Sanna P P, De Logu A, Williamson R A, Hom Y L, Straus S E, Bloom F E, Burton D R
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
Virology. 1996 Jan 1;215(1):101-6. doi: 10.1006/viro.1996.0011.
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.
单纯疱疹病毒病是人类发病和死亡的重要原因。尽管具有高治疗指数的非常有效的核苷类似物的开发极大地改善了疱疹感染的临床管理，但耐药病毒株的出现已成为一个严重关切的问题，这既是因为其临床影响，也是就病毒生态学而言。本报告首次证明了源自组合抗体库的一种通用型人重组单克隆抗体的体内保护活性。无胸腺裸鼠通过在胁腹皮内注射或角膜划痕感染1型单纯疱疹病毒。该抗体在感染前给药时除了降低死亡率外，在感染后长达24小时给药时（此时病毒已到达外周神经系统）显著延长了存活时间（P < 0.0001）。这表明该抗体可能至少部分通过干扰病毒的轴突运输和/或病毒表达而起作用。这些结果表明，通过从组合文库中进行抗原选择分离出的人重组抗体在体内可能有效。此类抗体可补充抗病毒化疗，并代表预防单纯疱疹病毒感染的有价值工具。
