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 mo rtality in man, Although the development of very effective nucleoside analogs with a high therapeutic index has greatly improved the clinica l management of herpetic infections, the emergence of drug-resistant v iral strains has become a cause of serious concern both because of its clinical implications and in terms of viral ecology. The present repo rt is the first demonstration of the in vivo protective activity of a type-common human recombinant monoclonal antibody derived from a combi natorial antibody library. Athymic nude mice were infected with HSV ty pe 1 either intracutaneously in the flank or by corneal scarification. Beside reducing mortality rates when administered before infection, t he antibody dramatically and significantly prolonged survival times (P < 0.0001) when administered up to 24 hr postinfection, a time when th e virus had already reached the peripheral nervous system. This sugges ts that the antibody may act, at least in parr, by interfering with ax onal transport of the virus and/or with viral expression. These result s indicate that human recombinant antibodies isolated by antigen selec tion from combinatorial libraries can be effective in vivo. Such antib odies could complement antiviral chemotherapy and represent valuable t ools for the prophylaxis of infections by the herpes simplex viruses. (C) 1996 Academic Press, Inc.