Journal Article

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

Shi, Wei, Corbett, Kizzmekia S., Zhang, Baoshan, Ou, Li, Werner, Anne, Liu, Tracy, Nguyen, Richard, Yang, Yongping, Phung, Emily, Kwong, Peter D., Graham, Barney S., Wang, Lingshu, Tsybovsky, Yaroslav, Nazzari, Alexandra, Mascola, John R., Olia, Adam S., Abiona, Olubukola M., Wang, Shuishu, Stephens, Tyler, Chuang, Gwo-Yu, Bylund, Tatsiana, Yap, Christina, Zhou, Tongqing, Verardi, Raffaello, Ambrozak, David

2021

Overview

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 ID50 = 386) two weeks after prime immunization, significantly higher than those elicited by a molar equivalent amount of soluble S2P (geometric mean ID50 = 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.

• Publisher: MDPI AG,MDPI
• Subject: Adenoviruses / Antibodies / Antigenicity / Antigens / Cell culture / Clinical trials / Conformation / Coronaviruses / COVID-19 / COVID-19 vaccines / Deoxyribonucleic acid / DNA / Electron microscopy / Enzyme-linked immunosorbent assay / Glycoproteins / Immunization / Immunoassays / Mimicry / Nanoparticles / Neutralization / Neutralizing / neutralizing antibody / Newcastle disease / Newcastle disease virus / Pandemics / Peptides / prefusion-stabilized spike / Proteins / Respiratory syncytial virus / S-2P stabilization / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Spikes / vaccine / Vaccines / Viral diseases / Virus-like particles / Viruses