Pratt Timothy S, Pincus Seth H, Hale Martha L, Moreira Andre L, Roy Chad J, Tchou-Wong Kam-Meng
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.
Exp Lung Res. 2007 Oct-Nov;33(8-9):459-81. doi: 10.1080/01902140701731805.
To investigate the effectiveness of passive antibody treatment as post-exposure therapy for ricin, we had developed an oropharyngeal aspiration model for ricin lethal challenge and antibody administration. When polyclonal anti-deglycosylated ricin A-chain antibody (dgA Ab) was administered between 1-18 hr after ricin challenge, all animals survived while delayed treatment to 24 hr resulted in 30% survival. The protective effects of dgA Ab correlated with inhibition of apoptosis in the lungs in vivo and in RAW264.7 macrophage and Jurkat T cells in vitro. In addition, ricin-induced cell cytotoxicity was inhibited by both dgA Ab and RAC18 monoclonal antibody against ricin A-chain. Administration of RAC18 monoclonal antibody at 4, 18, and 24 hr after ricin exposure resulted in 100%, 60% and 50% protection, respectively, suggesting that the therapeutic window for passive vaccination extended to at least 24 hr post-ricin lung challenge.
为了研究被动抗体治疗作为蓖麻毒素暴露后疗法的有效性，我们开发了一种用于蓖麻毒素致死性攻击和抗体给药的口咽吸入模型。当在蓖麻毒素攻击后1 - 18小时之间给予多克隆抗去糖基化蓖麻毒素A链抗体（dgA Ab）时，所有动物均存活，而将治疗延迟至24小时则导致30%的存活率。dgA Ab的保护作用与体内肺组织以及体外RAW264.7巨噬细胞和Jurkat T细胞中细胞凋亡的抑制相关。此外，dgA Ab和抗蓖麻毒素A链的RAC18单克隆抗体均抑制了蓖麻毒素诱导的细胞毒性。在蓖麻毒素暴露后4小时、18小时和24小时给予RAC18单克隆抗体分别导致100%、60%和50%的保护率，这表明被动疫苗接种的治疗窗口可延长至蓖麻毒素肺部攻击后至少24小时。
