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DOI: 10.1055/s-0038-1671386
Herpevizumab, a potent humanized antibody to treat anogenital herpes simplex virus (HSV-1/2) infection – Summary of preclinical data and perspectives of an ongoing clinical trial
Publikationsverlauf
Publikationsdatum:
20. September 2018 (online)
There are two types of human herpes simplex virus, HSV-1 and HSV-2. Both can cause infections of the lip, mouth, face, throat and cornea of the eye as well as anogenital infections. Primary infection with HSV at mucosal sites can remain asymptomatic or be associated with local pain, blisters or other symptoms. Recurrences may become chronic, resulting in physical disabilities, social exclusion, and psychological distress over time. In addition, severe and life-threatening infections can occur in newborns and in immunocompromised individuals. Chemotherapeutics such as aciclovir (ACV) targeting viral DNA replication have been applied as anti-HSV drugs, however, viral resistance presents a major limitation.
We have developed Herpevizumab (HDIT101), a potent humanized antibody with a unique mechanism of action. HDIT101 targets a common epitope on HSV-1/2 glycoprotein B (gB), an envelope protein that is essential for infection. HDIT101 potently neutralizes cell-free circulating HSV particles but also effectively inhibits cell-to-cell spread, a key process by which HSV evades immune clearance. Due to its dual mode of action using a completely different mechanism to currently applied antiviral drugs, HDIT101 is an ideal candidate for clinical application, especially for the treatment of common drug-resistant HSV infections. Here we summarize our current knowledge and preclinical results and give insight into an ongoing randomized, double-blinded, placebo-controlled first-in-man (FIM) phase 1a trial as well as perspectives for a planned clinical phase 1b/2 study to treat anogenital HSV infections. The development of potent alternative treatment strategies as demonstrated by HDIT101, will help overcoming HSV-associated morbidities and life-threating diseases.