NHDL, a recombinant VL/VH hybrid antibody control for IgG2/4 antibodies

• Main Authors: Corinna Lau (Author), Martin Berner McAdam (Author), Grethe Bergseth (Author), Algirdas Grevys (Author), Jack Ansgar Bruun (Author), Judith Krey Ludviksen (Author), Hilde Fure (Author), Terje Espevik (Author), Anders Moen (Author), Jan Terje Andersen (Author), Tom Eirik Mollnes (Author)
• Format: Book
• Published: Taylor & Francis Group, 2020-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1080/19420862.2019.1686319; 1942-0870; 1942-0862
• Keywords: Recombinant antibody; control antibody; IgG2/4; hybrid; therapeutic antibody; Therapeutics. Pharmacology; RM1-950; Immunologic diseases. Allergy; RC581-607
• Source: mAbs, Vol 12, Iss 1 (2020)

The mechanism of action of recombinant IgG2/4 antibodies involves blocking of their target without the induction of effector functions. Examples are eculizumab (Soliris®), which is used clinically to block complement factor C5, as well as anti-human CD14 (r18D11) and anti-porcine CD14 (rMIL2) produced in our laboratory. So far, no proper IgG2/4 control antibody has been available for controlled validation of IgG2/4 antibody functions. Here, we describe the design of a recombinant control antibody (NHDL), which was generated by combining the variable light (VL) and heavy (VH) chains from two unrelated specificities. NHDL was readily expressed and purified as a stable IgG2/4 antibody, and showed no detectable specificity toward any putative antigen present in human or porcine blood. The approach of artificial VL/VH combination may be adopted for the design of other recombinant control antibodies.