Characterization of a type-common human recombinant monoclonal antibody to herpes simplex virus with high therapeutic potential.
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.
Departments of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA.
A
A
De Logu
R A
RA
Williamson
R
R
Rozenshteyn
F
F
Ramiro-Ibañez
C D
CD
Simpson
D R
DR
Burton
P P
PP
Sanna
D000818:Animals; D000911:Antibodies, Monoclonal / Q000145:classification / Q000235:genetics / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D000956:Antigens, Viral / Q000235:genetics; D002522:Chlorocebus aethiops; D003588:Cytopathogenic Effect, Viral / Q000276:immunology; D018604:Epitope Mapping; D006561:Herpes Simplex / Q000628:therapy; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D018139:Simplexvirus / Q000276:immunology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1