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

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

Abstract

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.

Citation

Clementi, N., Criscuolo, E., Cappelletti, F., Quaranta, P., Pistello, M., Diotti, R. A., Sautto, G. A., Tarr, A. W., Mailland, F., Concas, D., Burioni, R., Clementi, M., & Mancini, N. (2017). Entry inhibition of HSV-1 and -2 protects mice from viral lethal challenge. Antiviral Research, 143, https://doi.org/10.1016/j.antiviral.2017.03.028

• Journal Article Type: Article
• Acceptance Date: Mar 31, 2017
• Online Publication Date: Apr 8, 2017
• Publication Date: Jul 1, 2017
• Deposit Date: Sep 13, 2017
• Publicly Available Date: Sep 13, 2017
• Journal: Antiviral Research
• Print ISSN: 0166-3542
• Electronic ISSN: 1872-9096
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 143
• DOI: https://doi.org/10.1016/j.antiviral.2017.03.028
• Keywords: HSV disseminated infection; Cell-to-cell virus transmission; Human antibodies; In vivo protection
• Public URL: https://nottingham-repository.worktribe.com/output/967821
• Publisher URL: http://www.sciencedirect.com/science/article/pii/S0166354216307562
• Contract Date: Sep 13, 2017