SARS-CoV-2 S2P spike ages through distinct states with altered immunogenicity.
J Biol Chem
; 297(4): 101127, 2021 10.
Article
in English
| MEDLINE | ID: covidwho-1373108
ABSTRACT
The SARS-CoV-2 spike is the primary target of virus-neutralizing antibodies and critical to the development of effective vaccines against COVID-19. Here, we demonstrate that the prefusion-stabilized two-proline "S2P" spike-widely employed for laboratory work and clinical studies-unfolds when stored at 4 °C, physiological pH, as observed by electron microscopy (EM) and differential scanning calorimetry, but that its trimeric, native-like conformation can be reacquired by low pH treatment. When stored for approximately 1 week, this unfolding does not significantly alter antigenic characteristics; however, longer storage diminishes antibody binding, and month-old spike elicits virtually no neutralization in mice despite inducing high ELISA-binding titers. Cryo-EM structures reveal the folded fraction of spike to decrease with aging; however, its structure remains largely similar, although with varying mobility of the receptor-binding domain. Thus, the SARS-CoV-2 spike is susceptible to unfolding, which affects immunogenicity, highlighting the need to monitor its integrity.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
Type of study:
Prognostic study
Topics:
Vaccines
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
J Biol Chem
Year:
2021
Document Type:
Article
Affiliation country:
J.jbc.2021.101127
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