Vaccine delivery alerts innate immune systems for more immunogenic vaccination.
Vaccine delivery alerts innate immune systems for more immunogenic vaccination.
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DOI：
10.1172/jci.insight.144627
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发表时间：
2021-04-08
期刊：
影响因子：
8
通讯作者：
Chen, Xinyuan
中科院分区：
文献类型：
--
作者：
Li, Zhuofan;Cao, Yan;Chen, Xinyuan
疫苗递送技术主要被设计成以最小侵入性将疫苗递送至靶组织，而几乎没有或没有佐剂作用。本研究提出了一种原型激光粉末递送（LPD），具有固有的佐剂效应，可用于更免疫原性的疫苗接种，而无需引入外部佐剂。LPD利用美学消融分数激光产生皮肤微通道以支持高效疫苗递送，同时在微通道周围组织中产生光热应力以促进疫苗接种。在小鼠模型中，与基于针的皮内递送相比，LPD可显著增强2009 H1N1流感疫苗的免疫原性和保护效力。发现消融性分数激光诱导宿主DNA释放，激活含有3个炎性小体的NLR家族pyrin结构域，并刺激IL-1 β释放，尽管它们与激光佐剂效应无关。相反，烧蚀分数激光激活MyD 88介导其佐剂效应的增强抗原摄取，成熟和迁移的树突状细胞。由于微量和持续的疫苗递送，LPD还诱导最小的局部或全身不良反应。我们的数据支持通过有意诱导良好控制的组织应激来提醒先天免疫系统进行更具免疫原性的疫苗接种来开发自佐剂疫苗递送技术。
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-1beta 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.