1. Development of a highly effective combination monoclonal antibody therapy against Herpes simplex virus
- Author
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Narges Seyfizadeh, David Kalbermatter, Thomas Imhof, Moritz Ries, Christian Müller, Leonie Jenner, Elisabeth Blumenschein, Alexandra Yendrzheyevskiy, Frank Grün, Kevin Moog, Daniel Eckert, Ronja Engel, Philipp Diebolder, Mohamed Chami, Jürgen Krauss, Torsten Schaller, and Michaela Arndt
- Subjects
Herpes simplex virus (HSV) ,Glycoprotein B (gB) ,Therapeutic monoclonal antibody ,Combination therapy ,Medicine - Abstract
Abstract Background Infections with Herpes simplex virus (HSV)-1 or -2 usually present as mild chronic recurrent disease, however in rare cases can result in life-threatening conditions with a large spectrum of pathology. Monoclonal antibody therapy has great potential especially to treat infections with virus resistant to standard therapies. HDIT101, a humanized IgG targeting HSV-1/2 gB was previously investigated in phase 2 clinical trials. The aim of this study was to develop a next-generation therapy by combining different antiviral monoclonal antibodies. Methods A lymph-node derived phage display library (LYNDAL) was screened against recombinant gB from Herpes simplex virus (HSV) -1 and HDIT102 scFv was selected for its binding characteristics using bio-layer interferometry. HDIT102 was further developed as fully human IgG and tested alone or in combination with HDIT101, a clinically tested humanized anti-HSV IgG, in vitro and in vivo. T-cell stimulating activities by antigen-presenting cells treated with IgG-HSV immune complexes were analyzed using primary human cells. To determine the epitopes, the cryo-EM structures of HDIT101 or HDIT102 Fab bound to HSV-1F as well as HSV-2G gB protein were solved at resolutions
- Published
- 2024
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