Publication: A Novel Neutralization Antibody Assay Method to Overcome Drug Interference with Better Compatibility with Acid‑Sensitive Neutralizing Antibodies

A group at Merck recently published the above titled article in the AAPS Journal (2023) 25:18
https://doi.org/10.1208/s12248-023-00783-9 (link). They propose a new approach for the isolation and measurement of neutralizing antibodies that minimizes the harsher acid treatments of BEAD assays.  It appears to build on the PandA assay concept. The initial step is the addition of excess drug to form NAb-drug complexes that are precipitated out of the sample for further processing. After a lactic acid dissociation, biotin-bound-drug is added to be in excess of the expected NAb concentration.  The biotin-bound-drug then complexes with the NAb and is captured on the MSD plate along with the non-complexed biotin-bound-drug.  Using a rhuthenium-tagged drug target, the non-complexed biotin-bound-drug is measured. That measure is the inverse of the complexed (non-complexed biotin-bound-drug-Nab) concentration. 

It is interesting in that it may detect acid-labile NAb that may have been destroyed by the use of a BEAD process. The reduction in the use of biotin-bound-drug is also an advantage.

I look forward to seeing how other labs test this approach and provide further insights on its broad applicability.   What do you think about the proposed assay approach?