Entry inhibition of HSV-1 and -2 protects mice from viral lethal challenge

• Published in: Antiviral research 2017-07, Vol.143, p.48-61
• Main Authors: Clementi, Nicola, Criscuolo, Elena, Cappelletti, Francesca, Quaranta, Paola, Pistello, Mauro, Diotti, Roberta A., Sautto, Giuseppe A., Tarr, Alexander W., Mailland, Federico, Concas, Daniela, Burioni, Roberto, Clementi, Massimo, Mancini, Nicasio
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Viral - immunology; Antibodies, Viral - pharmacology; Cell-to-cell virus transmission; Cercopithecus aethiops; Cross Protection - immunology; Disease Models, Animal; Eye - pathology; Female; HEK293 Cells; Herpes Simplex - immunology; Herpes Simplex - prevention & control; Herpes Simplex - transmission; Herpes Simplex - virology; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - immunology; Herpesvirus 1, Human - pathogenicity; Herpesvirus 2, Human - drug effects; Herpesvirus 2, Human - immunology; Herpesvirus 2, Human - pathogenicity; HSV disseminated infection; Human antibodies; Humans; In vivo protection; Kidney - pathology; Mice; Mice, Inbred C57BL; Neutralization Tests; Vero Cells; Viral Envelope Proteins - immunology; Viral Plaque Assay; Virus Internalization - drug effects; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2017.03.028

The present study focused on inhibition of HSV-1 and -2 replication and pathogenesis in vitro and in vivo, through the selective targeting of the envelope glycoprotein D. Firstly, a human monoclonal antibody (Hu-mAb#33) was identified that could neutralise both HSV-1 and -2 at nM concentrations, including clinical isolates from patients affected by different clinical manifestations and featuring different susceptibility to acyclovir in vitro. Secondly, the potency of inhibition of both infection by cell-free viruses and cell-to-cell virus transmission was also assessed. Finally, mice receiving a single systemic injection of Hu-mAb#33 were protected from death and severe clinical manifestations following both ocular and vaginal HSV-1 and -2 lethal challenge. These results pave the way for further studies reassessing the importance of HSV entry as a novel target for therapeutic intervention and inhibition of cell-to-cell virus transmission. •HSV-1 and -2 cross-protection is conferred in vivo by a single post-infection systemic administration of a human anti-gD mAb.•Inhibition of HSV entry by this mAb also results in inhibition of cell-to-cell virus transmission.•Different molecular formats (Fab, scFv and IgG) of Hu-mAb#33 exert different anti-viral activity.•HSV-1 and -2 clinical isolates are more sensitive to mAb#33 activity compared to reference virus laboratory strains.