Zhang Lizhou, More Kunal R, Ojha Amrita, Jackson Cody B, Quinlan Brian D, Li Hao, He Wenhui, Farzan Michael, Pardi Norbert, Choe Hyeryun
Division of Infectious Disease, Boston Children's Hospital, Boston, MA, USA.
Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
NPJ Vaccines. 2023 Oct 11;8(1):156. doi: 10.1038/s41541-023-00751-6.
During the COVID-19 pandemic, Pfizer-BioNTech and Moderna successfully developed nucleoside-modified mRNA lipid nanoparticle (LNP) vaccines. SARS-CoV-2 spike protein expressed by those vaccines are identical in amino acid sequence, but several key components are distinct. Here, we compared the effect of ionizable lipids, untranslated regions (UTRs), and nucleotide composition of the two vaccines, focusing on mRNA delivery, antibody generation, and long-term stability. We found that the ionizable lipid, SM-102, in Moderna's vaccine performs better than ALC-0315 in Pfizer-BioNTech's vaccine for intramuscular delivery of mRNA and antibody production in mice and long-term stability at 4 °C. Moreover, Pfizer-BioNTech's 5' UTR and Moderna's 3' UTR outperform their counterparts in their contribution to transgene expression in mice. We further found that varying N1-methylpseudouridine content at the wobble position of mRNA has little effect on vaccine efficacy. These findings may contribute to the further improvement of nucleoside-modified mRNA-LNP vaccines and therapeutics.
在新冠疫情期间，辉瑞- BioNTech和莫德纳成功研发出核苷修饰的信使核糖核酸脂质纳米颗粒（LNP）疫苗。这些疫苗所表达的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白氨基酸序列相同，但几个关键成分有所不同。在此，我们比较了两种疫苗的可电离脂质、非翻译区（UTR）和核苷酸组成的影响，重点关注信使核糖核酸递送、抗体产生和长期稳定性。我们发现，莫德纳疫苗中的可电离脂质SM-102在将信使核糖核酸肌肉注射到小鼠体内、产生抗体以及在4°C下的长期稳定性方面，比辉瑞- BioNTech疫苗中的ALC-0315表现更好。此外，辉瑞- BioNTech的5'UTR和莫德纳的3'UTR在对小鼠转基因表达的贡献方面优于各自的对应部分。我们还发现，信使核糖核酸摆动位置的N1-甲基假尿苷含量变化对疫苗效力影响不大。这些发现可能有助于进一步改进核苷修饰的信使核糖核酸-LNP疫苗和疗法。
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