Kling Bio has announced the publication of a peer-reviewed study titled ‘Immune counter-evolution: Immortalized B cell clones can undergo ex vivo directed evolution to counteract viral escape’ in the journal Frontiers in Immunology.
The paper highlights the use of immortalised B-cell libraries to develop therapeutics that adapt to viral evolution and demonstrates how immortalised B-cells can undergo ex vivo directed evolution to generate antibody responses against emerging SARS-CoV-2 escape variants.
The study, conducted solely by Kling Bio, utilised immortalised B-cell libraries derived from human peripheral blood mononuclear cells (PBMCs) and tonsil tissue to identify B-cell clones with cross-reactive neutralisation against SARS-CoV-2 variants. Immortalisation was achieved via retroviral transduction with apoptosis inhibitors, resulting in the libraries retaining full immunoglobulin isotype representation, enabling broad functional screening.
High-throughput screening of 40,000 B-cells per library resulted in the identification of broadly neutralising clones, including monoclonal antibodies with strong, robust activity against the Delta and BA.5 variants. Ex vivo directed evolution further improved potency against emerging immune escape variants such as KP.3 and XEC. The study also reports on a neutralising epitope on Spike-RBD that is fully conserved among all variants reported to date.
In addition, the Kling Bio team engineered a bi-paratopic antibody by combining a broadly neutralising antibody targeting a conserved Spike-RBD epitope with a broadly binding non-neutralising antibody, resulting in enhanced potency against the SARS-CoV-2 variants JN.1 and KP.3.
Stefano Gullà, chief scientific officer at Kling Bio, said: “Our proprietary B-cell platform technologies work together to unlock the full potential of the human immune system to stay ahead of evolving viral threats. By combining high-throughput screening with ex vivo directed evolution, we can rapidly discover and optimize powerful antibodies in days, not months. This breakthrough approach is not just a tool for today’s pandemics; it is a transformative platform for developing next-generation infectious disease therapeutics and redefining how the world responds to future outbreaks.”
The publication follows Kling Bio’s recent announcement of a collaboration and license option agreement with Sanofi. Leveraging Kling Bio’s proprietary primary B-cell immortalisation and screening platform technologies, the collaboration aims to identify neutralising antibodies and respective epitopes against a clinically relevant human viral pathogen.
Jim Cornall is editor of Deeptech Digest and publisher at Ayr Coastal Media. He is an award-winning writer, editor, photographer, broadcaster, designer and author. Contact Jim here.
