AdaptVac Aps, 2970, Hørsholm, Denmark.
Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen and Department of Infectious Disease, Copenhagen University Hospital, 2200, Copenhagen, Denmark.
Nat Commun. 2021 Jan 12;12(1):324. doi: 10.1038/s41467-020-20251-8.
The rapid development of a SARS-CoV-2 vaccine is a global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. RBD antigens are displayed on AP205 CLPs through a split-protein Tag/Catcher, ensuring unidirectional and high-density display of RBD. Both soluble recombinant RBD and RBD displayed on CLPs bind the ACE2 receptor with nanomolar affinity. Mice are vaccinated with soluble RBD or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. The RBD-CLP vaccines induce higher levels of serum anti-spike antibodies than the soluble RBD vaccines. Remarkably, one injection with our lead RBD-CLP vaccine in mice elicits virus neutralization antibody titers comparable to those found in patients that had recovered from COVID-19. Following booster vaccinations, the virus neutralization titers exceed those measured after natural infection, at serum dilutions above 1:10,000. Thus, the RBD-CLP vaccine is a highly promising candidate for preventing COVID-19.
SARS-CoV-2 疫苗的快速开发是全球的当务之急。在这里，我们开发了两种基于衣壳样颗粒（CLP）的疫苗，展示了 SARS-CoV-2 刺突蛋白的受体结合域（RBD）。RBD 抗原通过分裂蛋白 Tag/Catcher 展示在 AP205 CLP 上，确保 RBD 的单向和高密度展示。可溶性重组 RBD 和在 CLP 上展示的 RBD 都以纳摩尔亲和力结合 ACE2 受体。用角鲨烯-水乳液配制的可溶性 RBD 或 CLP 展示的 RBD 对小鼠进行疫苗接种。RBD-CLP 疫苗诱导的血清抗刺突抗体水平高于可溶性 RBD 疫苗。值得注意的是，在小鼠中单次注射我们的 RBD-CLP 疫苗先导物可引发与从 COVID-19 中康复的患者中发现的相当的病毒中和抗体滴度。在加强免疫接种后，病毒中和滴度超过了在血清稀释度超过 1:10000 时自然感染后测量的值。因此，RBD-CLP 疫苗是预防 COVID-19 的极具前景的候选疫苗。
