An engineered bispecific human monoclonal antibody against SARS-CoV-2.
Nat Immunol
; 23(3): 423-430, 2022 03.
Article
in English
| MEDLINE | ID: covidwho-1713201
ABSTRACT
The global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires effective therapies against coronavirus disease 2019 (COVID-19), and neutralizing antibodies are a promising therapy. A noncompeting pair of human neutralizing antibodies (B38 and H4) blocking SARS-CoV-2 binding to its receptor, ACE2, have been described previously. Here, we develop bsAb15, a bispecific monoclonal antibody (bsAb) based on B38 and H4. bsAb15 has greater neutralizing efficiency than these parental antibodies, results in less selective pressure and retains neutralizing ability to most SARS-CoV-2 variants of concern (with more potent neutralizing activity against the Delta variant). We also selected for escape mutants of the two parental mAbs, a mAb cocktail and bsAb15, demonstrating that bsAb15 can efficiently neutralize all single-mAb escape mutants. Furthermore, prophylactic and therapeutic application of bsAb15 reduced the viral titer in infected nonhuman primates and human ACE2 transgenic mice. Therefore, this bsAb is a feasible and effective strategy to treat and prevent severe COVID-19.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibodies, Bispecific
/
SARS-CoV-2
/
Antibodies, Monoclonal
/
Antibodies, Viral
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Nat Immunol
Journal subject:
Allergy and Immunology
Year:
2022
Document Type:
Article
Affiliation country:
S41590-022-01138-w
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