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抗体的控释用于雌性小鼠抗生殖器疱疹的长期局部被动免疫保护

Controlled release of antibodies for long-term topical passive immunoprotection of female mice against genital herpes.

作者信息

Sherwood J K, Zeitlin L, Whaley K J, Cone R A, Saltzman M

机构信息

Department of Chemical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.

出版信息

Nat Biotechnol. 1996 Apr;14(4):468-71. doi: 10.1038/nbt0496-468.

Abstract

Current methods for sexually transmitted diseases (STD) prophylaxis, which can be disruptive and inconvenient, must be used before each act of sexual intercourse, so a method that provides protection over the course of many acts is desirable. We used a mouse model of vaginally-transmitted herpes simplex virus 2 (HSV-2) infection to test polymeric controlled-release devices for sustained passive immunoprotection. Vaginal disks were prepared by dispersing a monoclonal antibody to HSV-2 (III-174) within a matrix of poly(ethylene-co-vinyl acetate); these disks released 2 to 40 micrograms/day of antibody into buffered water. When disks were placed in the vagina, large amounts of III-174 (5 to 3,000 ng) were recovered from the vaginal fluid over the next 8 days. Mice were vaginally challenged with 10 ID50 of HSV-2 either 3 or 7 days after disk placement; no mice receiving III-174 disks became infected, while 65% of control mice receiving identical disks with nonspecific IgG did. Controlled-release disks with III-174 provided significant protection against HSV-2 infection (p < 0.005). This new technology for long-term STD prophylaxis should increase user compliance, a factor limiting the efficacy of current methods.

摘要

当前用于预防性传播疾病(STD)的方法可能会带来不便且具有干扰性,必须在每次性行为之前使用,因此,一种能在多次性行为过程中提供保护的方法是很有必要的。我们使用了阴道传播的单纯疱疹病毒2型(HSV-2)感染的小鼠模型来测试聚合物控释装置,以实现持续的被动免疫保护。通过将抗HSV-2单克隆抗体(III-174)分散在聚(乙烯-共-醋酸乙烯酯)基质中制备阴道盘;这些盘每天向缓冲水中释放2至40微克抗体。当将盘放入阴道中时,在接下来的8天内从阴道液中回收了大量的III-174(5至3000纳克)。在放置盘3天或7天后,用10个半数感染量(ID50)的HSV-2对小鼠进行阴道攻击;接受III-174盘的小鼠没有一只被感染,而接受含有非特异性IgG的相同盘的对照小鼠中有65%被感染。含有III-174的控释盘对HSV-2感染提供了显著的保护作用(p<0.005)。这种用于长期预防性传播疾病的新技术应该会提高使用者的依从性,而使用者依从性是限制当前方法有效性的一个因素。

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