In this episode of Drug Target Review’s podcast, in association with Molecular Devices, Editor Victoria Rees speaks with Dr Carter Mitchell, Chief Science Officer at Kemp Proteins and Dr Sharath Madasu, Manager of Protein Characterisation at Kemp Proteins about the use of monoclonal antibodies (mAbs) against SARS-CoV-2 and why the workflow to develop these biologics has changed over the course of the pandemic.
The speakers began by explaining why mAbs are useful against SARS-CoV-2 and how they work to neutralise the virus.
"In particular with SARS-CoV-2, you want to disrupt the binding of spike proteins with ACE2 receptors and most of the neutralising antibodies used disrupt this interaction. We are essentially denying the entry into the host cells," said Madasu.
Madasu and Mitchell then went on to explore the rates of effectiveness seen with antibodies in relation to SARS-CoV-2. While they agreed that the antibodies given Emergency Use Authorization (EUA) worked well against the wildtype virus and for the first several variants that emerged, they said that mAbs were shown to be less effective at neutralising the Omicron variant.
"With the Omicron variant, there are at least 36 mutations that are found on the spike protein... If these mutations result in differential glycosylation, that allows for the virus to be able to evade previously formed immunological responses or evade the neutralisation of mAbs," explained Mitchell.
However, both Mitchell and Madasu said that mAbs remain an effective tool against SARS-CoV-2. Therefore, developing mAbs that can tackle the Omicron variant is essential and having an accelerated discovery and development workflow is thus key.
"The process for antibody development has been established and the pandemic, I believe, created a sense of urgency to develop these antibodies," said Madasu.
The speakers also discussed how automation is crucial in mAb development, saving researchers time and money.
"Traditionally, we grow hybridomas in semi-solid mediums that allows for single cells to form a colony – but it is a slow process,” said Madasu. “Now, we have tools and robotic instruments that can allow us to print single cells into each well, thereby improving both the throughput as well as the efficiency."
“One of the great ways to decrease turnaround time is to implement robotics,” Mitchell summarised.
Mitchell and Madasu concluded that mAbs will be vital in ending the pandemic, working in tandem with other therapeutics and vaccines. Therefore, making sure that development pipelines for mAbs are as efficient as possible will allow patients to receive their required treatments sooner.
Keep an eye out for Drug Target Review’s next podcast, coming soon!