Site-directed neutralizing antibodies targeting structural sites on SARS-CoV-2 spike protein.
N Biotechnol
; 80: 27-36, 2024 May 25.
Article
em En
| MEDLINE
| ID: mdl-38128698
ABSTRACT
'Epivolve' (epitope evolution) is an innovative paratope-evolving technology using a haptenated peptide or protein immunogen as a means of directing the in vivo immune response to specifically targeted sites at a one amino acid residue resolution. Guided by protein structural analysis, Epivolve technology was tested to develop site-directed neutralizing antibodies (nAbs) in a systematic fashion against the SARS-CoV-2 Receptor Binding Domain (RBD). Thirteen solvent-exposed sites covering the ACE2 receptor-binding interface were targeted. Immunogens composed of each targeted site were used to immunize rabbits in separate cohorts. In vivo site-directed immune responses against all 13 targets were demonstrated by B cell secreted IgG and recombinant IgG testing. One site, SL13 (Y505) which mutates from tyrosine to histidine in the SARS-CoV-2 Omicron variant, was chosen as a proof-of-concept (PoC) model for further functional monoclonal antibody development. Epivolve technology demonstrated the capabilities of generating pan-variant antibodies and nAbs against the SARS-CoV-2 primary strain and the Omicron variant.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Neutralizantes
/
COVID-19
Limite:
Animals
/
Humans
Idioma:
En
Revista:
N Biotechnol
/
New biotechnology (Online)
Assunto da revista:
BIOLOGIA MOLECULAR
/
ENGENHARIA BIOMEDICA
Ano de publicação:
2024
Tipo de documento:
Article