A bioengineered pseudovirus nanoparticle displaying SARS‐CoV 2 RBD fully protects mice from mortality and weight loss caused by SARS‐CoV 2 challenge

Abstract

AbstractThe COVID‐19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused considerable morbidity and mortality worldwide. Although authorized COVID‐19 vaccines have been shown highly effective, their significantly lower efficacy against heterologous variants, and the rapid decrease of vaccine‐elicited immunity raises serious concerns, calling for improved vaccine tactics. To this end, a pseudovirus nanoparticle (PVNP) displaying the receptor binding domains (RBDs) of SARS‐CoV‐2 spike, named S‐RBD, was generated and shown it as a promising COVID‐19 vaccine candidate. The S‐RBD PVNP was produced using both prokaryotic and eukaryotic systems. A 3D structural model of the S‐RBD PVNPs was built based on the known structures of the S60 particle and RBDs, revealing an S60 particle‐based icosahedral symmetry with multiple surface‐displayed RBDs that retain authentic conformations and receptor‐binding functions. The PVNP is highly immunogenic, eliciting high titers of RBD‐specific IgG and neutralizing antibodies in mice. The S‐RBD PVNP demonstrated exceptional protective efficacy, and fully (100%) protected K18‐hACE2 mice from mortality and weight loss after a lethal SARS‐CoV‐2 challenge, supporting the S‐RBD PVNPs as a potent COVID‐19 vaccine candidate. By contrast, a PVNP displaying the N‐terminal domain (NTD) of SARS‐CoV‐2 spike exhibited only 50% protective efficacy. Since the RBD antigens of our PVNP vaccine are adjustable as needed to address the emergence of future variants, and various S‐RBD PVNPs can be combined as a cocktail vaccine for broad efficacy, these non‐replicating PVNPs offer a flexible platform for a safe, effective COVID‐19 vaccine with minimal manufacturing cost and time.