J08-MUT

An anti-Spike (SARS-CoV-2) antibody.

Phase of research

Potential treatment - pre-clinical evidence

How it helps

Antiviral

Drug status

Experimental

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Supporting references
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Contradictory references
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AI-suggested references
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Clinical trials

General information

J08 is and antibody identified in an antigen-specific memory B cell from a COVID-19 convalescent patient based on affinity toward Spike protein trimer in prefusion conformation and neutralizing capacity against SARS-CoV-2 in Vero E6 cells. The Fc region of the antibody was modified (thus “J08-MUT”), so that Fc receptor binding was abrogated and the serum half-life extended. The modified antibody displayed prophylactic and therapeutic activity against SARS-CoV-2 infection (various strains) in a hamster model in relatively low doses (Andreano et al., 2021).

 


Supporting references

Link Tested on Impact factor Notes Publication date
Extremely potent human monoclonal antibodies from COVID-19 convalescent patients
Spike protein Biophysical assay Animal model In vitro Antibody
in vitro binding assay; in vitro biophysical assay; Vero E6 cells; golden Syrian hamsters; SARS-CoV-2 strains SARS-CoV-2/INMI1-Isolate/2020/Italy,SARS-CoV-2/human/ITA/INMI4/2020 (D614G), and B.1.1.7 38.64

The original antibody was shown to potently bind SARS-CoV-2 Spike protein trimer in prefusion conformation (EC50 of 5.8 ng/mL). The antibody was shown to bind the loop containing residues 477 to 489 of Spike protein. J08-MUT inhibited the interaction between Spike protein and its receptor on Vero E6 cells (IC50 of 78.6 ng/mL). It displayed potent neutralizing capacity against wild type SARS-CoV-2 (IC100 of 3.9 ng/mL) and its variants D614G (IC100 of 7.8 ng/mL) or B.1.1.7. The authors cite (a pre-print) also E484K neutralization. (It did not display SARS-CoV and MERS-CoV pseudotyped virus cross-neutralization.) Intraperitoneal administration of J08-MUT dose-dependently protected hamsters from weight loss (prophylactic dosing) or let the animals regain the lost body weight significantly faster (therapeutic dosing) compared to control. The treatment led to viral RNA elimination in lung tissue at day 3 post infection (at 1 mg/kg in prophylactic and at 4 mg/kg at therapeutic dosing).

Feb/23/2021