IN VIVO PROTECTION CONFERRED BY HUMAN MONOCLONAL ANTIBODY DIRECTED AGAINST HSV-1 AND 2

BACKGROUND: The worldwide incidence of Herpes Simplex Virus (HSV) infections is becoming a significant threat due to the growing number of individuals that are mainly prone to develop severe HSV disease such as CNS involvement. This is the case of patients with an impaired immune system, as post-transplant patients, those infected by HIV or perinatal infected new-borns. In these patients, severe diseases can develop after therapeutic failure of the standard therapy consisting in first line drug Acyclovir (ACV) due to the presence of isolates not fully susceptible to ACV. Moreover the high toxicity of second line drugs often compromises their use in therapy. Finally, the presence of isolates resistant both to first and second line treatments completely abrogate the possibility to contain the infection. Given that, developing new antiviral molecules able to inhibit virus infection certainly represents a medical need. METHODS: A human monoclonal antibody endowed with strong neutralizing activity against HSV-1 and -2 previously characterised in vitro has been tested in C57BL/6 mice for its activity against HSV-1 and HSV-2 infections. More in details, HSV-2 strain MS and HSV-1 strain LV have been used to perform both vaginal and ocular challenges. The antibody has been administered both topically and systemically, and has been tested both for prophylaxis and therapy. RESULTS: The antibody proved to be extremely protective against HSV-1 and HSV-2 infections when administered systemically. Importantly, its antiviral activity has been observed both therapeutically and prophylactically even with a single boost administration of the mAb. CONCLUSION: These experiments showed that the human mAb able to recognise and neutralise both HSV-1 and 2 is able to protect animals challenged with lethal doses of both HSV types opening new perspectives to its possible clinical use.