Protection of nude mice by passive immunization with a type-common human recombinant monoclonal antibody against HSV.
Herpes simplex viral disease is an important cause of morbidity and mortality in man. Although the development of very effective nucleoside analogs with a high therapeutic index has greatly improved the clinical management of herpetic infections, the emergence of drug-resistant viral strains has become a cause of serious concern both because of its clinical implications and in terms of viral ecology. The present report is the first demonstration of the in vivo protective activity of a type-common human recombinant monoclonal antibody derived from a combinatorial antibody library. Athymic nude mice were infected with HSV type 1 either intracutaneously in the flank or by corneal scarification. Beside reducing morality rates when administered before infection, the antibody dramatically and significantly prolonged survival times (P < 0.0001) when administered up to 24 hr postinfection, a time when the virus had already reached the peripheral nervous system. This suggests that the antibody may act, at least in part, by interfering with axonal transport of the virus and/or with viral expression. These results indicate that human recombinant antibodies isolated by antigen selection from combinatorial libraries can be effective in vivo. Such antibodies could complement antiviral chemotherapy and represent valuable tools for the prophylaxis of infections by the herpes simplex viruses.
Sanna
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PP
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
De Logu
A
A
Williamson
R A
RA
Hom
Y L
YL
Straus
S E
SE
Bloom
F E
FE
Burton
D R
DR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology*; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D006561:Herpes Simplex / Q000276:immunology / Q000517:prevention & control*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1