Herbreteau Cécile Hélène, Jacquot Frédéric, Rith Sareth, Vacher Laurent, Nguyen Ludovic, Carbonnelle Caroline, Lotteau Vincent, Jolivet Michel, Raoul Hervé, Buchy Philippe, Saluzzo Jean-François
Fab'entech, Lyon, France.
Immunotherapy. 2014;6(6):699-708. doi: 10.2217/imt.14.40. Epub 2014 Mar 27.
There is still no specific therapy for infection with the highly pathogenic avian influenza A virus (HPAI) H5N1, which caused 39 human cases with a 64% fatality rate in 2013.
MATERIALS & METHODS: We prepared highly purified specific equine polyclonal immunoglobulin fragments (F(ab')2) against H5N1 and tested them for efficacy in vitro and with different administration schedules in H5N1-challenged BALB/c mice.
in vitro, F(ab')2 neutralized 21 different H5N1 strains from different areas, representative of 11 different clades and sub-clades and 9 years of evolution of the virus. In vivo mouse experiments identified that the most efficient administration protocol consists of five consecutive daily injections after infection; 10 mg/kg giving a 60% increase in survival.
These data demonstrate the ability of anti-H5N1 F(ab')2 to markedly reduce the mortality and morbidity associated with infection of mice with HPAI H5N1 virus, and their potential for human therapy.
对于高致病性甲型禽流感病毒(HPAI)H5N1感染,目前仍没有特效疗法,该病毒在2013年导致了39例人类感染病例,病死率达64%。
我们制备了针对H5N1的高度纯化的特异性马多克隆免疫球蛋白片段(F(ab')2),并在体外以及在感染H5N1的BALB/c小鼠中采用不同给药方案测试其疗效。
在体外,F(ab')2中和了来自不同地区的21种不同H5N1毒株,这些毒株代表了11个不同的进化枝和亚进化枝以及该病毒9年的进化历程。体内小鼠实验确定,最有效的给药方案是在感染后连续5天每日注射;10mg/kg可使存活率提高60%。
这些数据证明了抗H5N1 F(ab')2能够显著降低感染HPAI H5N1病毒的小鼠的死亡率和发病率,以及它们在人类治疗中的潜力。