The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and has spread worldwide, with millions of cases and more than 1 million deaths to date. The gravity of the situation mandates accelerated efforts to identify safe and effective vaccines. Here, we generated measles virus (MeV)-based vaccine candidates expressing the SARS-CoV-2 spike glycoprotein (S). Insertion of the full-length S protein gene in two different MeV genomic positions resulted in modulated S protein expression. The variant with lower S protein expression levels was genetically stable and induced high levels of effective Th1-biased antibody and T cell responses in mice after two immunizations. In addition to neutralizing IgG antibody responses in a protective range, multifunctional CD8⁺ and CD4⁺ T cell responses with S protein-specific killing activity were detected. Upon challenge using a mouse-adapted SARS-CoV-2, virus loads in vaccinated mice were significantly lower, while vaccinated Syrian hamsters revealed protection in a harsh challenge setup using an early-passage human patient isolate. These results are highly encouraging and support further development of MeV-based COVID-19 vaccines.

COVID-19 大流行是由严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 引起的，并已在全球蔓延，迄今已有数百万病例和超过 100 万人死亡。形势的严重性要求我们加快努力寻找安全有效的疫苗。在这里，我们生成了表达 SARS-CoV-2 刺突糖蛋白 (S) 的基于麻疹病毒 (MeV) 的候选疫苗。在两个不同的 MeV 基因组位置插入全长 S 蛋白基因导致调节的 S 蛋白表达。具有较低 S 蛋白表达水平的变体具有遗传稳定性，并在两次免疫后在小鼠中诱导高水平的有效 Th1 偏向抗体和 T 细胞反应。除了在保护范围内中和 IgG 抗体反应外，多功能 CD8 ⁺和 CD4⁺检测到具有 S 蛋白特异性杀伤活性的 T 细胞反应。在使用适应小鼠的 SARS-CoV-2 进行攻击后，接种疫苗的小鼠体内的病毒载量显着降低，而接种疫苗的叙利亚仓鼠在使用早期传代人类患者隔离物的严酷挑战设置中显示出保护作用。这些结果非常令人鼓舞，并支持进一步开发基于 MeV 的 COVID-19 疫苗。