Newcastle Disease Virus-Like Particles Displaying Prefusion-Stabilized SARS-CoV-2 Spikes Elicit Potent Neutralizing Responses

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.

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(50) = 386) two weeks after prime immunization, significantly higher than those elicited by a molar equivalent amount of soluble S2P (geometric mean ID(50) = 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.