AI Article Synopsis

  • - The text discusses a new high-throughput method for discovering broadly-neutralizing monoclonal antibodies, which are crucial for treating infections and animal venom poisoning, using phage display technology and consensus antigens.
  • - The approach was applied to create a consensus sphingomyelinase from venom sources like the recluse spider and Gadim scorpion, involving multiple rounds of selection and screening to find effective antibodies.
  • - The results showed that this method produced two specific antibodies that bind and neutralize toxic activities from venom, proving it to be more effective than traditional methods for yielding cross-neutralizing antibodies.

Article Abstract

Broadly-neutralizing monoclonal antibodies are becoming increasingly important tools for treating infectious diseases and animal envenomings. However, designing and developing broadly-neutralizing antibodies can be cumbersome using traditional low-throughput iterative protein engineering methods. Here, we present a new high-throughput approach for the standardized discovery of broadly-neutralizing monoclonal antibodies relying on phage display technology and consensus antigens representing average sequences of related proteins. We showcase the utility of this approach by applying it to toxic sphingomyelinases from the venoms of species from very distant orders of the animal kingdom, the recluse spider and Gadim scorpion. First, we designed a consensus sphingomyelinase and performed three rounds of phage display selection, followed by DELFIA-based screening and ranking, and benchmarked this to a similar campaign involving cross-panning against recombinant versions of the native toxins. Second, we identified two scFvs that not only bind the consensus toxins, but which can also neutralize sphingomyelinase activity of native whole venom in vitro. Finally, we conclude that the phage display campaign involving the use of the consensus toxin was more successful in yielding cross-neutralizing scFvs than the phage display campaign involving cross-panning.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10868436PMC
http://dx.doi.org/10.1002/pro.4901DOI Listing

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