Adalbert Krawczyk

Generation and characterisation of a humanized monoclonal antibody for prophylaxis and therapy of
Herpes Simplex Virus infections

Herpes Simplex Virus type 1 (HSV-1) and type 2 (HSV-2) are wide spread viruses in adults. After primary lytic infection, HSV establishes a lifelong latent infection. From its state of latency the virus periodically reactivates. Human anti-HSV-antibodies generated after primary infection are essential for establishment of the latent infection, but do not inhibit the directly virus spread from cell-to-cell. Furthermore, in immunocompromized individuals increasing occurrence of Aciclovir- and multiresistant HSV is associated with serve life-threatening infections. We isolated a murine monoclonal antibody, mAb 2c, which proved to be extremely effective in suppression of HSV infections in normal and immunocompromized mice. In this study we demonstrated that antibody valency has a major effect on antiviral efficiency. For clinical treatment we eliminated the immunogenic potential of mAb 2c by a new humanization approach. The humanized antibody hu2c retained the biological properties of the parental murine monoclonal antibody and showed extraordinary neutralization efficiency towards ACV- and multiresistant HSV strains in vitro and in vivo. The data obtained hold great promise to further develop of mAb hu2c as an alternative drug for HSV therapy.

1st supervisor:  Prof. Dr. M. Roggendorf
2nd supervisor:  Dr. M.A.E. Arndt

Institute: Department of Virology, University Hospital Essen, University of Duisburg-Essen

Telephone: +49 (0)201 - 723 - 2721
E-mail: adalbert.krawczyk@uni-due.de