SARS-CoV-2 S2P spike ages through distinct states with altered immunogenicity.
J Biol Chem
; 297(4): 101127, 2021 10.
Article
en En
| MEDLINE
| ID: mdl-34461095
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Glicoproteína de la Espiga del Coronavirus
/
SARS-CoV-2
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Biol Chem
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos