Extraordinary Titer and Broad Anti-SARS-CoV-2 Neutralization Induced by Stabilized RBD Nanoparticles from Strain BA.5.

Extraordinary Titer and Broad Anti-SARS-CoV-2 Neutralization Induced by Stabilized RBD Nanoparticles from Strain BA.5.

Publication date: Dec 28, 2023

The receptor-binding domain (RBD) of the SARS-CoV-2 spike is a primary target of neutralizing antibodies and a key component of licensed vaccines. Substantial mutations in RBD, however, enable current variants to escape immunogenicity generated by vaccination with the ancestral (WA1) strain. Here, we produce and assess self-assembling nanoparticles displaying RBDs from WA1 and BA. 5 strains by using the SpyTag:SpyCatcher system for coupling. We observed both WA1- and BA. 5-RBD nanoparticles to degrade substantially after a few days at 37 ^0C. Incorporation of nine RBD-stabilizing mutations, however, increased yield ~five-fold and stability such that more than 50% of either the WA1- or BA. 5-RBD nanoparticle was retained after one week at 37 ^0C. Murine immunizations revealed that the stabilized RBD-nanoparticles induced ~100-fold higher autologous neutralization titers than the prefusion-stabilized (S2P) spike at a 2 μg dose. Even at a 25-fold lower dose where S2P-induced neutralization titers were below the detection limit, the stabilized BA. 5-RBD nanoparticle induced homologous titers of 12,795 ID and heterologous titers against WA1 of 1767 ID. Assessment against a panel of β-coronavirus variants revealed both the stabilized BA. 5-RBD nanoparticle and the stabilized WA1-BA. 5-(mosaic)-RBD nanoparticle to elicit much higher neutralization breadth than the stabilized WA1-RBD nanoparticle. The extraordinary titer and high neutralization breadth elicited by stabilized RBD nanoparticles from strain BA. 5 make them strong candidates for next-generation COVID-19 vaccines.

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Concepts Keywords
Nanoparticle COVID-19
Spycatcher encapsulin
Vaccines immunization
nanoparticle vaccine
neutralizing response
RBD
SARS-CoV-2
SpyTag:SpyCatcher conjugation

Semantics

Type Source Name
disease VO titer
disease VO vaccination
disease VO dose
disease MESH COVID-19
drug DRUGBANK (S)-Des-Me-Ampa
disease VO vaccine
disease MESH Allergy
disease MESH Infectious Diseases
disease VO USA
disease IDO host
disease IDO pathogen
disease MESH Malaria
pathway KEGG Malaria
disease VO immunization
disease MESH infection
drug DRUGBANK Coenzyme M
disease VO storage
disease IDO production
drug DRUGBANK Methylergometrine
drug DRUGBANK Phosphate ion
drug DRUGBANK Ampicillin
drug DRUGBANK Isopropyl beta-D-thiogalactopyranoside
disease IDO endotoxin
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Activated charcoal
drug DRUGBANK Copper
drug DRUGBANK Formic Acid
disease VO volume
drug DRUGBANK Tromethamine
drug DRUGBANK Immune Globulin Human
disease IDO assay
drug DRUGBANK Serine
drug DRUGBANK Albendazole
drug DRUGBANK Tretamine
disease VO vaccine antigen
drug DRUGBANK Proline
disease VO immunized
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK L-Threonine
disease VO SKYCovione
disease VO Corbevax
disease VO Abdala
disease VO ZF2001
drug DRUGBANK Amino acids
pathway REACTOME Digestion
disease IDO site
disease VO protocol
disease MESH breakthrough infection
disease VO vaccinated
disease VO efficient
disease VO Pla
drug DRUGBANK Aluminum hydroxide
disease VO vaccine candidate
drug DRUGBANK Guanosine
drug DRUGBANK Mannose
disease MESH weight loss
disease VO effectiveness
disease VO peptide vaccine
disease MESH influenza
drug DRUGBANK Iron
disease VO IroN
disease VO Viruses
drug DRUGBANK Troleandomycin

Original Article

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