After over a billion of vaccinations with messenger RNA-lipid nanoparticle (mRNA-LNP) based SARS-CoV-2 vaccines, anaphylaxis and other manifestations of hypersensitivity can be considered as very rare adverse events. Although current recommendations include avoiding a second dose in those with first-dose anaphylaxis, the underlying mechanisms are unknown; therefore, the risk of a future reaction cannot be predicted. Given how important new mRNA constructs will be to address the emergence of new viral variants and viruses, there is an urgent need for clinical approaches that would allow a safe repeated immunization of high-risk individuals and for reliable predictive tools of adverse reactions to mRNA vaccines. In many aspects, anaphylaxis symptoms experienced by the affected vaccine recipients resemble those of infusion reactions to nanomedicines. Here we share lessons learned over a decade of nanomedicine research and discuss the current knowledge about several factors that individually or collectively contribute to infusion reactions to nanomedicines. We aim to use this knowledge to inform the SARS-CoV-2 lipid-nanoparticle-based mRNA vaccine field.

在使用基于信使 RNA-脂质纳米颗粒 (mRNA-LNP) 的 SARS-CoV-2 疫苗接种超过 10 亿次疫苗后，过敏反应和其他超敏反应表现可被视为非常罕见的不良事件。尽管目前的建议包括避免对首次给药过敏反应的患者进行第二次给药，但其潜在机制尚不清楚；因此，无法预测未来反应的风险。鉴于新的 mRNA 结构对于解决新病毒变体和病毒的出现有多么重要，迫切需要临床方法来允许对高风险个体进行安全的重复免疫，以及可靠的 mRNA 疫苗不良反应预测工具. 在许多方面，受影响的疫苗接种者所经历的过敏反应症状类似于对纳米药物的输注反应。在这里，我们分享了十年来纳米医学研究的经验教训，并讨论了当前关于单独或共同导致纳米药物输注反应的几个因素的知识。我们的目标是利用这些知识为基于 SARS-CoV-2 脂质纳米颗粒的 mRNA 疫苗领域提供信息。