SARS-CoV-2 monoclonal antibodies with therapeutic potential: Broad neutralizing activity and No evidence of antibody-dependent enhancement.
Antiviral Res
; 195: 105185, 2021 11.
Article
in English
| MEDLINE | ID: covidwho-1458855
ABSTRACT
Monoclonal antibodies (mAbs) are emerging as safe and effective therapeutics against SARS-CoV-2. However, variant strains of SARS-CoV-2 have evolved, with early studies showing that some mAbs may not sustain their efficacy in the face of escape mutants. Also, from the onset of the COVID-19 pandemic, concern has been raised about the potential for Fcγ receptor-mediated antibody-dependent enhancement (ADE) of infection. In this study, plaque reduction neutralization assays demonstrated that mAb 1741-LALA neutralizes SARS-CoV-2 strains B.1.351, D614 and D614G. MAbs S1D2-hIgG1 and S1D2-LALA mutant (STI-1499-LALA) did not neutralize B.1.351, but did neutralize SARS-CoV-2 strains D614 and D614G. LALA mutations did not result in substantial differences in neutralizing abilities between clones S1D2-hIgG1 vs STI-1499-LALA. S1D2-hIgG1, STI-1499-LALA, and convalescent plasma showed minimal ability to induce ADE in human blood monocyte-derived macrophages. Further, no differences in pharmacokinetic clearance of S1D2-hIgG1 vs STI-1499-LALA were observed in mice expressing human FcRn. These findings confirm that SARS-CoV-2 has already escaped some mAbs, and identify a mAb candidate that may neutralize multiple SARS-CoV-2 variants. They also suggest that risk of ADE in macrophages may be low with SARS-CoV-2 D614, and LALA Fc change impacts neither viral neutralization nor Ab clearance.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antibody-Dependent Enhancement
/
SARS-CoV-2
/
Antibodies, Monoclonal
Type of study:
Prognostic study
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
Antiviral Res
Year:
2021
Document Type:
Article
Affiliation country:
J.antiviral.2021.105185
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