Multimechanistic Monoclonal Antibodies (MAbs) Targeting Staphylococcus aureus Alpha-Toxin and Clumping Factor A: Activity and Efficacy Comparisons of a MAb Combination and an Engineered Bispecific Antibody Approach

Tkaczyk C, et al., 61(8). pii: e00629-17, Antimicrob Agents Chemother., 2017

Staphylococcus aureus is a bacterial pathogen that causes a number of infectious diseases including skin infections, bloodstream infections, and respiratory infections. The virulence factors, secreted alpha-toxin, and surface expressed clumping factor A (ClfA) play key roles in S. aureus bloodstream infections. Described herein is the engineering of bispecific antibodies (BiSAbs) with anti-alpha-toxin and anti-ClfA activities by combining multimechanistic MAbs targeting alpha-toxin and ClfA. Furthermore, the activities and efficacies of the engineered BiSAbs were compared with different antibody pairs targeting the same antigens. Anti-ClfA MAbs 11H10 and SAR114 were analyzed in a competition assay for binding to ClfA001 by using Bio-Layer Interferometry (BLI). A Pall ForteBio Octet RED96 instrument equipped with Amino-Propyl-Silane (APS) Biosensor probes were used to perform all BLI assays. APS sensor tips were immobilized with the first MAb (SAR114 or 11H10). Blocking agent, bovine serum albumin (BSA) was used to block any unoccupied Biosensor binding sites. Subsequently, sensor tips were dipped in ClfA001. Biosensor probes were then moved into wells containing the second MAb (SAR114 or 11H10). According to the competition assay results, both MAbs (11H10 and SAR114) bind to an overlapping epitope on ClfA001. Overall results of this investigation suggest that a BiSAb approach is not always superior to a MAb combination approach, and appropriate method selection likely depend on many factors, including antigen location, antigen concentration, and the binding affinities of MAb components.

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