An Antibody Cocktail Fit for Omicron
The antibody company ImmunoPrecise recently published new data on an antibody cocktail therapy, showing neutralization of the SARS-CoV-2 Delta variant. Their earlier study showed similar efficacy against other variants of concern (VOCs). This well-conceived cocktail is mixed to take down Omicron, and whatever comes next.
This article is posted on our Science Snippets Blog
Antibodies Join the Mix
The virus behind the ongoing global pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has proved itself to be a formidable opponent. Its latest variant, Omicron, has outplayed our vaccines and fueled the largest surge to date. Clearly, COVID-19 is not going away any time soon.
Monoclonal antibodies were the first therapies to receive emergency authorization for treating patients diagnosed with COVID-19 and have demonstrated great potential for preventing severe outcomes. These antibodies target the critical interaction between the cellular receptor angiotensin-converting enzyme 2 (ACE2) and the viral spike protein, specifically at hot spots on the virus receptor-binding domain (RBD).
Efficacy challenges arise when the virus evolves escape mutations. Just this past January, the US Food and Drug Administration (FDA) limited the use of the approved dual-antibody cocktail from Regeneron (casirivimab and imdevimab) and Eli Lilly’s (bamlanivimab and etesevimab), due to diminished potency against the Omicron variant.
Designing for Sustained Efficacy
Antibody cocktails can help to address the problem of neutralization escape by forcing the virus to acquire multiple, often deleterious, mutations. However, the lack of epitope diversity can still leave cocktail regimens vulnerable to mutagenic escape with a single point mutation.
In their latest published study , ImmunoPrecise described a fully human monoclonal antibody cocktail with sustained in vitro and in vivo efficacy against SARS-CoV-2 variants of concern Alpha, Beta and Delta. The cocktail, called TATX-03, contained formulations of four antibodies, each targeting distinct, non-overlapping sights on the spike protein.
Antibodies targeting the spike protein were selected by phage display library panning and then tested for their activity in an in vitro pseudovirus neutralization assay. Extensive epitope binning assays helped identify distinct epitope bins, leading to the antibodies selected for the TATX-03 cocktail. Importantly, viral evolution was factored into the cocktail design to reduce the risk of escape from Omicron or future variants.
Label-Free Epitope Binning
Epitope binning studies using label-free assays on the Octet® Bio-Layer Interferometry (BLI) instrument were integral to the antibody curation process in this study. This technique allows for collecting a range of information about biomolecular interactions, including equilibrium and kinetic rate constants. Running high-throughput antibody-antigen binding assays on a BLI system is also much easier compared to traditional analytical techniques.
Read the paper to learn more about the strategies used to create the TATX-03 cocktail.
If you enjoyed this post, please share it with your friends and colleagues. Be sure to read our previous post exploring the multi-application capabilities of the Octet®️ BLI platform: The Swiss Army Knife of Ligand Binding Assays and our next post Boosting Vaccine Programs Ahead of the Next Pandemic exploring the approach of using high-throughput, label-free technologies for kinetic interaction analysis to quickly select and characterize vaccine candidates.