Exposure of low-temperature plasma after vaccination in tongue promotes systemic IgM induction against spike protein of SARS-CoV-2
Exposure of low-temperature plasma after vaccination in tongue promotes systemic IgM induction against spike protein of SARS-CoV-2
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DOI：
10.1080/10715762.2023.2190486
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发表时间：
2023-01
影响因子：
3.3
通讯作者：
Kotaro Sato;Kouki Fujii;Hiromasa Tanaka;M. Hori;H. Hibi;S. Toyokuni
中科院分区：
文献类型：
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作者：
Kotaro Sato;Kouki Fujii;Hiromasa Tanaka;M. Hori;H. Hibi;S. Toyokuni
自2020年以来，COVID-19一直处于大流行状态，并持续产生新变体。SARS-CoV-2的细胞受体是血管紧张素转换酶2 (ACE2)，其中跨膜丝氨酸蛋白酶2 （TMPRSS2）对病毒内化至关重要。我们最近报道了ACE2和TMPRSS2在人和小鼠口腔中的大量表达。因此，口腔可能是COVID-19感染的大门。在这里，我们承诺评估是否在舌头接种疫苗比皮下注射有任何优点。低温等离子体（LTP）是物质的第四种物理状态，电离高于气体，但在体温下。LTP提供复杂的化学反应，最终在界面上提供氧化和/或亚硝化应力。据报道，ltp相关的细胞死亡可导致细胞凋亡和/或铁下垂。然而，关于LTP暴露后免疫原性保留的数据很少。因此，我们研究了在6周龄雄性BALB/c小鼠舌部注射锁眼帽贝血青素（KLH）或SARS-CoV-2刺突蛋白后暴露LTP的影响，并与皮下接种进行了比较。虽然LTP不会改变舌头中ACE2和TMPRSS2的表达，但在舌头接种后反复暴露LTP可显著促进第11天全身和特异性IgM的产生。相反，皮下接种KLH后反复暴露LTP可减少全身IgM的产生。值得注意的是，舌注射在KLH病例中产生了显著更高的IgM和IgG滴度。综上所述，LTP可显著增强舌注射后IgM的体液免疫。舌头接种疫苗可能是一种获得即时免疫的新策略。
Abstract COVID-19 has been pandemic since 2020 with persistent generation of new variants. Cellular receptor for SARS-CoV-2 is angiotensin-converting enzyme 2 (ACE2), where transmembrane serine protease-2 (TMPRSS2) is essential for viral internalization. We recently reported abundant expression of ACE2 and TMPRSS2 in the oral cavity of humans and mice. Therefore, oral cavity may work for COVID-19 infection gates. Here we undertook to evaluate whether vaccination in the tongue harbors any merit in comparison to subcutaneous injection. Low-temperature plasma (LTP) is the fourth physical state of matters with ionization above gas but at body temperature. LTP provides complex chemistry, eventually supplying oxidative and/or nitrosative stress on the interface. LTP-associated cellular death has been reported to cause apoptosis and/or ferroptosis. However, there is few data available on immunogenicity retention after LTP exposure. We therefore studied the effect of LTP exposure after the injection of keyhole limpet hemocyanin (KLH) or spike 2 protein of SARS-CoV-2 to the tongue of six-week-old male BALB/c mice, compared to subcutaneous vaccination. Whereas LTP did not change the expression of ACE2 and TMPRSS2 in the tongue, repeated LTP exposure after tongue vaccination significantly promoted systemic and specific IgM production at day 11. In contrast, repeated LTP exposure after subcutaneous vaccination of KLH decreased systemic IgM production. Of note, tongue injection produced significantly higher titer of IgM and IgG in the case of KLH. In conclusion, LTP significantly reinforced humoral immunity by IgM after tongue injection. Vaccination to the tongue can be a novel strategy to acquire immediate immunity.