Designed mosaic nanoparticles enhance cross-reactive immune responses in mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39855201.
- Also identified by DOI 10.1016/j.cell.2024.12.015 and PMC identifier 11845252.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Nanoparticle vaccines displaying combinations of SARS-like betacoronavirus (sarbecovirus) receptor-binding domains (RBDs) could protect against SARS-CoV-2 variants and spillover of zoonotic sarbecoviruses into humans. Using a computational approach, we designed variants of SARS-CoV-2 RBDs and selected 7 natural sarbecovirus RBDs, each predicted to fold properly and abrogate antibody responses to variable epitopes. RBDs were attached to 60-mer nanoparticles to make immunogens displaying two (mosaic-2<sub>COM</sub>s), five (mosaic-5<sub>COM</sub>), or seven (mosaic-7<sub>COM</sub>) different RBDs for comparisons with mosaic-8b, which elicited cross-reactive antibodies and protected animals from sarbecovirus challenges. Naive and COVID-19 pre-vaccinated mice immunized with mosaic-7<sub>COM</sub> elicited antibodies targeting conserved RBD epitopes, and their sera exhibited higher binding and neutralization titers against sarbecoviruses than mosaic-8b. Mosaic-2<sub>COM</sub>s and mosaic-5<sub>COM</sub> elicited higher antibody potencies against some SARS-CoV-2 variants than mosaic-7<sub>COM</sub>. However, mosaic-7<sub>COM</sub> elicited more potent responses against zoonotic sarbecoviruses and highly mutated Omicrons, supporting its use to protect against SARS-CoV-2 variants and zoonotic sarbecoviruses.
Medical subject headings
- Nanoparticles
- SARS-CoV-2
- COVID-19
- Spike Glycoprotein, Coronavirus
- COVID-19 Vaccines