Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Stem Cell Biology and Regenerative Medicine Research Group, Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
J Control Release. 2023 Aug;360:316-334. doi: 10.1016/j.jconrel.2023.06.025. Epub 2023 Jul 5.
mRNA-lipid nanoparticle (mRNA-LNP) vaccines have proved their efficacy, versatility and unprecedented manufacturing speed during the COVID-19 pandemic. Here we report on the physicochemical properties, thermostability, immunogenicity, and protective efficacy of the nucleoside-modified mRNA-LNP vaccine candidate Iribovax® (also called SNEG2c). Injection of BALB/c mice, rabbits and nonhuman primates with two doses of SNEG2c induced production of high-titers of SARS-CoV-2 spike-specific and receptor-binding domain (RBD)-neutralizing antibodies in immunized animals. In addition to the strong humoral response, SNEG2c elicited substantial Th1-biased T-cell response. Sera from rhesus macaques immunized with a low dose of the vaccine showed robust spike-specific antibody titers 3-24× as high as those in convalescent sera from a panel of COVID-19 patients and 50% virus neutralization geometric mean titer of 1024 against SARS-CoV-2. Strikingly, immunization with SNEG2c completely cleared infectious SARS-CoV-2 from the upper and lower respiratory tracts of challenged macaques and protected them from viral-induced lung and trachea lesions. In contrast, the non-vaccinated macaques developed moderate to severe pulmonary pathology after the viral challenge. We present the results of repeat-dose and local tolerance toxicity and thermostability studies showing how the physicochemical properties of the mRNA-LNPs change over time and demonstrating that SNEG2 is safe, well tolerated and stable for long-term. These results support the planned human trials of SNEG2c.
信使核糖核酸（mRNA）-脂质纳米颗粒（mRNA-LNP）疫苗在 COVID-19 大流行期间已证明其疗效、多功能性和前所未有的制造速度。在这里，我们报告了核苷修饰的 mRNA-LNP 疫苗候选物 Iribovax®（也称为 SNEG2c）的理化性质、热稳定性、免疫原性和保护效力。给 BALB/c 小鼠、兔子和非人类灵长类动物注射两剂 SNEG2c 后，免疫动物体内产生了高滴度的 SARS-CoV-2 刺突特异性和受体结合域（RBD）中和抗体。除了强烈的体液反应外，SNEG2c 还引发了大量 Th1 偏向的 T 细胞反应。用低剂量疫苗免疫的恒河猴血清显示出强大的刺突特异性抗体滴度，比一组 COVID-19 患者恢复期血清中的抗体滴度高 3-24 倍，对 SARS-CoV-2 的 50%病毒中和几何平均滴度为 1024。引人注目的是，SNEG2c 完全清除了受挑战的猕猴上呼吸道和下呼吸道中的传染性 SARS-CoV-2，并保护它们免受病毒引起的肺部和气管损伤。相比之下，未接种疫苗的猕猴在病毒攻击后出现中度至重度肺部病理学。我们介绍了重复剂量和局部耐受毒性以及热稳定性研究的结果，这些结果显示了 mRNA-LNPs 的理化性质随时间的变化，并证明了 SNEG2 是安全的、耐受良好的，并且可以长期稳定。这些结果支持 SNEG2c 的计划人类试验。
