InvivoGen社 COVID-19 combination mAb therapy against variants
Here we would like to share a publication from Washington University School of Medicine. The group led by Michael S. Diamond tested the investigational therapeutic antibodies and FDA emergency use approved antibodies, such as LY-CoV555 and LY-CoV016 from Eli Lilly and REGN10933 and REGN10987 from Regeneron, against a panel of SARS-CoV-2 variants of concerns that first emerged in U.K., South Africa, Brazil, India, New York, and California etc.
Take Home Messages
1. In vitro neutralization assay
The team carried out neutralization assays on Vero-TMPRSS2 cells. They found that dual antibodies are effective in neutralizing several variants, even though one of the two antibodies has lost some or all neutralizing ability, e.g. REGN10933 showed reduced ability to neutralize variants with E484 mutations (Indian B.1.617.1), but a combination of REGN10933/REGN10987 remains the potency.
2. Prophylactic efficacy against variants
The researchers injected single or combined antibodies into mice and hamsters. They found that the dual antibodies (REGN10933/REGN10987) can prevent infection of multiple SARS-CoV-2 mutant strains even at low doses, and significantly reduce pro-inflammatory cytokines without emergence of resistance.
3. Therapeutic efficacy against variants
Dual antibodies such as REGN10933/REGN10987 effectively reduced the viral RNA level in mice infected with South Africa B.1.351.
Notably, the FDA revoked the emergency used approval for LY-CoV555 alone to treat COVID-19 recently. In the study, LY-CoV555 was also shown to be least effective against SARS-CoV-2 variants, for example, it was resistant to the Indian B.1.617.1 variant; nevertheless, LY-CoV555/LY-CoV016 antibody therapy was effective to variant carrying N501Y/D614G substitution.
While the effectiveness of single antibody therapy against SARS-CoV-2 variants of concern has diminished, InvivoGen provides pairs of REGN and LY-CoV2 derived antibodies:
InvivoGen also provides A549 human lung carcinoma cells overexpressing ACE2/TMPRSS2, which is more biologically related to COVID-19 than Vero cells:
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