PT  - JOURNAL ARTICLE
AU  - McKechnie, Julia L.
AU  - Fiala, Brooke
AU  - Wolf, Clancey
AU  - Ellis, Daniel
AU  - Holtzman, Douglas
AU  - Feldhaus, Andrew
TI  - Virus-like particle displaying SARS-CoV-2 receptor binding domain elicits neutralizing antibodies and is protective in a challenge model
AID  - 10.1101/2022.11.29.518404
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.11.29.518404
4099  - http://biorxiv.org/content/early/2022/11/29/2022.11.29.518404.short
4100  - http://biorxiv.org/content/early/2022/11/29/2022.11.29.518404.full
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