title: Entry inhibition of HSV-1 and -2 protects mice from viral lethal challenge.
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.
authors.affiliation: Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy. Electronic address: clementi.nicola@hsr.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Clementi
authors.affiliation: Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Criscuolo
authors.affiliation: Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cappelletti
authors.affiliation: Department of Translational Research, University of Pisa, Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Quaranta
authors.affiliation: Department of Translational Research, University of Pisa, Pisa, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Pistello
authors.affiliation: Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy.
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Diotti
authors.affiliation: Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy.
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Sautto
authors.affiliation: School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, United Kingdom.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Tarr
authors.affiliation: Scientific Department, Polichem SA Lugano, Lugano, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Mailland
authors.affiliation: Wezen Bio AG, Fondation pour Recherches Medicales, Geneva, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Concas
authors.affiliation: Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy; Laboratory of Microbiology and Virology, San Raffaele Hospital, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Burioni
authors.affiliation: Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy; Laboratory of Microbiology and Virology, San Raffaele Hospital, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Clementi
authors.affiliation: Microbiology and Virology Unit, 'Vita-Salute San Raffaele' University, Milan, Italy; Laboratory of Microbiology and Virology, San Raffaele Hospital, Milan, Italy.
authors.forename: Nicasio
authors.initials: N
authors.lastname: Mancini
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D000914:Antibodies, Viral / Q000276:immunology / Q000494:pharmacology; D002522:Chlorocebus aethiops; D056738:Cross Protection / Q000276:immunology; D004195:Disease Models, Animal; D005123:Eye / Q000473:pathology; D005260:Female; D057809:HEK293 Cells; D006561:Herpes Simplex / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007668:Kidney / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology; D010948:Viral Plaque Assay; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1
keywords: Cell-to-cell virus transmission; HSV disseminated infection; Human antibodies; In vivo protection