Yang Yongping, Shi Wei, Abiona Olubukola M, Nazzari Alexandra, Olia Adam S, Ou Li, Phung Emily, Stephens Tyler, Tsybovsky Yaroslav, Verardi Raffaello, Wang Shuishu, Werner Anne, Yap Christina, Ambrozak David, Bylund Tatsiana, Liu Tracy, Nguyen Richard, Wang Lingshu, Zhang Baoshan, Zhou Tongqing, Chuang Gwo-Yu, Graham Barney S, Mascola John R, Corbett Kizzmekia S, Kwong Peter D
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
Vaccines (Basel). 2021 Jan 21;9(2):73. doi: 10.3390/vaccines9020073.
The COVID-19 pandemic highlights an urgent need for vaccines that confer protection from SARS-CoV-2 infection. One approach to an effective COVID-19 vaccine may be through the display of SARS-CoV-2 spikes on the surface of virus-like particles, in a manner structurally mimicking spikes on a native virus. Here we report the development of Newcastle disease virus-like particles (NDVLPs) displaying the prefusion-stabilized SARS-CoV-2 spike ectodomain (S2P). Immunoassays with SARS-CoV-2-neutralizing antibodies revealed the antigenicity of S2P-NDVLP to be generally similar to that of soluble S2P, and negative-stain electron microscopy showed S2P on the NDVLP surface to be displayed with a morphology corresponding to its prefusion conformation. Mice immunized with S2P-NDVLP showed substantial neutralization titers (geometric mean ID = 386) two weeks after prime immunization, significantly higher than those elicited by a molar equivalent amount of soluble S2P (geometric mean ID = 17). Neutralizing titers at Week 5, two weeks after a boost immunization with S2P-NDVLP doses ranging from 2.0 to 250 μg, extended from 2125 to 4552, and these generally showed a higher ratio of neutralization versus ELISA than observed with soluble S2P. Overall, S2P-NDVLP appears to be a promising COVID-19 vaccine candidate capable of eliciting substantial neutralizing activity.
2019年冠状病毒病（COVID-19）大流行凸显了对能预防严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的疫苗的迫切需求。研发一种有效的COVID-19疫苗的一种方法可能是通过在病毒样颗粒表面展示SARS-CoV-2刺突，其方式在结构上模仿天然病毒上的刺突。在此，我们报告了展示预融合稳定的SARS-CoV-2刺突胞外域（S2P）的新城疫病毒样颗粒（NDVLPs）的研发情况。用SARS-CoV-2中和抗体进行的免疫分析显示，S2P-NDVLP的抗原性与可溶性S2P的抗原性总体相似，负染色电子显微镜显示NDVLP表面的S2P以与其预融合构象相对应的形态展示。用S2P-NDVLP免疫的小鼠在初次免疫两周后显示出较高的中和滴度（几何平均ID50 = 386），显著高于等摩尔量的可溶性S2P所诱导的中和滴度（几何平均ID50 = 17）。在用2.0至250μg的S2P-NDVLP剂量加强免疫两周后的第5周，中和滴度从2125延伸至4552，并且这些中和滴度与酶联免疫吸附测定（ELISA）的比值通常高于可溶性S2P。总体而言，S2P-NDVLP似乎是一种有前景的COVID-19疫苗候选物，能够引发显著的中和活性。
