Department of Microbiology and Immunology, Children's Research Institute, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
California National Primate Research Center, University of California at Davis, Davis, CA 95616, USA.
Sci Transl Med. 2023 Mar;15(685):eadd6383. doi: 10.1126/scitranslmed.add6383. Epub 2023 Mar 1.
The U.S. Food and Drug Administration only gave emergency use authorization of the BNT162b2 and mRNA-1273 SARS-CoV-2 vaccines for infants 6 months and older in June 2022. Yet questions regarding the durability of vaccine efficacy, especially against emerging variants, in this age group remain. We demonstrated previously that a two-dose regimen of stabilized prefusion Washington SARS-CoV-2 S-2P spike (S) protein encoded by mRNA encapsulated in lipid nanoparticles (mRNA-LNP) or purified S-2P mixed with 3M-052, a synthetic Toll-like receptor (TLR) 7/8 agonist, in a squalene emulsion (Protein+3M-052-SE) was safe and immunogenic in infant rhesus macaques. Here, we demonstrate that broadly neutralizing and spike-binding antibodies against variants of concern (VOCs), as well as T cell responses, persisted for 12 months. At 1 year, corresponding to human toddler age, we challenged vaccinated rhesus macaques and age-matched nonvaccinated controls intranasally and intratracheally with a high dose of heterologous SARS-CoV-2 B.1.617.2 (Delta). Seven of eight control rhesus macaques exhibited severe interstitial pneumonia and high virus replication in the upper and lower respiratory tract. In contrast, vaccinated rhesus macaques had faster viral clearance with mild to no pneumonia. Neutralizing and binding antibody responses to the B.1.617.2 variant at the day of challenge correlated with lung pathology and reduced virus replication. Overall, the Protein+3M-052-SE vaccine provided superior protection to the mRNA-LNP vaccine, emphasizing opportunities for optimization of current vaccine platforms. The observed efficacy of both vaccines 1 year after vaccination supports the implementation of an early-life SARS-CoV-2 vaccine.
美国食品和药物管理局于 2022 年 6 月仅批准 BNT162b2 和 mRNA-1273 SARS-CoV-2 疫苗用于 6 个月及以上的婴儿进行紧急使用授权。然而，关于该年龄段疫苗效力的持久性，特别是针对新兴变体，仍存在一些问题。我们之前已经证明，两剂由 mRNA 编码的稳定预融合华盛顿 SARS-CoV-2 S-2P 刺突（S）蛋白的配方，该 mRNA 被包裹在脂质纳米颗粒（mRNA-LNP）中，或与 3M-052 混合的 S-2P，一种合成的 Toll 样受体（TLR）7/8 激动剂，在角鲨烯乳剂（Protein+3M-052-SE）中，在婴儿恒河猴中是安全且具有免疫原性的。在这里，我们证明了针对关注变体（VOCs）的广泛中和和刺突结合抗体以及 T 细胞反应可维持 12 个月。在 1 年时，相当于人类幼儿年龄，我们通过鼻腔内和气管内途径用高剂量的异源 SARS-CoV-2 B.1.617.2（Delta）对接种疫苗的恒河猴和年龄匹配的未接种对照进行了挑战。八只对照恒河猴中有七只表现出严重的间质性肺炎和上呼吸道和下呼吸道的高病毒复制。相比之下，接种疫苗的恒河猴具有更快的病毒清除速度，肺炎较轻或没有肺炎。在挑战日时针对 B.1.617.2 变体的中和和结合抗体反应与肺部病理学和减少的病毒复制相关。总体而言，Protein+3M-052-SE 疫苗比 mRNA-LNP 疫苗提供了更好的保护，强调了优化当前疫苗平台的机会。接种疫苗 1 年后两种疫苗的功效表明，早期接种 SARS-CoV-2 疫苗是可行的。
