RT Journal Article
SR Electronic
T1 Virus-like particle displaying SARS-CoV-2 receptor binding domain elicits neutralizing antibodies and is protective in a challenge model
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.11.29.518404
DO 10.1101/2022.11.29.518404
A1 McKechnie, Julia L.
A1 Fiala, Brooke
A1 Wolf, Clancey
A1 Ellis, Daniel
A1 Holtzman, Douglas
A1 Feldhaus, Andrew
YR 2022
UL http://biorxiv.org/content/early/2022/11/29/2022.11.29.518404.abstract
AB While the effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has largely been successful, particularly in the developed world, the rise of new variants as well as waning immunity illustrate the need for a new generation of vaccines that provide broader and/or more durable protection against infection and severe disease. Here we describe the generation and characterization of IVX-411, a computationally designed, two-component virus-like particle (VLP) displaying the ancestral SARS-CoV-2 receptor binding domain (RBD) on its surface. Immunization of mice with IVX-411 generates neutralizing antibodies against the ancestral strain as well as three variants of concern. Neutralizing antibody titers elicited by IVX-411 are durable and significantly higher than those elicited by immunization with soluble RBD and spike antigens. Furthermore, immunization with IVX-411 is shown to be protective in a Syrian Golden hamster challenge model using two different strains of SARS-CoV-2. Overall, these studies demonstrate that IVX-411 is highly immunogenic and capable of eliciting broad, protective immunity.Competing Interest StatementAll authors are employees and stockholders of Icosavax, Inc.COVID-19coronavirus disease 2019SARS-CoV-2severe acute respiratory syndrome coronavirus 2VOCsvariants of concernSspike proteinRBDreceptor binding domainACE2angiotensin-converting enzyme 2VLPsvirus-like particlesLLPCslong-lived plasma cellsIMintramuscularSECsize exclusion chromatographyDLSdynamic light scatteringBLIbiolayer interferometrynsTEMnegative stain transmission electron microscopyPNApseudo-particle neutralization assay