Broadly potent anti-SARS-CoV-2 antibody shares 93% of epitope with ACE2 and provides full protection in monkeys.
J Infect
; 87(6): 524-537, 2023 Dec.
Article
in En
| MEDLINE
| ID: mdl-37852477
ABSTRACT
OBJECTIVES:
Due to the rapid evolution of SARS-CoV-2 to variants with reduced sensitivity to vaccine-induced humoral immunity and the near complete loss of protective efficacy of licensed therapeutic monoclonal antibodies, we isolated a potent, broad-spectrum neutralizing antibody that could potentially provide prophylactic protection to immunocompromised patient populations.METHODS:
Spike-specific B-cell clones isolated from a vaccinated post-infected donor were profiled for those producing potent neutralizing antibodies against a panel of SARS-CoV-2 variants. The P4J15 antibody was further characterized to define the structural binding epitope, viral resistance, and in vivo efficacy.RESULTS:
The P4J15 mAb shows <20 ng/ml neutralizing activity against all variants including the latest XBB.2.3 and EG.5.1 sub-lineages. Structural studies of P4J15 in complex with Omicron XBB.1 Spike show that the P4J15 epitope shares â¼93% of its buried surface area with the ACE2 contact region, consistent with an ACE2 mimetic antibody. In vitro selection of SARS-CoV-2 mutants escaping P4J15 neutralization showed reduced infectivity, poor ACE2 binding, and mutations are rare in public sequence databases. Using a SARS-CoV-2 XBB.1.5 monkey challenge model, P4J15-LS confers complete prophylactic protection with an exceptionally long in vivo half-life of 43 days.CONCLUSIONS:
The P4J15 mAb has potential as a broad-spectrum anti-SARS-CoV-2 drug for prophylactic protection of at-risk patient populations.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Angiotensin-Converting Enzyme 2
/
COVID-19
Limits:
Animals
/
Humans
Language:
En
Journal:
J Infect
Year:
2023
Document type:
Article
Affiliation country: