Heterologous Sarbecovirus Receptor Binding Domains as Scaffolds for SARS-CoV-2 Receptor Binding Motif Presentation.
ACS Infect Dis
; 10(2): 553-561, 2024 02 09.
Article
in En
| MEDLINE
| ID: mdl-38281136
ABSTRACT
Structure-guided rational immunogen design can generate optimized immunogens that elicit a desired humoral response. Design strategies often center on targeting conserved sites on viral glycoproteins that will ultimately confer potent neutralization. For SARS-CoV-2 (SARS-2), the surface-exposed spike glycoprotein includes a broadly conserved portion, the receptor binding motif (RBM), that is required to engage the host cellular receptor, ACE2. Expanding humoral responses to this site may result in a more potent neutralizing antibody response against diverse sarbecoviruses. Here, we used a "resurfacing" approach and iterative design cycles to graft the SARS-2 RBM onto heterologous sarbecovirus scaffolds. The scaffolds were selected to vary the antigenic distance relative to SARS-2 to potentially focus responses to RBM. Multimerized versions of these immunogens elicited broad neutralization against sarbecoviruses in the context of preexisting SARS-2 immunity. These validated engineering approaches can help inform future immunogen design efforts for sarbecoviruses and are generally applicable to other viruses.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Severe acute respiratory syndrome-related coronavirus
/
COVID-19
Limits:
Humans
Language:
En
Journal:
ACS Infect Dis
/
ACS infect. dis
/
ACS infectious diseases
Year:
2024
Document type:
Article
Affiliation country:
United States
Country of publication:
United States