deliver vaccines to target tissues without causing significant tissue stress or patient discomfort. In the late 18th century, needles, lancets, and knives were used to disrupt superficial skin to deposit smallpox vaccine, the first vaccine in human history [1]. Syringes and needles were first fabricated in the mid–19th century, and their manufacturing and design were gradually improved over time. Disposable syringes and needles were fabricated in the mid–20th century to reduce needle reuse–associated disease dissemination and have since been the major device used in vaccine delivery. To overcome some drawbacks of needle-based injection delivery, such as needlestick injuries and sharps waste, needle-free Jet Injectors (PharmaJet, Bioject) were developed to deliver high-speed fine-stream liquid vaccines into the muscular tissue [4,5,6,7]
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