HerpHu-mAb - Effective therapeutic antibody against Herpes Simplex Virus Infections
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1 HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections Prof. Dr. Michael Roggendorf Institute of Virology University Duisburg-Essen Germany
2 HV-1 / HV-2: associated diseases Keratitis, Retinitis (Eye) Herpes simplex encephalitis (Brain) Herpes labialis (HV-1) Disseminated Herpes (Lung, Liver) Eczema Herpes (kin) Herpes genitalis (HV-2) transka R, J Clin Virol Morfin F, J Clin Virol Doerr, 2010 Folie Medizinische 2 Virologie Epidemiology: Worldwide, 90% of people are seropositive for one or both virus types. Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 2
3 HV-1 / HV-2: therapy and resistance Antivirals: Aciclovir Foscarnet Cidofovir Nucleoside analogue Pyrophosphate analogue Nucleoside analogue Drug resistance: % normal population 4 7% AID/HIV-patients, chemotherapy recipients, eye infections 14 27% patients after stem cell transplantation Multiresistant strains (ACV, PFA, CDV) Alternatives:? Monoclonal antibody HerpHu-mAb Humanized HV-1/2 gb-targeting antibody Folie 3 transka R, J Clin Virol. 2005; Morfin F, J Clin Virol Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 3
4 HerpHu-mAb human Anti-HV-Ab HerpHu-mAb HerpHu-mAb: Inhibition of the cell-to-cell spread Phase contrast HV-1 Anti-human-Fc No comparable antibody generated in humans (or not isolated so far)! Folie 4 Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 4
5 HV: Disseminated and severe diseases Herpes implex Genitalis 1 : Epidemiology: estimated incidences in U and Europe range from 5 to 24 per 100 people per year Herpes implex Encephalitis 2 : Epidemiology: approx. 1 per 250,000 to 500,000 individuals per year Mortality: untreated about 70%, with Acyclovir about 28% Morbidity: 62% of survivors having some form of neurologic debility only 2.5% return to normal neurologic function Ocular HV diseases: Keratitis 3 and Retinitis: Epidemiology: estimated number of new cases of severe monocular visual impairment or blindness each year, global incidence of HV-induced ocular disease is roughly 1.5 million 1 Malkin JE, Herpes James H, Antiviral Res Folie 3 Farooq, 5 AV; hukla, D, urvey of ophthalmology 2012 Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 5
6 Immunsuppression: Disseminated disease Herpes simplex encephalitis (Brain) Disseminated Herpes (Lung, Liver) Herpes genitalis (HV-1/2) Folie 6 Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 6
7 Immunosuppression: Generalized HV (lethal) Model: NOD/CID mice Infection: vaginal, 1 x 10 6 TCID 50 Virus: HV-1 R10.2 (resistance: ACV, PFA, CDV) ACV: HerpHu-mAb: 50 mg/kg body weight; each 12h 24h, 40h und 56h post infection (300 µg/kg bw i.v.) Folie 7 1 Krawczyk et. al., PNA Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 7
8 Ocular HV diseases: Keratitis Keratitis (Eye) Folie 8 Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 8
![retinal necrosis [%] 100 80 60 p=0.](/docs-images/81/84736524/images/9-4.jpg "09 p=0.")
9 Ocular HV diseases: Retinitis Retinitis (Eye) Mice with acute retinal necrosis [%] p=0.09 p= ** *** *** *** *** PB ACV P PEP T Topical P PEP Controls mab 2c mab hu2c Folie 9 Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 9
10 ummary Antiviral efficacy of HerpHu-mAb towards HV-1/2 ( including drug resistant clinical isolates) was demonstrated in cell culture and animal models Protection of highly immunodeficient NOD/CID mice from generalized, lethal infections Highly effective prevention of HV-mediated Keratitis and Retinitis Promising compound to fight severe and/or drug resistant HV infections Patent applications filed in U, Europe, Canada, China, Japan, India and Brasilia Market volume (estimated): > 500 mio U-$/year Folie 10 Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 10
11 Perspectives und future projects 1.PhaseI clinical trials 2.Charaterization of the B Cell epitope of this HerpHu-mAb 3.Development of a HV1/2 Vaccine containing the relevant B Cell epitopes Universitätsklinikum Bonn Institut für Virologie Anna-Maria Eis-Hübinger Eduard chneweis + Universitätsklinikum Essen Institut für Virologie Adalbert Krawczyk Michael Roggendorf University College London Department of Biochemistry and Molecular Biology Andrew C.R. Martin Universität Tübingen Abteilung für Immunologie Ludger Große-Hovest Nationales Centrum für Tumorerkrankungen Heidelberg Michaela Arndt Jürgen Krauss University of Pennsylvania Department of Microbiology Florent Bender, Ph. D Folie 11 Prof. Dr. Michael Roggendorf HerpHu-mAb - Effective therapeutic antibody against Herpes implex Virus Infections 11
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