HUMAN MONOCLONAL ANTIBODY ENDOWED WITH ANTI-HSV-1 AND -2 ACTIVITY STRONGLY INHIBITS VIRUS REPLICATION

BACKGROUND: Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) are ubiquitous human pathogens, infecting more than 500 million people worldwide. HSV-1 generally infects oral cavity, while HSV-2 the anogenital area. Both viruses undergo latency in the nervous system and are subjected to reactivation under different distress stimuli. HSV infection irresponsive to “classical” current antiviral therapy can be particularly severe among immunocompromised patients and new-borns, causing severe disseminated diseases characterized by high morbidity and mortality. Moreover, the antivirals currently used can be burdened by high toxicity not always allowing their use in therapy. New drugs effective against HSV isolates resistant to standard therapy are therefore clearly needed. METHODS: Human monoclonal antibodies (HuMabs) cross-reactive to both HSV-1 and 2 have been generated from a patient whose serum was able to recognise and neutralise both HSV-1 and -2 reference isolates. HuMabs have been characterised for their binding, neutralising activity and for their capability to inhibit virus replication after adsorption. RESULTS: A new human monoclonal antibody able to recognise both HSV- 1 and -2 has been isolated. The antibody has been then characterised in different antibody formats (Fab and IgG). Both formats have been able to strongly inhibit HSV replication of reference isolates as well as clinical isolates featuring different susceptibility to first-line antiviral drug Acyclovir. CONCLUSIONS: The capability of our antibody to strongly inhibit HSV infection in vitro is the result of both its neutralising activity and its ability to inhibit HSV replication also after virus adsorption. These findings pave the way to the study of our antibody therapeutic activity in vivo.