Messenger RNA (mRNA) vaccines were pivotal in reducing severe acute respiratory syndrome 2 (SARS-CoV-2) infection burden, yet they have not demonstrated robust durability, especially in older adults. Here, we describe a molecular adjuvant comprising a lipid nanoparticle (LNP)–encapsulated mRNA encoding interleukin-12p70 (IL-12p70). The bioactive adjuvant was engineered with a multiorgan protection (MOP) sequence to restrict transcript expression to the intramuscular injection site. Admixing IL-12–MOP (CTX-1796) with the BNT162b2 SARS-CoV-2 vaccine increased spike protein–specific immune responses in mice. Specifically, the benefits of IL-12–MOP adjuvantation included amplified humoral and cellular immunity and increased immune durability for 1 year after vaccination in mice. An additional benefit included the restoration of immunity in aged mice to amounts comparable to those achieved in young adult animals, alongside amplification with a single immunization. Associated enhanced dendritic cell and germinal center responses were observed. Together, these data demonstrate that an LNP-encapsulated IL-12–MOP mRNA-encoded adjuvant can amplify immunogenicity independent of age, demonstrating translational potential to benefit vulnerable populations.

中文翻译：

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通过编码 IL-12p70 mRNA 的受控组织特异性表达来辅助 SARS-CoV-2 mRNA 疫苗


信使 RNA (mRNA) 疫苗对于减少严重急性呼吸综合征 2 (SARS-CoV-2) 感染负担至关重要，但它们尚未表现出强大的耐用性，特别是对于老年人。在这里，我们描述了一种分子佐剂，包含脂质纳米颗粒 (LNP) 封装的编码白细胞介素 12p70 (IL-12p70) 的 mRNA。生物活性佐剂采用多器官保护（MOP）序列进行设计，以将转录物表达限制在肌内注射部位。将 IL-12–MOP (CTX-1796) 与 BNT162b2 SARS-CoV-2 疫苗混合可增加小鼠的刺突蛋白特异性免疫反应。具体来说，IL-12-MOP 佐剂的好处包括增强小鼠的体液和细胞免疫能力，并提高小鼠接种疫苗后 1 年内的免疫持久性。另一个好处包括使老年小鼠的免疫力恢复到与年轻成年动物相当的水平，同时通过单次免疫增强免疫力。观察到相关增强的树突细胞和生发中心反应。总之，这些数据表明，LNP 封装的 IL-12–MOP mRNA 编码佐剂可以增强免疫原性，与年龄无关，证明了使弱势群体受益的转化潜力。