Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2.

Structural and biochemical rationale for Beta variant protein booster vaccine broad cross-neutralization of SARS-CoV-2.

Publication date: Jan 23, 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the COVID-19 pandemic, uses a surface expressed trimeric spike glycoprotein for cell entry. This trimer is the primary target for neutralizing antibodies making it a key candidate for vaccine development. During the global pandemic circulating variants of concern (VOC) caused several waves of infection, severe disease, and death. The reduced efficacy of the ancestral trimer-based vaccines against emerging VOC led to the need for booster vaccines. Here we present a detailed characterization of the Sanofi Beta trimer, utilizing cryo-EM for structural elucidation. We investigate the conformational dynamics and stabilizing features using orthogonal SPR, SEC, nanoDSF, and HDX-MS techniques to better understand how this antigen elicits superior broad neutralizing antibodies as a variant booster vaccine. This structural analysis confirms the Beta trimer preference for canonical quaternary structure with two RBD in the up position and the reversible equilibrium between the canonical spike and open trimer conformations. Moreover, this report provides a better understanding of structural differences between spike antigens contributing to differential vaccine efficacy.

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Concepts Keywords
Death Antibodies
Global Beta
Glycoprotein Booster
Stabilizing Broad
Vaccine Cov
Neutralizing
Pandemic
Sars
Severe
Spike
Structural
Trimer
Vaccine
Vaccines
Variant

Semantics

Type Source Name
disease VO vaccine
disease VO Severe acute respiratory syndrome coronavirus 2
disease MESH COVID-19 pandemic
disease VO Glycoprotein
disease IDO cell
disease MESH infection
disease MESH death
drug DRUGBANK Tropicamide
disease VO report
disease VO vaccine efficacy
drug DRUGBANK Coenzyme M
disease MESH Emergency
disease VO immunization
disease IDO host
disease VO vaccine candidate
disease VO Canada
disease VO USA
disease VO population
disease VO storage
drug DRUGBANK Proline
drug DRUGBANK Amino acids
disease MESH point mutations
disease MESH SD1
disease VO time
pathway REACTOME Digestion
disease VO efficiency
disease VO vaccination
drug DRUGBANK Hexocyclium
disease IDO process
disease VO efficient
disease VO effectiveness
drug DRUGBANK Trestolone
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Albendazole
drug DRUGBANK Nitrogen
disease VO dose
drug DRUGBANK Sodium hydroxide
disease VO NAP
drug DRUGBANK Phosphate ion
disease VO injection
drug DRUGBANK Pepsin
drug DRUGBANK Flunarizine
disease IDO country
drug DRUGBANK Carboxyamidotriazole
disease IDO infectivity
disease VO Comirnaty
disease MESH pertussis
pathway KEGG Pertussis
drug DRUGBANK Etoperidone
disease VO company

Original Article

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