Development of affordable and effective vaccines that can also protect vulnerable populations such as the elderly from COVID-19-related morbidity and mortality is a public health priority. Here we took a systematic and iterative approach by testing several SARS-CoV-2 protein antigens and adjuvants to identify a combination that elicits neutralizing antibodies and protection in young and aged mice. In particular, SARS-CoV-2 receptorbinding domain (RBD) displayed as a protein nanoparticle (RBD-NP) was a highly effective antigen, and when formulated with an oil-in-water emulsion containing Carbohydrate fatty acid MonoSulphate derivative (CMS) induced the highest levels of cross-neutralizing antibodies compared to other oil-in-water emulsions or AS01B. Mechanistically, CMS induced antigen retention in the draining lymph node (dLN) and expression of cytokines, chemokines and type I interferon-stimulated genes at both injection site and dLN. Overall, CMS:RBD-NP is effective across multiple age groups and is an exemplar of a SARS-CoV-2 subunit vaccine tailored to the elderly.

中文翻译：

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含佐剂的 SARS-CoV-2 RBD 纳米颗粒可在老年小鼠中引发中和抗体和完全保护性免疫

开发负担得起的有效疫苗，同时保护老年人等弱势群体免受 COVID-19 相关发病率和死亡率的影响，是公共卫生的优先事项。在这里，我们通过测试几种 SARS-CoV-2 蛋白抗原和佐剂，采取了一种系统和迭代的方法，以确定在年轻和老年小鼠中引发中和抗体和保护的组合。特别是 SARS-CoV-2 受体结合域 (RBD) 显示为蛋白质纳米颗粒 (RBD-NP) 是一种高效抗原，当与含有碳水化合物脂肪酸单硫酸盐衍生物 (CMS) 的水包油乳液配制时与其他水包油乳液或 AS01B 相比，交叉中和抗体水平最高。从机制上讲，CMS 诱导引流淋巴结 (dLN) 中的抗原保留以及细胞因子、趋化因子和 I 型干扰素刺激基因在注射部位和 dLN 中的表达。总体而言，CMS:RBD-NP 对多个年龄组均有效，是为老年人量身定制的 SARS-CoV-2 亚单位疫苗的典范。