Effective adjuvantation of nanograms of influenza vaccine and induction of cross-protective immunity by physical radiofrequency adjuvant.

Effective adjuvantation of nanograms of influenza vaccine and induction of cross-protective immunity by physical radiofrequency adjuvant.
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DOI:
10.1038/s41598-022-25605-4
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发表时间:
2022-12-08
期刊:
影响因子:
4.6
通讯作者:
Chen, Xinyuan
Chen, Xinyuan
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li, Zhuofan;Kang, Xinliang;Kim, Ki-Hye;Zhao, Yiwen;Li, Yibo;Kang, Sang-Moo;Chen, Xinyuan

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迫切需要新型佐剂来帮助开发针对现有或新出现的传染病的改进或新型疫苗。考虑到常用的明矾和MF59佐剂会诱导组织应激和内源性危险信号释放来介导其佐剂作用,物理方式可用于诱导组织应激和内源性危险信号释放,以增强疫苗诱导的免疫反应。此外,物理佐剂由于其局部作用而不太可能引起显着的全身不良反应。最近,我们发现皮肤的非侵入性射频(RF)预处理可以显着增强小鼠模型中皮内疫苗诱导的免疫反应,包括大流行性流感疫苗、大流行前疫苗和流感内抗原疫苗。物理射频佐剂(RFA)是否可用于加强季节性流感疫苗接种、节省疫苗剂量并诱导交叉保护性免疫,仍有待探索。这项研究发现,物理 RFA 可以显着增强季节性流感疫苗诱导的针对每种病毒株的免疫反应,并在小鼠模型中显着增强低剂量(纳克)H3N2 疫苗诱导的免疫反应和保护。 RFA 还诱导针对异源和异亚型流感病毒的交叉保护性免疫。进一步的研究发现热休克蛋白 70(诱导内源性危险信号)和骨髓分化初级反应 88 接头在 RFA 的剂量节约效应中发挥着至关重要的作用。这些数据有力地支持了物理 RFA 的进一步开发,以促进流感疫苗接种。
Novel adjuvants are highly demanded to aid in development of improved or new vaccines against existing or emerging infectious diseases. Considering commonly used Alum and MF59 adjuvants induce tissue stress and release of endogenous danger signals to mediate their adjuvant effects, physical modalities may be used to induce tissue stress and endogenous danger signal release to enhance vaccine-induced immune responses. Furthermore, physical adjuvants are less likely to induce significant systemic adverse reactions due to their localized effects. Recently we found non-invasive radiofrequency (RF) pretreatment of the skin could significantly enhance intradermal vaccine-induced immune responses in murine models that included pandemic influenza vaccine, pre-pandemic vaccine, and influenza internal antigen vaccine. It remained to be explored whether the physical RF adjuvant (RFA) could be used to boost seasonal influenza vaccination, spare vaccine doses, and induce cross-protective immunity. This study found the physical RFA could significantly enhance seasonal influenza vaccine-induced immune responses against each viral strain and robustly enhance low-dose (nanograms) H3N2 vaccine-induced immune responses and protection in murine models. RFA also induced cross-protective immunity against heterologous and heterosubtypic influenza viruses. Further studies found heat shock protein 70 (inducible endogenous danger signal) and myeloid differentiation primary response 88 adaptor played a crucial role in dose-sparing effects of RFA. These data strongly support further development of the physical RFA to boost influenza vaccination.
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