A fully human antibody A140 neutralizes abrin toxin via lysosomal intracellular mechanisms, confers potent protection in vitro and in vivo, and reverses transcriptomic dysregulation with a Favorable safety profile.

Abrin is a type II ribosome-inactivating protein extracted from the seeds of Abrus precatorius. Due to its extreme toxicity and ease of acquisition, it is classified as a Category B bioterrorism agent, and no effective antidote is currently available. In this study, a fully human antibody against abrin, designated A140, was generated via screening of a fully human phage-display antibody library and subsequent expression. The A140 antibody demonstrates high affinity while maintaining specificity for its target antigen. It exhibited potent neutralizing efficacy against abrin toxin in both in vitro and in vivo assays. Intriguingly, the A140 antibody, which enters cells via clathrin-dependent and macropinocytic pathways and is subsequently trafficked to lysosomes, does not prevent the cellular entry of abrin, suggesting that its intracellular neutralization activity may function within the lysosomal compartment. Molecular docking studies based on AlphaFold 3 (AF3) indicate that A140 primarily recognizes residues Ser14, Arg169, and Asn173 of the alpha chain of abrin-a. Transcriptomic analysis based on Vero E6 cells showed that A140 antibody treatment was able to reverse almost 80% of the transcriptomic changes induced by abrin. Preliminary toxicity analysis shows that a high dose of the A140 antibody has no impact on the heart, liver, spleen, lungs, kidneys, and other major organs in mice. Our findings indicate that the A140 antibody, as a novel fully human antibody, holds promise as a key therapeutic agent for the treatment of abrin intoxication.