Abstract
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 Statement
All authors are employees and stockholders of Icosavax, Inc.
Abbreviations
- COVID-19
- coronavirus disease 2019
- SARS-CoV-2
- severe acute respiratory syndrome coronavirus 2
- VOCs
- variants of concern
- S
- spike protein
- RBD
- receptor binding domain
- ACE2
- angiotensin-converting enzyme 2
- VLPs
- virus-like particles
- LLPCs
- long-lived plasma cells
- IM
- intramuscular
- SEC
- size exclusion chromatography
- DLS
- dynamic light scattering
- BLI
- biolayer interferometry
- nsTEM
- negative stain transmission electron microscopy
- PNA
- pseudo-particle neutralization assay