Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
EBioMedicine. 2021 Jan;63:103197. doi: 10.1016/j.ebiom.2020.103197. Epub 2021 Jan 7.
SARS-CoV-2 has caused a global pandemic, infecting millions of people. A safe, effective vaccine is urgently needed and remains a global health priority. Subunit vaccines are used successfully against other viruses when administered in the presence of an effective adjuvant.
We evaluated three different clinically tested adjuvant systems in combination with the SARS-CoV-2 pre-fusion stabilized (S-2P) spike protein using a one-dose regimen in mice.
Whilst spike protein alone was only weakly immunogenic, the addition of either Aluminum hydroxide, a squalene based oil-in-water emulsion system (SE) or a cationic liposome-based adjuvant significantly enhanced antibody responses against the spike receptor binding domain (RBD). Kinetics of antibody responses differed, with SE providing the most rapid response. Neutralizing antibodies developed after a single immunization in all adjuvanted groups with ID titers ranging from 86-4063. Spike-specific CD4 T helper responses were also elicited, comprising mainly of IFN-γ and IL-17 producing cells in the cationic liposome adjuvanted group, and more IL-5- and IL-10-secreting cells in the AH group.
These results demonstrate that adjuvanted spike protein subunit vaccine is a viable strategy for rapidly eliciting SARS-CoV-2 neutralizing antibodies and CD4 T cell responses of various qualities depending on the adjuvant used, which can be explored in further vaccine development against COVID-19.
This work was supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.
SARS-CoV-2 已造成全球大流行，感染了数百万人。急需安全有效的疫苗，这仍然是全球卫生重点。当与有效的佐剂一起使用时，亚单位疫苗在针对其他病毒时已成功使用。
我们在小鼠中评估了三种不同的临床测试佐剂系统与 SARS-CoV-2 预融合稳定（S-2P）刺突蛋白联合使用时的情况，采用一剂方案。
尽管单独的刺突蛋白仅具有弱免疫原性，但添加氢氧化铝、角鲨烯水包油乳液系统（SE）或阳离子脂质体佐剂可显著增强针对刺突受体结合域（RBD）的抗体反应。抗体反应的动力学不同，SE 提供了最快的反应。在所有佐剂组中，单次免疫后均产生了中和抗体，ID 滴度范围为 86-4063。还引发了针对 Spike 的 CD4 T 辅助反应，在阳离子脂质体佐剂组中主要由 IFN-γ和 IL-17 产生细胞组成，在 AH 组中则由更多的 IL-5 和 IL-10 分泌细胞组成。
这些结果表明，佐剂 Spike 蛋白亚单位疫苗是一种可行的策略，可以快速引起 SARS-CoV-2 中和抗体和 CD4 T 细胞反应，具体取决于所使用的佐剂，这可以在针对 COVID-19 的进一步疫苗开发中进行探索。
这项工作得到了欧盟 Horizon 2020 研究与创新计划的支持，协议号为 101003653。
