Characterization of a Type-Common Human Recombinant Monoclonal Antibody to Herpes Simplex Virus with High Therapeutic Potential

Author:

De Logu Alessandro12,Williamson R. Anthony3,Rozenshteyn Roman1,Ramiro-Ibañez Fernando1,Simpson Cindy D.1,Burton Dennis R.34,Paolo Sanna Pietro1

Affiliation:

1. Departments of Neuropharmacology,1

2. Sezione di Microbiologia e Virologia, Dipartimento di Scienze Chirurgiche e Trapianti d’Organo Università di Cagliari, Cagliari, Italy2

3. Immunology,3 and

4. Molecular Biology,4 The Scripps Research Institute, La Jolla, California, and

Abstract

ABSTRACT We report the characterization of a type-common human recombinant monoclonal antibody previously isolated by antigen selection from a phage-displayed combinatorial antibody library established from a herpes simplex virus (HSV)-seropositive individual. Competition with well-characterized murine monoclonal antibodies and immunodetection of gD truncations revealed that this antibody recognizes the group Ib antigenic site of glycoprotein D, a highly conserved and protective type-common determinant. To our knowledge, this is the first human group Ib monoclonal antibody ever described. The antibody also displayed first-order neutralization kinetics and a high neutralization rate constant, was capable of completely inhibiting syncytium formation by a fusogenic strain of HSV type 1, and efficiently neutralized low-passage clinical isolates of both HSV serotypes. Taken together with our earlier observations of the in vivo antiviral activities of this human recombinant antibody in animal models of HSV infection, the present results support the high therapeutic potential of this antibody.

Publisher

American Society for Microbiology

Subject

Microbiology (medical)

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